INSOMNIA A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R EFERENCES
J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS
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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright ©2004 by ICON Group International, Inc. Copyright ©2004 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1
Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Insomnia: 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: 0-597-83992-1 1. Insomnia-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:
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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 insomnia. 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 INSOMNIA ................................................................................................. 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Insomnia ..................................................................................... 12 E-Journals: PubMed Central ....................................................................................................... 68 The National Library of Medicine: PubMed ................................................................................ 68 CHAPTER 2. NUTRITION AND INSOMNIA ..................................................................................... 113 Overview.................................................................................................................................... 113 Finding Nutrition Studies on Insomnia .................................................................................... 113 Federal Resources on Nutrition ................................................................................................. 118 Additional Web Resources ......................................................................................................... 118 CHAPTER 3. ALTERNATIVE MEDICINE AND INSOMNIA ............................................................... 121 Overview.................................................................................................................................... 121 National Center for Complementary and Alternative Medicine................................................ 121 Additional Web Resources ......................................................................................................... 141 General References ..................................................................................................................... 161 CHAPTER 4. DISSERTATIONS ON INSOMNIA ................................................................................. 163 Overview.................................................................................................................................... 163 Dissertations on Insomnia ......................................................................................................... 163 Keeping Current ........................................................................................................................ 164 CHAPTER 5. CLINICAL TRIALS AND INSOMNIA ............................................................................ 165 Overview.................................................................................................................................... 165 Recent Trials on Insomnia ......................................................................................................... 165 Keeping Current on Clinical Trials ........................................................................................... 167 CHAPTER 6. PATENTS ON INSOMNIA ............................................................................................ 169 Overview.................................................................................................................................... 169 Patents on Insomnia .................................................................................................................. 169 Patent Applications on Insomnia............................................................................................... 189 Keeping Current ........................................................................................................................ 198 CHAPTER 7. BOOKS ON INSOMNIA ............................................................................................... 199 Overview.................................................................................................................................... 199 Book Summaries: Federal Agencies............................................................................................ 199 Book Summaries: Online Booksellers......................................................................................... 203 The National Library of Medicine Book Index ........................................................................... 208 Chapters on Insomnia ................................................................................................................ 210 CHAPTER 8. MULTIMEDIA ON INSOMNIA ..................................................................................... 213 Overview.................................................................................................................................... 213 Video Recordings ....................................................................................................................... 213 Bibliography: Multimedia on Insomnia ..................................................................................... 214 CHAPTER 9. PERIODICALS AND NEWS ON INSOMNIA .................................................................. 215 Overview.................................................................................................................................... 215 News Services and Press Releases.............................................................................................. 215 Newsletter Articles .................................................................................................................... 219 Academic Periodicals covering Insomnia................................................................................... 220 CHAPTER 10. RESEARCHING MEDICATIONS................................................................................. 221 Overview.................................................................................................................................... 221 U.S. Pharmacopeia..................................................................................................................... 221 Commercial Databases ............................................................................................................... 222 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 227 Overview.................................................................................................................................... 227
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NIH Guidelines.......................................................................................................................... 227 NIH Databases........................................................................................................................... 229 Other Commercial Databases..................................................................................................... 231 The Genome Project and Insomnia ............................................................................................ 231 APPENDIX B. PATIENT RESOURCES ............................................................................................... 235 Overview.................................................................................................................................... 235 Patient Guideline Sources.......................................................................................................... 235 Finding Associations.................................................................................................................. 242 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 245 Overview.................................................................................................................................... 245 Preparation................................................................................................................................. 245 Finding a Local Medical Library................................................................................................ 245 Medical Libraries in the U.S. and Canada ................................................................................. 245 ONLINE GLOSSARIES................................................................................................................ 251 Online Dictionary Directories ................................................................................................... 254 INSOMNIA DICTIONARY......................................................................................................... 255 INDEX .............................................................................................................................................. 331
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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 insomnia 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 insomnia, 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 insomnia, 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 insomnia. 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 insomnia, 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 insomnia. 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 INSOMNIA Overview In this chapter, we will show you how to locate peer-reviewed references and studies on insomnia.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and insomnia, 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 “insomnia” (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: •
Pills! Chills! Thrills! Spills! Source: POZ. p. 54-59. September 2000. Contact: Available from POZ Publishing. P.O. Box 417, Mt. Morris, IL 61054. (800) 9732376. Canada, Mexico and overseas call (815) 734-4151. E-mail:
[email protected]. Website: www.poz.com. Summary: Drugs that fight HIV and opportunistic infections are lengthening the life spans of people with HIV, but the list of troubling side effects is also growing. This article reports on a variety of drug related complications and side effects that are common in people taking HIV medications. The author stresses the importance of staying in touch with one's body in order to better monitor side effects and problems as they arise. Communication with one's health care provider is also noted as an essential
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component to success. The author reminds readers that it often takes 2 to 6 weeks to adjust to a new medication, but that complications can also arise even after a year or two on a seemingly beneficial drug combination. Regardless of the specific symptom, it is vital to always seek a full diagnosis of the possible contributing causes. The author then discusses each symptom in turn, including appetite loss, body distortions (bumps and lumps), bone death, diarrhea, fatigue, gas and bloating, hair loss, insulin resistance and diabetes, kidney stones, muscle aches and pains (myopathy), nausea, neuropathy (nerve damage), anxiety and depression, insomnia, pancreatitis, and skin disorders (rashes). In each section, the author offers commonsense approaches to coping with the symptom and some possible information regarding the cause (which drug or drugs might be responsible). One sidebar reviews the expected laboratory numbers for liver function tests, kidney function tests, blood cells, and cardiovascular monitoring tests. 6 figures. •
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 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.
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Sleep Disorders: A Common Problem Among Kidney Patients? Source: For Patients Only. 8(1): 8-10, 24. January-February 1995. Contact: Available from Contemporary Dialysis, Inc. 6300 Variel Avenue, Suite I, Woodland Hills, CA 91367. Summary: In this article, the author provides readers with information about an oftenencountered, but little-discussed complication of dialysis, insomnia. Topics include the adequacy of dialysis and its impact on the sleep habits of patients; restless leg syndrome (RLS) and the role of peripheral neuropathy in its development; the use of Sinemet to treat RLS; using conventional sleep aids, including Ambien; the use of muscle relaxants, or benzodiazepines, for milder forms of RLS; psychological sleep disturbances; and adjunctive therapies, including Qigong, biofeedback, and meditation. The author encourages readers to become more self-aware and to participate as an active member of their own health care team. The article includes a short list of references and organizations that may provide additional information about sleep disorders and their therapy.
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Weird Workout Reactions Source: Fitness. p.61,63,65. June 1998. Summary: Parlapiano explains how 9 symptoms may be related to exercise. The 9 are: dizziness, insomnia, frequent yeast infections, loss of appetite, breast pain, tingling feet, irregular bleeding, headaches, and stomach cramps. For each, Parlapiano interviewed a physician or exercise physiologist, who explains how the symptom may be related to exercise and how to treat it. Some causes of these symptoms are: overtraining; exercising too soon after eating; dehydration; fallen arches; and exercising too soon before bed.
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Causes and Treatment of Behavioral Changes Source: Consultant. 28(1): 43-45, 48. January 1988. Summary: This article describes Alzheimer's disease as an increasingly common management concern for primary care physicians. Although little can be done for the primary symptoms of the dementing process, the secondary behavioral complications of this illness may be amenable to behavioral or pharmacologic manipulation. Agitation may be responsive to environmental or psychosocial intervention. Treatment with low doses of antidepressants can improve depressive symptoms. Mild anxiety is best treated with emotional support from the family and caregiver. Benzodiazepines can be used with caution. Insomnia can be reduced by encouraging a routine that prevents daytime napping and keeping the patient busy during the day. Pharmacotherapy for disturbed sleep often causes more harm than good and should be avoided if possible. 3 references. (AA-M).
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Sleep and Dialysis: A Research-Based Review of the Literature Source: ANNA Journal. American Nephrology Nurses Association Journal. 24(6): 626641. December 1997. Contact: Available from American Nephrology Nurses Association. Box 56, East Holly Avenue, Pitman, NJ 08071. (609) 256-2320. Summary: This article reviews the interrelationship of sleep and dialysis. Textbook descriptions of dialysis patients have long included features of insomnia, day-night reversal, and disturbed sleep. More recently, a very high prevalence of subjective sleep complaints and specific primary sleep disorders such as sleep apnea syndrome, periodic leg movement disorder, and restless legs syndrome have been documented in this population. The author of this article assists dialysis nurses in their efforts to better understand the sleep alterations experienced by their patients. Topics include the prevalence and importance of sleep complaints in dialysis patients; subjective features and related factors; polysomnographic features; and contributing factors. The author concludes that, despite the prolongation of life by dialysis and improved overall medical management, sleep disturbances remain a major problem for patients and may contribute to the low rehabilitation rate seen in the end-stage renal disease (ESRD) population. One lengthy chart (four pages of the article) summarizes the authors, purpose, methods, subjects, results, and conclusions of sleep research studies in dialysis patients. Another chart provides a glossary of related terms. 2 tables. 79 references. (AAM).
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Memories are made of Folic Acid, B1, B3, NA, and ZN Source: Lifeline. 10(1): 3. Winter 1992.
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Contact: Available from Celiac Sprue Association/USA, Inc. P.O. Box 31700, Omaha, NE 68131. (402) 558-0600. Summary: This brief newsletter article explores the relationship between good nutrition and cognitive function, with an emphasis on the impact of celiac disease in this area. Topics include nutrition and memory; vitamins and intelligence; and research on these topics. The article concludes with a list of some common symptoms and the vitamins and minerals reported to be related. Symptoms listed include apathy, confusion, depression, dry eye, fatigue, insomnia, irritability, muscle problems, nervousness, night blindness, numbness of limbs, poor appetite, poor coordination, poor memory, rapid pulse, sensitivity to light, and sore tongue. 2 references. •
Behavioral Treatment of Sleep Disturbance in Elderly Dementia Caregivers Source: Clinical Gerontologist. 17(2): 35-50. 1996. Summary: This journal article describes a behavioral treatment for sleep disturbances in older family caregivers of people with dementia. Four spouses of people with probable or possible Alzheimer's disease (AD) were asked to participate in a behavioral intervention for caregiver insomnia. All of the participants reported sleep problems an average of three or more nights per week. The treatment consisted of six 90-minute group sessions held once a week. Participants received information about managing behavior problems associated with AD and instruction in sleep hygiene, stimulus control, sleep compression, and relaxation techniques. The sleep hygiene instructions included telling the caregivers not to drink caffeinated beverages in the evening and to avoid naps after 1:00 p.m. The stimulus control instructions included telling the caregivers to establish a bedtime routine, to not read in bed and, if unable to fall asleep within 15 minutes, to leave the bedroom and engage in a quiet activity until they became drowsy. Data from the caregivers' daily sleep diaries suggested that they were able to improve their time to falling asleep, number of nighttime awakenings, hours of nightly sleep, and sleep efficiency. The treatment also appeared to reduce feelings of depression and burden in some caregivers. The authors conclude that the behavioral intervention may be an effective treatment for sleep problems in older caregivers of people with dementia. 4 figures, 28 references.
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Psychotic Symptoms in Parkinson's Disease Patients With Dementia Source: Journal of the American Geriatrics Society. 44(3): 296-299. March 1996. Summary: This journal article describes a study of the prevalence and correlates of psychotic symptoms in patients with Parkinson's disease (PD) and dementia. Data for 101 PD patients with dementia were obtained from the pooled database of the nine State of California Alzheimer's Disease Diagnostic and Treatment Centers. Most of the patients (92 percent) had severe PD symptoms. Thirty-six patients (35.6 percent) had psychosis, defined as the presence of hallucinations and/or delusions; 19 patients had both hallucinations and delusions, 10 had hallucinations only, and 7 had delusions only. The psychotic and non-psychotic patients were similar demographically, but the psychotic patients had significantly more insomnia, confusion, agitation, personality changes, self-care problems, and greater cognitive and functional impairment. In a logistic regression model, the patient's age, duration of dementia, and level of cognitive impairment were significant predictors of psychosis. The authors conclude that psychotic symptoms in PD with dementia is associated with major behavioral, cognitive, and functional problems. 1 table, 28 references.
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Effect of Melatonin in Selected Populations of Sleep-Disturbed Patients Source: Biological Signals and Receptors. 8: 126-131. 1999. Summary: This journal article describes two studies of the effects of melatonin in selected populations of patients with sleep disturbances. In one study, 22 patients patients with sleep disturbances only, 9 with sleep disturbances and signs of depression, and 10 with sleep disturbances and dementia received 3 mg of melatonin by mouth at bedtime for 21 days. After two to three days of treatment, melatonin significantly improved sleep quality and decreased the number of awakening episodes in patients with sleep disturbances alone or associated with depression. Estimates of next-day alertness improved significantly only in patients with primary insomnia. Agitated behavior at night (sundowning) descreased significantly in the patients with dementia. In the second, retrospective study, 14 patients with Alzheimer's disease (AD) received 9 mg of melatonin daily for 22 to 35 months. Sleep quality was significantly improved, although there was no change in neuropsychological performance. The authors conclude that melatonin may be useful for treating sleep disturbances in older insomniacs and AD patients. 1 figure, 2 tables, 18 references.
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Surgery and the Patient With Alzheimer's Disease Source: Geriatric Nursing. 9(4): 227-229. July-August 1988. Summary: This journal article discusses preoperative precautions and education for patients with Alzheimer's disease. Memory loss may make medical history taking difficult, therefore, a family member or guardian should be consulted. Behavioral changes such as aggressiveness, anxiety, depression, agitation, insomnia, and paranoia, may necessitate the use of antipsychotics, tranquilizers or antidepressants. However, drugs should be administered with extreme caution and in reduced dosages since Alzheimer's disease patients are extremely sensitive to medications. Use of preoperative medication in patients with advanced Alzheimer's disease should only be used for analgesia or agitation. Preoperative education for both the patient and family is essential in reducing confusion and anxiety and providing understanding and support. Preoperative instructions should be written for reinforcement. Surgery for most patients with Alzheimer's disease is performed under general anesthesia. Since delayed recovery from anesthesia is common, prolonged observation will be required in the recovery room and patient care unit. Nurses should instruct both patients and family members in any continued postoperative care to be followed at home, including drug therapy. As reinforcement, patients should receive concise, written instructions. With supportive assistance and an understanding of the behaviors associated with Alzheimer's disease, nurses can help patients through a surgical procedure.
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Managing Early Alzheimer's Disease Source: Patient Care. 25(18): 44-73. November 15, 1991. Summary: This journal article discusses the primary care physician's role in the management of patients in the early stages of Alzheimer's disease. The authors emphasize that the role of the primary care physician goes beyond medical care and includes providing ongoing support and education to patients with Alzheimer's disease and their families. Advice is given about how to talk with patients and their families and how to convey information about their condition. Practical suggestions are provided to help caregivers deal with common behavior problems such as agitation, catastrophic reactions, eating or bathing difficulties, incontinence, insomnia, repeated questioning, shadowing the caregiver, sundowning, and wandering. Additional points discussed
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include: the use of psychotropic drugs for managing anxiety and aggression; conducting mental and functional assessments; and ongoing medical care to prevent iatrogenic disease, detect intercurrent illness, manage preexisting medical conditions, and provide routine preventive care. The article also provides some general guidelines for caregivers and tips on communicating with a relative with Alzheimer's disease. 22 references. •
Effects of Triazolam on Sleep, Daytime Sleepiness, and Morning Stiffness in Patients With Rheumatoid Arthritis Source: Journal of Rheumatology. 23(2):245-252; 1996. Summary: This journal article for health professionals describes a double blind crossover study that evaluated the effects of triazolam upon insomnia and daytime sleepiness in patients with rheumatoid arthritis (RA). Triazolam or placebo was administered during two 7-night periods to 15 patients with RA. Polysomnographic recordings were conducted on the last two nights of each condition, and multiple sleep latency tests and mood and arthritis assessments were performed during the intervening day in each condition. Results indicate that, in the triazolam condition, total sleep time was increased, daytime sleepiness was reduced, and the duration and severity of morning stiffness were decreased compared to the placebo condition. Objective measures of sleep fragmentation were unchanged. Clinical arthritis assessments were similar during both conditions. Possible explanations for these results are presented. Results suggest judicious use of short acting hypnotics or other therapies that would improve sleep may offer some relief from sleepiness and morning stiffness associated with RA. 32 references, 2 figures, and 6 tables. (AA-M).
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Nobel Prize to Stanley Prusiner for Prion Discovery Source: JAMA. Journal of the American Medical Association. 278(18): 1479. November 12, 1997. Summary: This journal article highlights Stanley Prusiner's 1997 Nobel Prize-winning work on the role of prions in brain diseases. Dr. Prusiner found that a novel class of infectious proteins, called prions, may be responsible for a variety of fatal neurodegenerative diseases such as kuru, Creutzfeldt-Jakob disease (CJD), GertsmannStraussler-Scheinker (GSS) disease, and fatal familial insomnia in humans; and transmissible spongiform encephalopathies such as scrapie and mad cow disease in animals. Prions are a type of protein normally found in humans and other organisms. Dr. Prusiner's research also provided evidence that an abnormal prion protein may play a role in inherited forms of GSS disease and CJD. In announcing the 1997 award, the Nobel committee said that Dr. Prusiner's work may lead to a better understanding of the pathogenesis of more common dementias such as Alzheimer's disease.
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Oral Lichen Planus: Patient Profile, Disease Progression and Treatment Responses Source: Journal of the American Dental Association. JADA. 132(7): 901-909. July 2001. Summary: This journal article provides health professionals with information on a retrospective, descriptive study that investigated the characteristics of patients with oral lichen planus (OLP), disease progression, and treatment responses. The study included 229 patients with OLP who were seen in the oral medicine clinic at the University of California, San Francisco, between September 1996 and August 2000, for the first time or for a follow up visit. Signs and symptoms at various clinic visits were quantified. Responses to treatment and disease progression were determined by comparing scores with baseline scores. The study found that the mean age at onset of the disease was 55
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years, and 154 of the patients were female. Symptoms generally correlated directly with the severity of OLP forms, which ranged from reticular to erosive. Corticosteroids were effective in reducing symptoms, healing ulcers, and reducing erythema. Among the patients treated with prednisone at the first clinic visit, the most common reported side effects were insomnia, mood swings, fatigue, and water retention. At last follow up, 65 percent of the patients had the same type of OLP seen initially or the disease had progressed to a more severe type, while 35 percent of patients had the less severe forms than that seen at the initial visit. Four patients developed oral squamous cell carcinoma during the follow up period. The article concludes that, although the response of patients with OLP to a short course of systemic corticosteroids is often remarkable, symptoms and signs tend to recur after this treatment. Clinicians need to monitor patients for side effects, including oral candidiasis and possible malignant transformation. 3 figures, 3 tables, and 13 references. (AA-M). •
Delusions and Behavioral Disturbances in Cognitively Impaired Elderly Persons Source: Journal of the American Geriatrics Society. 40(8): 768-773. August 1992. Summary: This journal article reports a study that found that delusions in persons with Alzheimer's disease or other dementia are associated with a variety of behavioral problems. The study utilized a retrospective review of the medical records of 114 outpatients with diagnoses of either Alzheimer's disease, multi-infarct dementia, or a mix of the two. Delusions were reported for 25.5 percent of the patients. Several behavioral disturbances were more common in delusional than in nondelusional patients, including agitation, angry or hostile outbursts, urinary incontinence, wandering or pacing, and insomnia. Delusional and nondelusional patients had similar cognitive function as measured by the Mini-Mental State Exam, although there was a statistically borderline tendency for delusions to occur more often in patients in the midrange of cognitive impairment. 29 references.
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Delusions in Dementia: A Review Source: Journal of Neuropsychiatry. 3(2): 121-130. Spring 1991. Summary: This journal article reviews delusions that complicate dementia. According to the author, delusions, hallucinations, agitation, wandering, insomnia, and noisiness must be studied separately to understand their physiopathology and nature in order to effectively manage dementia. Six areas pertaining to delusions in dementia are reviewed: nosology, phenomenology, epidemiology, clinical characteristics and correlations (including cognition, depression, and sensory deficits), treatment with antipsychotic medications, course and prognosis. Reports of studies dating as far back as 1955 were reviewed. The author notes that the study of one particular complication of dementia, delusion, illustrates current deficiencies of knowledge in some areas. The author asserts that postmortem studies are needed to understand the mechanisms that underlie psychotic symptoms in dementia. 90 references.
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Pharmacotherapy for Long-Term Care Residents With Dementia-Associated Behavioral Disturbance Source: Journal of Psychosocial Nursing. 36(2): 27-31. 1998. Summary: This journal article summarizes Federal guidelines for benzodiazepine and antipsychotic drug use in long-term care residents with dementia. The Nursing Home Reform Amendments of the Omnibus Budget Reconciliation Act of 1987 (OBRA 87) have resulted in close supervision of the use of unnecessary drugs for residents in
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Medicare and Medicaid certified nursing homes. They require documenting the behavioral indication for psychotropic drugs, monitoring their safety and efficacy, drug holidays, behavioral management instead of drugs when possible, and systematic dose reductions unless clinically contraindicated. Long-acting benzodiazepines generally are not recommended for use in older patients. Short-acting benzodiazepines may be used for anxiety, insomnia, and dementia-associated agitated states that represent a danger to the patient or others. Antipsychotics may be used for dementia with psychotic features, continuous crying or screaming that impairs functional status, and dangerous behavior. 3 tables, 14 references. •
Official Guidelines for the Initial Assessment and Treatment of Alzheimer's Disease Source: Alzheimer's Research. 3(6): 227-234. December 1997. Summary: This journal article summarizes two published guidelines for the assessment and treatment of Alzheimer's disease (AD). The guideline for assessment, published in 1996 by the Agency for Health Care Policy and Research (AHCPR), focuses on triggers that might signal the presence of dementia. The guideline for treatment, published in 1997 by the American Psychiatric Association, addresses the treatment of a broad spectrum of cognitive, functional, and behavioral symptoms. AHCPR triggers that would require a physician to investigate for possible dementia include difficulty with any of the following: learning new information, complex tasks, reasoning, spatial judgment, language, and controlling behavior. When one of these triggers is present, the initial assessment should include a brief cognitive rating scale and an informant-based measure of functional performance. It is noted that a differential diagnosis of dementia first should rule out delirium and general medical conditions, and that a psychiatric assessment should be done for substance abuse, medication side effects, malingering, pseudodementia of depression, and age-related cognitive decline. Neurological conditions, including vascular dementia and Parkinson's disease, should be considered. Known risk factors for AD are mentioned, such as age, female gender, and a family history of dementia. Treatment guidelines for reversible dementias, delirium, depression, cognitive deficits in AD, psychosis, agitation, and insomnia are reviewed. Also highlighted are treatment with cholinesterase inhibitors, psychosocial therapies, and safety issues. Research needs are suggested for each area of assessment and treatment. 10 references.
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Expert Consensus Guidelines: Treatment of Agitation in Older Persons with Dementia Source: New York, NY: McGraw-Hill Healthcare Information Programs. March 1998. 88 p. Contact: McGraw-Hill Healthcare Information Programs, Two Penn Plaza, 5th floor. New York, NY 10121. (212) 904-6880; FAX: (212) 904-2506. Website: www.psychguides.com. PRICE: free online access. Summary: This Postgraduate Medicine Special Report presents practice guidelines for the treatment of agitation in older people with dementia. Intended for clinicians, it includes recommendations for the assessment of agitation in dementia, overall management strategies, the selection of environmental interventions, and the selection of medications for specific syndromes of agitation (delirium, psychosis, depression, anxiety, insomnia, sundowning, aggression or anger, and prominent pain). Other recommendations cover management of an inadequate response to medication, long term treatment issues (including long term safety and the decision to taper medication),
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the selection of specific medications within different classes of drugs, dose and side effects, and safety and tolerability. This document also provides a guide for families and caregivers, survey results, and a clinician feedback form. •
Depression in the Agitated, Demented Elderly Source: Nursing Home Medicine. 3(10): 243-247. October 1995. Summary: This study sought a possible link between agitated behavior in older people with dementia who were residing in two nursing homes and the possible presence of depression. Researchers first acquired baseline data for 20 treatment group and 20 control group patients, then administered an antidepressant (fluoxetine at 20 mg daily) to those in the treatment group for a period of 6 weeks. Several residents also received 25 milligrams of trazodone to enhance the effects of fluoxetine and reduce severe cases of insomnia. Researchers monitored all residents for signs of untoward effects. Statistical analysis indicates that agitation and noisemaking behaviors in nursing facility residents with dementia show marked improvement after the intervention, although no statistically significant posttest difference was observed between the treatment and control groups. These two groups were essentially matched with regard to other variables. Cognitive scores did not change significantly between pretest and posttest measures. The authors indicate that, while the study concludes that agitated older people with dementia can be effectively treated with antidepressants, the results are not statistically significant because of the sample size and other factors. 2 figures, 2 tables. (AA-M).
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Human Transmissible Spongiform Encephalopathies (TSEs): Implications for Dental Practitioners Source: British Dental Journal. 188(8): 432-436. April 22, 2000. Contact: Available from Stockton Press. Houndmills, Basingstoke, Hampshire, RG21 6XS, United Kingdom. E-mail:
[email protected]. Summary: Transmissible spongiform encephalopathies (TSEs) are rare, fatal degenerative brain diseases which affect humans and certain animals, and are caused by inheritance or acquisition of prions (PrPs). TSEs are characterized by the appearance of microscopic vacuoles within the grey matter of the brain, giving a spongelike appearance. Inherited TSEs include Fatal Familial Insomnia (FFI), GerstmannStraussler-Scheinker syndrome (GSS), and other less well clinically characterized disorders, while the human infective TSEs include sporadic, iatrogenic, and variant Creutzfeldt-Jakob disease (vCJD). The causative prions are found especially in neural tissues and spinal fluid, and in the case of vCJD, in lymphoreticular tissue. Available epidemiological evidence suggests that normal social or routine clinical contact with affected patients does not present a risk to health care workers, relatives or the community. Isolation of patients is not considered necessary. Nevertheless, as the prions are resistant to conventional chemical, irradiation, and heat sterilization methods, highly specific cross infection control measures are required for the dental management of patients with, or at notable risk, of TSE. This article reviews current knowledge of the clinical consequences of prion disease. The authors provide information regarding necessary changes to the cross infection routine when managing patients infected, or at risk of, prion disease. 2 tables. 48 references.
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Insomnia
Federally Funded Research on Insomnia The U.S. Government supports a variety of research studies relating to insomnia. 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 insomnia. 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 insomnia. The following is typical of the type of information found when searching the CRISP database for insomnia: •
Project Title: "EXCERSISE: A COUNTERMEASURE FOR SLEEP LOSS IN OLDER ADULTS" Principal Investigator & Institution: Zee, Phyllis C.; Professor; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2003; Project Start 01-DEC-2002; Project End 30-NOV-2007 Summary: The prevalence of chronic insomnia increases with age. Recent findings demonstrate that in addition to its detrimental effects on cognition and performance, sleep loss also has a negative impact on health, that is similar to age-related changes in metabolic, cardiovascular and immune measures of health. Despite the important medical and social consequences of chronic sleep loss that accompany the aging process, there is a paucity of safe and effective treatment strategies for the elderly. The chronic nature of the sleep problems, coupled with the side effects of hypnotic medications, limit the usefulness of pharmacological approaches for the treatment of insomnia in this older population. Therefore, there is a need to develop alternative, safe and effective approaches for the management of insomnia in older adults. Recent findings indicate that exercise can improve sleep quality in older adults. The goal of the proposed research is to determine the ability of exercise to improve sleep, health, daytime performance and overall quality of life in older adults with insomnia. Specific aim 1 is to determine the effects of exercise and sleep hygiene education on objective and subjective measures of sleep quality, sleep quantity, circadian rhythms, daytime performance, mood and quality of life in older adults with insomnia. These objective and subjective measures will be taken during a 3-day admission to the clinical research center before and after a 16- week aerobic exercise program (3-4 sessions per week). The same measures will be taken in a control group before and after a 16-week sleep hygiene education intervention. Specific aim 2 is to determine the effects of the aerobic exercise and improvements in sleep quality and quantity on measures of health. Measurements of metabolic, endocrine, cardiovascular, as well as other biomarkers of aging such as bone turnover, autonomic and immune parameters (IL-6, TNF-alpha and C-reactive protein) will be taken before and after the 16 week exercise intervention or sleep hygiene
2 Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).
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education intervention. The proposed studies will not only determine whether exercise is an effective approach for the management of insomnia in the elderly, but will also improve our understanding of the relationship between sleep and health in older adults. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: A PHARMACOKINETIC STUDY OF A BOTANICAL EXTRACT Principal Investigator & Institution: Goldblum, Ronald; Ancile Pharmaceuticals, Inc. 9381 Judicial Dr, Ste 160 San Diego, Ca 92121 Timing: Fiscal Year 2001; Project Start 17-SEP-2001; Project End 31-AUG-2002 Summary: (provided by applicant): A new approach is proposed for conducting pharmacokinetic studies of a pharmacologically active botanical extract containing mixtures of several classes of active and inactive compounds. We are currently developing the botanical extract as a botanical drug under an allowed Investigational New Drug (IND) by the FDA. We have identified key marker compounds for PK studies based on relevant biological activity and relative abundance in the extract. We propose to develop and validate a sensitive and accurate analytical method for quantitation of the marker compounds from plasma matrix in Phase I. Development of these methods will ultimately generate a robust approach for conducting routine GLP PK studies in animals and humans, which will be the subject of Phase II. The PK studies in human will provide new information, which will be used for NDA approval of the botanical drug as an effective treatment of insomnia, a condition with a large unmet medical need for effective and safe therapeutics with a low adverse effect profile. Successful completion of the long-range goals also will enable development of unique formulations and selection of dose regimen in elderly populations. PROPOSED COMMERCIAL APPLICATION: This project will support the development, under IND, of an important new class of drugs, the Botanical Drug Product. The botanical extract, which is the subject of this study, will be developed as an effective and safe new therapeutic for insomnia, a condition where currently 95% of those affected by the disease are not currently taking prescription medication. The botanical extract we will develop as a new drug has a favorable profile relative to the "ideal" drug for treatment of this condition. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ACUPUNCTURE DIAGNOSIS AND TREATMENT OF DSM-IV PTSD Principal Investigator & Institution: Hollifield, Michael A.; Psychiatry; University of New Mexico Albuquerque Controller's Office Albuquerque, Nm 87131 Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 31-MAY-2004 Summary: (provided by applicant): This pilot study's aims are to develop a working diagnostic and treatment model of Posttraumatic Stress Disorder (PTSD) within a Traditional Chinese Medicine (TCM) paradigm, and to evaluate the acceptability and potential benefit of an acupuncture approach for the treatment of PTSD symptoms. Specifically, we will evaluate: 1) the TCM diagnostic differentiation patterns of people who have PTSD as defined by the Diagnostic and Statistical Manual, 4th edition; 2) if an acupuncture treatment approach is acceptable to people with PTSD, measured by treatment completion rate and satisfaction; and 3) if an acupuncture treatment approach is associated with a reduction in PTSD symptoms that is comparable to the treatment effect of a standard Cognitive-Behavioral Therapy (CBT) approach and better than no treatment. Because symptoms of depression, insomnia and pain are often associated with PTSD, we will also evaluate the potential benefit of an acupuncture approach on depression, insomnia and pain symptoms in people with PTSD. Analyses: A description
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of the TCM diagnoses for people with PTSD will be offered. Treatment completion rates between groups will be analyzed with Chi-square, and a continuous measure of satisfaction between groups will be analyzed with ANOVA on a single post-treatment measure. A group by time repeated measures ANOVA will be conducted to determine the relative effects of the Acupuncture vs. the CBT vs. the Wait-List condition, and will be reported in terms of both significance and effect sizes (Cohen's d). Significance: This pilot project will allow TCM practitioners to have a logical and empirical approach to TCM diagnosis and treatment of people who might be referred with PTSD. Further, this study will provide preliminary data about the acceptability and potential benefit of an acupuncture approach in people with PTSD symptoms. These data will be significant because: 1) there are no empirical data or consensus paradigms of a TCM acupuncture approach for the diagnosis and treatment of PTSD; and 2) these preliminary data should encourage higher powered randomized clinical trials about the effectiveness of acupuncture in PTSD and/or related anxiety disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ACUPUNCTURE FOR HOT FLASHES IN PROSTATE CANCER PATIENTS Principal Investigator & Institution: Beer, Tomasz M.; Associate Professor; Medicine; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2003; Project Start 14-JUL-2003; Project End 30-JUN-2005 Summary: (provided by applicant): Up to 80% of men treated with androgen deprivation for prostate cancer suffer from hot flashes. Insomnia, fatigue, and irritability are often associated with hot flashes and adversely affect the quality of life for these patients. Several pharmacologic interventions can reduce hot flash frequency and intensity but have the potential for adverse effects. Acupuncture, a 23 centuries-old treatment modality, has been reported to substantially reduce hot flash frequency in 7 men treated with androgen deprivation for prostate cancer in Sweden. The study proposed here will apply validated methodology to assess the impact of acupuncture on hot flash frequency and intensity as well as hot flash related quality of life in an adequately powered phase Ii study. To extend current understanding of the physiologic changes associated with hot flashes and with acupuncture, the impact of acupuncture on serotonin and its metabolites, metabolites of brain norepinephrine, and circulating calcitonin gene-related peptide (CGRP) will be evaluated. All three of these systems have been implicated in the pathophysiology of thermoregulatory instability associated with hot flashes. Serotonin and norepinephrine are amongst the targets of western pharmacologic treatment for hot flashes. Preliminary data suggest that acupuncture may mediate changes in circulating serotonin and CGRP. Promising results in this pilot trial will lead to randomized studies of acupuncture compared to pharmacologic therapy and pilot studies of acupuncture combined with western treatment. The overall goal is to provide prostate cancer patients an effective, low toxicity, non-pharmacologic treatment modality for hot flashes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: AGING WELL, SLEEPING EFFICIENTLY: INTERVENTION STUDIES Principal Investigator & Institution: Monk, Timothy H.; Professor; Psychiatry; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2008
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Summary: (provided by applicant): The overall aim of this program project ("AgeWise") is to determine whether the lives, health and well-being of normal elderly people can be improved by behavioral interventions designed to enhance their sleep. Most seniors are faced with aspects of their everyday lives such as bereavement, the need to care for an ailing spouse, insomnia related to physical ill-health and progression into the final years of life; all of which can present challenges both to their sleep, and to their health, wellbeing, mood and ability to function. There are three cores: Administration and Subject Recruitment (Monk), Data Collection (Buysse), and Data Analysis (Mazumdar), and five component projects (see below) all using a shared battery of measures (Agebat), allowing for program-wide hypotheses to be tested. Agebat variables are divided into three broad (sometimes overlapping) categories: screening measures, predictor/outcome measures, and key moderators and mediators. Domains include: sleep, activity and circadian function, mental health, physical health, cognitive functioning, general functioning, psychosocial and stress, and demographics. Project 1 (Monk) seeks to determine whether the lives of recently widowed seniors (65y+) can be improved by Social Rhythm Therapy in which lifestyle regularity is increased and healthy sleep practices followed. Project 2 (Hall) is concerned with spousal caregivers (65y+) of early Alzheimer patients and an intervention designed to enhance their sleep and reduce the stress of caregiving. Project 3 (Buysse) aims to compare the efficacy of a brief behavioral treatment for insomnia to an information-only control condition in patients (65y+) with the usual morbidities of aging seen in primary care settings. Project 4 (Reynolds) will test the efficacy of restricting time in bed (by 30 minutes) plus education in healthy sleep practices as a means of maintaining or improving sleep quality in the very old (75y+) and thus enhancing their daytime alertness, mood, cognitive function, and well being. Project 5 (Nofzinger) seeks to identify sleep-related functional neuroanatomic changes that accompany age-related changes and intervention related changes of sleep in healthy elders (75y+). Comparisons will be made withinsubjects over a 24 month span, between intervention and control seniors from Project 4, and between seniors and younger adults studied separately. All of the intervention projects will be concerned not only with the effects of the intervention on sleep per se, but also with subsequent mental health, physical health, well-being and functioning using a mediational model. Program-wide research initiatives will be concerned with the specific roles of stress (Halo, lifestyle regularity (Monk), insomnia related to physical ill-health (Buysse), and time spent in bed (Reynolds) on a mixed population of seniors. Again results will be interpreted within a conceptual model linking sleep to health, functioning and well-being. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: AMYGDALA AND SLEEP Principal Investigator & Institution: Benca, Ruth M.; Professor; Psychiatry; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2001; Project Start 10-MAY-2000; Project End 30-APR-2004 Summary: (Adapted from the Investigator's Abstract) Stress-related sleep disorders, notably insomnia, are widely prevalent in the general population. There are few good animal models in which to study the mechanisms underlying insomnia or the sleep abnormalities associated with psychiatric disorders. Dr. Ned Kalin has been studying the role of the amygdala in emotional processing in the rhesus monkey, a relevant model for human emotion and psychopathology. In collaboration with Dr. Kalin, the Principal Investigator has obtained preliminary data from rhesus monkeys with amygdala lesions which suggest that the amygdala mediates stress effects on sleep and
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may be important in organizing REM/NREM sleep cycles as well. In this revised proposal, the Principal Investigator plans to study rhesus monkeys with total, bilateral lesions of the amygdala, and bilateral lesions of the central nucleus of the amygdala, the major output site from the amygdala. Using telemetry, she will compare sleep patterns under normal, unrestrained conditions and in response to a variety of stressors. These studies will establish the role of the amygdala in normal sleep organization as well as in response to emotional and physical stressors. Results obtained from these studies should increase our understanding of the mechanisms underlying sleep abnormalities in psychiatric disorders and insomnia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANTAGONIST OF A2B ADENOSINE RECEPTORS FOR ASTHMA Principal Investigator & Institution: Figler, Robert A.; Adenosine Therapeutics, Llc 300 Preston Ave, 5Th Fl Charlottesville, Va 22902 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 30-SEP-2002 Summary: (Adapted from the Investigator's Abstract): Adenosine administered as an aerosol to asthmatics causes bronchoconstriction, while in non-asthmatics adenosine causes bronchodilation. This occurs because the activation of A2B adenosine receptors on sensitized mast cells triggers degranulation, releasing histamine, leukotrienes, and other allergic mediators. A2B adenosine receptors are blocked by theophylline, a xanthine that is effective in treating asthma. However, theophylline is a non-selective antagonist of all four adenosine receptor subtypes and produces side effects due primarily to A1 receptor blockade, including insomnia and diuresis. The incidence of asthma is increasing and current treatment options are limited. New drugs that are potent and selective antagonists of A2B adenosine receptors have great potential for the treatment of asthma and other allergic diseases. Adenosine Therapeutics, LLC owns the first potent and selective A2B antagonists. The purpose of this phase I proposal is to attempt to identify related structures that have improved aqueous solubility. A candidate compound will be evaluated in pharmacokinetic studies in dogs. Adenosine Therapeutics will also prepare mast cells from canine and human lung and determine if candidate compounds can prevent their degranulation. These studies are preliminary to a phase II SBIR study in which candidate compounds will be evaluated in dog models of asthma. PROPOSED COMMERCIAL APPLICATION: Potent and selective antagoists of A2B adenosine receptors have great commercial potential for the treatment of asthma and other allergic or autoimmune diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: AUTONOMIC DYSREGULATION IN PRIMARY INSOMNIA Principal Investigator & Institution: Richardson, Gary S.; Senior Research Scientist; Behavioral Services; Case Western Reserve Univ-Henry Ford Hsc Research Administraion Cfp-046 Detroit, Mi 48202 Timing: Fiscal Year 2001; Project Start 01-AUG-2001; Project End 31-JUL-2006 Summary: (provided by applicant) Chronic insomnia is a disorder afflicting as many as 10 percent of adults in the US, a substantial proportion of whom have no identifiable underlying cause for the sleep complaint, i.e. primary insomnia (PI). Several lines of evidence implicate central sympathetic nervous system (SNS) dysregulation in the pathogenesis of PI. First, patients with this disorder show evidence of SNS arousal, including increased basal metabolic rates, elevated circulating catecholamines, and increased daytime alertness relative to the degree of nocturnal sleep disruption. Along
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with the SNS, the hypothalamic pituitary adrenal (HPA) axis is also hyperactive in insomnia, implicating a central mechanism common to both axes. Second, epidemiological studies establish a strong link between patients with PI and patients with major depressive disorder (MDD), also characterized by central activation of the SNS and HPA axes. Third, corticotropic releasing factor (CRF), a link between the SNS and HPA axes implicated in the pathogenesis of MDD, causes sleep disruption and hyper-arousal when centrally administered in animal models. In this proposal, we present a model of primary insomnia in which the pathogenic mechanism of this disorder is hypothesized to be dysregulation of central CRF neurons, specifically the delayed restoration of normal CRF levels following stress. This model provides a conceptual foundation for 1) the temporal (intermittent) pattern of manifest sleep disruption in patients with underlying tendency to P1; 2) the link between insomnia and stress; 3) the epidemiological link between MDD and P1; and 4) the hyper-arousal in PI with activation of SNS and HPA axes. It also provides a focus for future therapeutic efforts for this important disorder, suggesting that antagonists of CRF may be useful in reversing insomnia, and in blocking the processes that eventuate in MDD. We propose three experiments to test the CRF model and some of its predictions. In the first experiment, we will examine the status of the SNS and HPA axes in patients with P1, and the clinical correlates of SNS-HPA activation in this population. Second, we will assess the role of the CRF-SNS response in perpetuating insomnia by comparing the effects of sleep disruption (audio tones) in patients with P1 and normal controls, using sleep continuity, urinary catecholamines, daytime function, and subsequent sleep as dependent measures. Finally, we will use a new measure of central CRF function, the DEX-sleep latency test, to test the hypothesis that central CRF tone is higher in patients with P1. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BASIC MECHANISMS OF DELAYED SLEEP PHASE SYNDROMEN 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
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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 •
Project Title: BEHAVIORAL AND PHARMACOLOGICAL TREATMENT FOR INSOMNIA Principal Investigator & Institution: Morin, Charles M.; Professor and President; Laval University Pav. Sciences De L'education Quibec, Pq G1k 7P4 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 30-JUN-2006 Summary: (Adapted from the Applicant's Abstract): Insomnia is a prevalent health complaint which is often associated with functional impairments, reduced quality of life, and increased health-care costs. The specific aims of the proposed study are to (a) evaluate the short- and long-term effects of cognitive -behavior therapy (CBT), alone and in combination with medication, for chronic insomnia, (b) compare the efficacy of different maintenance strategies for combining drug and nondrug therapies to optimize long-term outcomes, and (c) examine the clinical impact of treatment on daytime functioning and psychological well-being. One hundred and fifty (150) adults meeting criteria for chronic insomnia will be randomly assigned to CBT or CBT plus medication. After the acute treatment phase, which will last eight weeks, patients will be entered into an extended treatment lasting six months. Of those treated with CBT alone initially, responders will be entered into an extended CBT or no treatment. Of those receiving the combined CBT plus medication (used on an as needed schedule) or CBT alone (plus medication tapering). Outcome will be evaluated across measures of sleep, clinical ratings, and several indices of daytime functioning. The measures will be administered at baseline, at the end of the acute and extended treatment phases, and at 6-, 12-, and 24month follow-ups. The main research questions are: (a) Is CBT in conjunction with medication more effective than CBT alone for the acute treatment of insomnia? (b) When combining CBT and drug therapy, is it best to discontinue medication after the initial acute treatment or to continue using it on an intermittent (as needed) schedule in order to foster long-term maintenance of sleep improvements? and (c) What is the clinical impact of sleep improvement on daytime fatigue and performance, psychological symptoms, and quality of life? The public health significance of the proposed study is that it will provide useful information about optimal models for integrating behavioral and pharmacological therapies for the clinical management of insomnia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: INSOMNIA
BEHAVIORAL
TREATMENT
FOR
COMORBID
GERIATRIC
Principal Investigator & Institution: Rybarczyk, Bruce D.; Rush-Presbyterian-St Lukes Medical Ctr Chicago, Il 60612 Timing: Fiscal Year 2001; Project Start 15-AUG-2000; Project End 31-JUL-2004
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Summary: Description (adapted from the investigator's abstract): This is a revised application to test the efficacy of an empirically based cognitive-behavioral intervention for older adults with insomnia and co-morbid chronic illness recruited from an HMO population. The primary objective of the study will be to compare the efficacy of behavioral treatments for insomnia among patients with 3 common age-related chronic illnesses: osteo-arthritis (OA), chronic obstructive pulmonary disease (COPD) and coronary artery disease (CAD) because exceptionally high rates of co-morbid insomnia have been found in the 3 groups. A second major objective is to determine whether an effective behavioral treatment can diminish the well-established effects of insomnia on quality of life among those with chronic illness. The proposed study will include random assignment of 3 groups of 55 HMO patients 55 years or older with OA, COPD and CAD and co-morbid insomnia to an 8-week cognitive-behavioral treatment class or placebo control class. The behavioral intervention will be empirically based with both cognitive-behavioral and relaxation approaches. The placebo control group will be a wellness/stress management class. Outcomes will be assessed at 4, 8, and 12 months post treatment follow-up intervals. Sleep quantity and quality will be evaluated using polysomnography, actigraphy and self report measures. Quality of life, functional status and mood will also be assessed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BETA EEG ACTIVITY IN INSOMNIA Principal Investigator & Institution: Perlis, Michael L.; Psychiatry; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2001; Project Start 06-DEC-2000; Project End 30-NOV-2003 Summary: (Adapted from applicant's abstract) It has been estimated that between 10 and 15 percent of the population has chronic Primary Insomnia. Thus, in the United States alone between 27 and 41 million people suffer from a disorder that diminishes their quality of life, negatively impacts on their work performance and puts them at increased risk for medical and psychiatric illness. The economic costs associated with insomnia are estimated to be in the tens of billions of dollars per annum. Despite its prevalence and consequences, little is known about the pathophysiology of insomnia and how it is related to the presenting symptoms of the disorder. Recent work on the spectral components of the sleep EEG show that Beta frequency EEG activity at/around sleep onset and during NREM sleep is increased in patients with Primary Insomnia, in comparison to both good sleeper controls and MDD patients with secondary insomnia. While this suggests that patients with Primary Insomnia exhibit higher than normal levels of CNS arousal at sleep onset and during NREM sleep, little is known, about whether high frequency EEG activity in insomnia is 1) limited to the Beta activity, 2) actually CNS in origin 3), if CNS in origin, preponderant at specific EEG sites, 4) varies with symptom intensity and 5) correlated with the subjective perception of sleep quality and quantity. We propose to undertake one experiment in which three groups of subjects will be studied polysomnographically for four consecutive nights. The subject groups will be 30 patients with Primary Insomnia, 30 patients with insomnia secondary to Major Depression, and 30 good sleeper controls. Digital EEG data from each night of study will be obtained from 10 sites (F3,F4,C3,C4,T5,T6,P3,P4,O1 ,02) and power spectral data will be compiled for each of the first 4 NREM and REM cycles and for each stage of sleep. Group differences for Beta-I (14-20Hz), Beta-2 (20-35Hz), Gamma (35-45Hz) and Omega (45-125 Hz) will be assessed taking into account site-to-site and night-to-night variability. In addition, we will evaluate the extent to which high frequency activity is associated with the perception of sleep quality and quantity.
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Insomnia
Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BRIEF BEHAVIORAL TREATMENT OF INSOMNIA IN PRIMARY CARE Principal Investigator & Institution: Buysse, Daniel J.; Associate Professor; 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: Insomnia is a widely prevalent and typically chronic health problem among the elderly that is associated with significant psychological, physical, and economic consequences. Previous studies have demonstrated the efficacy and durability of behavioral treatments for primary insomnia, but there is less evidence regarding their utility in routine practice settings, in patients with comorbid medical and psychiatric disorders, and in a brief treatment format. The general aim of this study is to compare the efficacy of a brief behavioral treatment for insomnia (BBTI) to an information-only control condition in patients with the usual morbidities of agina seen in primary care settings. Specific aims for this study are 1. To test the short-term efficacy of BBTI versus an information-only control for improving sleep and health outcomes among individuals with insomnia in primary care settings; 2. To test the durability of BBTI among individuals with insomnia in primary care settings; and 3. To compare older adults with and without insomnia in terms of mental health, physical health, sleep and circadian function, and general functioning. We will also address the following Program-wide aim: To evaluate the effects of physical and mental health on sleep and the response to sleep interventions, and to evaluate the effects of sleep interventions on health and functioning. The study will include 50 subjects in each randomly-assigned treatment cell. Baseline measures will include each of the domains in the Program Project battery (Agebat). BBTI focuses on sleep education, healthy sleep practices, and behavioral interventions to improve insomnia. It is delivered in two sessions over a four-week interval by a nurse therapist, supplemented by brief weekly telephone calls. Treatment integrity will be monitored by audiotape ratings, and treatment adherence by sleep diaries. The information-only control condition is designed to approximate the type of information that may be available in a physician's office, and will consist of providing patients with three patient brochures that address sleep in aging, insomnia, and sleep hygiene. Short-term outcome will be assessed by administration of Agebatat the end of one month, and durability of BBTI will be evaluated by readministration of the clinical portions of Agebatat six months, and both clinical and polysomnographic components of Agebat at twelve months. This study represents a hybrid between a classic efficacy study, characterized by recruited and highly selected samples with "pure" forms of a disorder, and an effectiveness study, with a large sample of subjects treated in their usual care setting. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BRIGHT LIGHT TREATMENT OF SLEEP DISTURBANCE IN ELDERLY Principal Investigator & Institution: Campbell, Scott S.; Professor; Psychiatry; Weill Medical College of Cornell Univ New York, Ny 10021 Timing: Fiscal Year 2001; Project Start 01-FEB-1989; Project End 31-DEC-2002 Summary: (Adapted from applicant's abstract): It is widely recognized that changes in the sleep/wake system accompany the aging process. As a consequence, a large proportion of older people complain of significant sleep disturbance-Age-related sleep
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changes are commonly expressed as shallow and fragmented sleep, and multiple, often prolonged awakenings, particularly in the second half of the night. Few older subjects report difficulties getting to sleep. Therefore, sleep disturbance in people over 65 is generally considered to be a disorder of maintaining, rather than initiating, sleep. Recent evidence indicates that timed exposure to bright light can be effective in managing these age-related sleep changes by acting directly on the circadian timing system. Yet, effectiveness, of light treatment may be compromised by compliance problems associated with the time required for, and the constraints involved in, the treatment regimen. Response to treatment is likely to be affected also by one's recent history of light exposure. Until issues of compliance are fully understood and effectively dealt with, light treatment for age-related sleep disturbance cannot be employed to its full potential. This COMPETING CONTINUATION will examine three important issues related to compliance: First, it is proposed to quantify the effects of prior light history on the phase-shifting capacity of bright light. Second, a novel procedure for light delivery will be tested, the development of which may hold promise for significantly enhancing user compliance. Finally, an in-home treatment will be implemented which administers light in a manner that may be more acceptable to patients. In the lab-based studies, circadian variables of young (65 yrs) will be monitored at baseline, and throughout an interval during which subjects' prior light history is controlled, immediately preceding exposure to 1) a conventionally-administered bright light phase-shifting stimulus, or 2) a bright light phase-shifting stimulus administered using a non-ocular site for phototransduction. In the treatment study, two groups of healthy, older subjects (>65 yrs) who complain of sleep maintenance insomnia, and whose complaints are verified polygraphically, will undergo either 1) a one-month regimen of timed room-light exposure combined with timed light avoidance, or 2) a well-validated control condition, while living at home and continuing normal daily activities. All three studies address issues crucial to the successful development and implementation of bright light treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CBT FOR CHRONIC INSOMNIA IN BREAST CANCER SURVIVORS Principal Investigator & Institution: Riggs, Raine L.; Psychiatry; Dartmouth College 11 Rope Ferry Rd. #6210 Hanover, Nh 03755 Timing: Fiscal Year 2003; Project Start 26-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): The primary goal of the proposed study is to determine the efficacy and patient acceptability of a manualized cognitive behavioral treatment for chronic insomnia (CBTCI) in early stage breast cancer survivors with chronic insomnia. Sleep complaints are common among cancer survivors. In particular, chronic insomnia is almost twice as prevalent among breast cancer survivors as it is among the general population. Chronic insomnia may result in fatigue, cognitive impairments, mood disturbance, increased pain, and immunosuppression, all of which negatively affect a woman's quality of life and may play a role in the recurrence of cancer. While a highly efficacious, safe intervention exists for the treatment of chronic insomnia, it has not yet been applied to cancer survivors. In the proposed study, 60 early stage breast cancer survivors, matched on potentially important prognostic factors such as age, menopausal status, and time elapsed since initial treatment, will be recruited from the Breast Oncology Center at the Dana Farber Cancer Institute. The women will be randomized to one of two groups. One group of breast cancer survivors will receive eight, individual, weekly CBTCI sessions and the other group will receive eight, individual, weekly cognitive behavioral placebo sessions (CBP). All participants
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Insomnia
will provide self-report data on their sleep, fatigue, depressive symptoms, and pain levels throughout the study. Participants will also complete patient satisfaction questionnaires at the conclusion of treatment to assess treatment acceptability and credibility. It is hypothesized that the women in the CBTCI group will experience statistically and clinically significantly improvements in self-reported sleep and sleep quality, while the women in the CBP group will remain stable. It is also hypothesized that increased sleep quality will be related to decreased levels of depressive symptoms, fatigue, and pain. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CBT DEPENDENCE
FOR
INSOMNIA
IN
PATIENTS
WITH
ALCOHOL
Principal Investigator & Institution: Arnedt, J Todd.; Psychiatry and Human Behavior; Brown University Providence, Ri 02912 Timing: Fiscal Year 2003; Project Start 29-SEP-2003; Project End 31-AUG-2006 Summary: (provided by applicant): As many as two-thirds of patients complain of insomnia during the early stages of recovery from alcohol dependence, and sleep remains grossly disturbed even with sustained abstinence. Recent evidence suggests that sleep disturbance is an important indicator of future drinking status in this population, however no study has assessed the efficacy of a cognitive-behavioral insomnia treatment for reducing the severity of subsequent drinking. The proposed project is designed to develop an 8-week cognitive-behavioral treatment for insomnia that is specific to individuals with alcohol dependence in early recovery. We will also establish the preliminary efficacy of the treatment in a randomized, controlled pilot study, and gather preliminary evidence as to whether the treatment reduces the quantity and frequency of drinking at 3- and 6-month follow-up. During the first phase of the project, we will develop the following in consultation with recognized experts in alcohol and insomnia research: (1) a manual for the cognitive-behavioral treatment for insomnia - alcohol [CBTI-A]; (2) a training program for therapists; and (3) measures to assess therapist competence and treatment fidelity. The CBTI-A will then undergo an open trial with 5 to 10 recently abstinent patients with alcohol dependence to assess barriers to treatment and acceptability of the approach with this population. Following further refinements to the treatment manual and fidelity measures, two therapists will be trained, and then we will conduct a randomized, controlled pilot study to compare the efficacy of CBTI-A to a behavioral placebo treatment [BPT] for improving selfreported sleep continuity in 60 recently abstinent alcoholic participants. Data analyses will focus on the effect size of the treatment on self-reported sleep measures and participant retention. At 3 and 6 months post-treatment, we will assess sleep continuity and drinking status to determine the maintenance of sleep treatment gains, and to gather preliminary data on the effect size of the intervention for reducing quantity and frequency of drinking. The data from the randomized controlled pilot trial will be used to support a large-scale clinical trial to assess specifically the prophylactic efficacy of CBTI-A for preventing, delaying, or reducing the severity of future relapse. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CELL-PERMEANT CLOCK PROTEINS Principal Investigator & Institution: Johnson, Carl H.; Associate Professor; Biological Sciences; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 10-SEP-2002; Project End 30-JUN-2004
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Summary: (provided by applicant): Humans and most other organisms manifest circadian (daily) rhythms that are controlled by an endogenous biochemical oscillator. Many cellular processes, including cell division, enzyme activity, and gene expression, are timed by this oscillator. These "biological clocks" are important to human physiology. For example, psychiatric and medical studies have shown that circadian rhythmicity is involved in some forms of depressive illness, "jet lag," drug tolerance/efficacy, memory, and insomnia. Therefore, understanding the biochemical mechanism of circadian clocks may lead to procedures which will be useful in the diagnosis and treatment of disorders that are relevant to sleep, mental health, and pharmacology. The salient properties of circadian clocks-24 hour time constant, high precision, temperature compensation-are presently impossible to explain biochemically. Although recent breakthroughs in the field of circadian rhythms have identified a number of proteins that appear to act as clock components, we have only just begun to understand how these components interact functionally with themselves and the environment. In model systems, it has been possible to reset the phase of circadian rhythms by induction of clock protein synthesis at specific phases. This approach has been difficult to accomplish in mammalian systems. The current project will test hypotheses concerning the significance of rhythmic clock protein abundance in mammals by using new methods to introduce proteins directly into cells by peptidemediated transduction across cell membranes. This technology will allow us to modulate the intracellular concentration of clock proteins in cells, tissue slices, and intact animals. These studies will yield results of theoretical importance, but also have the potential for designing treatments for jet lag, insomnia, and other clock-related disorders. This project is appropriate for the NIMH Exploratory/Developmental Grant (R21) Program because it fulfills all of the following primary criteria: (1) innovative research directions, (2) exploration of approaches that are new to a substantive area, and (3) development of new technologies and methods. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CELLULAR TOLERANCE MECHANISM OF ABERRANT PROTEINS Principal Investigator & Institution: Ng, Davis T.; Assistant Professor; Biochem and Molecular Biology; Pennsylvania State University-Univ Park 201 Old Main University Park, Pa 16802 Timing: Fiscal Year 2001; Project Start 01-MAY-1999; Project End 30-APR-2004 Summary: The biogenesis of secreted and resident proteins of the secretory pathway is an essential cellular function of all organisms. As a highly regulated process, the cell has evolved mechanisms to assure only properly folded and assembled proteins reach their ultimate destinations. This 'quality control mechanism' retains aberrant proteins at the site of synthesis, the endoplasmic reticulum (ER), and targets them for degradation. The importance of faithfully regulating protein biosynthesis is underscored by the numerous human diseases including Alzheimer's, Cystic Fibrosis, Huntington's, Creutzfeldt-Jakob, and familial insomnia caused by aberrant protein conformation. The long-term objectives of this research are to understand the regulation and mechanisms governing secretory protein biogenesis. This project focuses on a novel cellular mechanism required to tolerate aberrant proteins until they can be degraded. This is an active mechanism requiring activation of an intracellular signal transduction pathway known as the unfolded protein response. Surprisingly, the tolerance mechanism is functional in the absence of ER protein degradation making both facets of ER quality control particularly amenable for investigation. The primary goals of the project include 1) using genetic and biochemical approaches to identify genes required for tolerance, 2)
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Insomnia
purifying and characterizing aberrant protein complexes from tolerant and intolerant cells, 3) ultrastructural analysis of cells expressing aberrant proteins to precisely localize these complexes and study their morphological consequences in tolerant and intolerant cells, 4) defining physiological conditions requiring a tolerance function, and 5) isolating novel ER protein degradation mutants and their genes with an emphasis on common factors to establish a genetic linkage to tolerance. The simple eukaryote Saccharomyces cerevisiae used for the studies is particularly well-suited. It provides a combination of powerful genetic and biochemical approaches necessary to gain a comprehensive understanding of the mechanisms underlying the detoxification and degradation of aberrant proteins. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CHARACTERIZING THE NIGHT EATING SYNDROMEN Principal Investigator & Institution: Stunkard, Albert J.; Professor Emeritus of Psychiatry; Psychiatry; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 01-SEP-2000; Project End 31-AUG-2003 Summary: Description (adapted from the investigator's abstract): The present application is designed to delineate the behavioral and biological characteristics of a newly proposed eating disorder-the night eating syndrome-and to explore the neuroendocrine mechanisms underlying its clinical characteristics. It was recently shown that persons selected on the basis of reports of morning anorexia, evening hyperphagia and insomnia manifest a distinct clinical entity, characterized by greatly increased food intake late in the day and evening, a lowered mood that falls during the afternoon and evening and frequent nighttime awakenings during which small, high carbohydrate snacks are consumed. Study of a different group of night eaters showed elevated cortisol levels throughout the 24 hours and attenuation in the nighttime rise in melatonin and leptin. This application is designed to more clearly delineate the syndrome by replicating and extending a previous study, this time using the same subjects for the behavioral and neuroendocrine measurements. The study will involve two phases. Phase I will consist of a 1-week outpatient study to determine the distinctive behavioral features of the night eating syndrome by comparing 30 night eaters with 30 persons suffering from binge eating and 30 persons without an eating disorder. During the week subjects will keep careful records of all food and fluid intake, and will wear sensitive motion sensors which record all nighttime awakenings. Phase II will consist of a 3-day hospitalization in the Clinical Research Center of the Hospital of the University of Pennsylvania comparing 15 night eaters with 15 non-eating-disordered controls. Polysomnography will determine the sleep architecture of the three groups, particularly the sleep stage during which arousals occur in the night eaters. Levels of melatonin, leptin and cortisol will be determined every 30 minutes, allowing far greater precision in determining circadian rhythms, than was possible with the 2-hour interval in our previous study. Statistical analyses will compare the results of the behavioral, sleep and neuro-endocrine studies with a goal to have the most complete characterization of an eating disorder yet undertaken. Exploratory analyses will include correlation among the behavioral variables (food intake, mood, and nighttime awakenings) and the neuroendocrine variables to explore determinants of the clinical picture. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CHRONIC NEUROCHEMISTRY
BENZODIAZEPINES:
BEHAVIOR
25
AND
Principal Investigator & Institution: Greenblatt, David J.; Professor and Chair; Pharmacol & Exper Therapeutics; Tufts University Boston Boston, Ma 02111 Timing: Fiscal Year 2001; Project Start 30-SEP-1987; Project End 31-JAN-2006 Summary: Benzodiazepine agonists continue to be the principal pharmacologic option available for the treatment of anxiety, panic disorders, and insomnia. Despite an overall record of efficacy and safety that is generally favorable, concerns regarding tolerance, dependence, withdrawal syndromes, and abuse of benzodiazepines remain issues of medical and public health importance. Also of concern is the usage of these agents by the elderly, who may have increased susceptibility to adverse CNS depressant effects. There is continuing need for basic mechanistic data on the causes and consequences of tolerance and withdrawal; such data can form the basis for strategies to identify patients at highest risk, or to develop other pharmacologic interventions to minimize the risk of tolerance and dependence. We propose to continue and broaden our ongoing research program having this overall objective. The core of the model involves male CD-1 mice that receive continuous infusions of benzodiazepine agonists, or vehicle control, for up to 14 days via implanted osmotic pumps. During the period of infusion, and in the 7-day post-infusion withdrawal period, the following outcomes are determined: computerized ambulatory activity; pentylenetetrazole seizure threshold; in vivo benzodiazepine receptor occupancy; in vitro receptor binding; GABA(A) receptor function; receptor autoradiography; receptor subunit mRNA expression; and plasma and brain concentrations of infused substances. The principal research questions to be addressed include the following: a. Do benzodiazepine agonists with relative selectivity for the BZ1 receptor subtype have reduced liability to produce tolerance, dependence and withdrawal? b. Does the protein kinase C second messenger pathway have a modulatory role in benzodiazepine-associated tolerance? c. Does the excitatory amino acid (EAA) receptor system co-modulate the development of tolerance and withdrawal associated with benzodiazepine agonists, and does pharmacologic antagonism of specific EAA receptor systems modify these phenomena? d. Do aging organisms have differential patterns of benzodiazepine tolerance and withdrawal? Are such differences explained by protein kinase C or EAA regulatory systems? These studies should continue to provide mechanistic data relevant to the clinical management and prevention of tolerance and dependence problems associated with therapeutic use of benzodiazepine agonists. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CIRCADIAN OSCILLATORS IN CULTURED MAMMALIAN TISSUE Principal Investigator & Institution: Menaker, Michael; Commonwealth Professor; Biology; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2002; Project Start 01-JAN-1997; Project End 31-JAN-2007 Summary: (provided by applicant): Our overall aim is to elucidate the structure of the mammalian circadian hierarchy. To accomplish this we need to know which organs and tissues contain independent circadian oscillators and how each is coupled to the others and to the environment to control phase and produce adaptive temporal organization. Our guiding hypothesis is that circadian oscillators in the suprachiasmatic nucleus of the hypothalamus (SCN) normally synchronize circadian oscillators in the brain and periphery using a variety of different signals. These include neural impulses, hormonal signals and, unexpectedly, behavioral signals generated by the SCN, modified by the
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Insomnia
environment, and acting on peripheral oscillators directly through the consequences of the behavior (e.g., feeding cycles entrain the circadian oscillators in the liver). Using transgenic rats in which the mouse Per1 promoter has been linked to a luciferase reporter, we have been able to measure circadian rhythms of light emission from a variety of cultured tissues including the SCN and peripheral tissues such as lung, liver and cornea. We will assess the degree to which the oscillators in peripheral tissues manifest canonical circadian properties such as temperature compensation. We will test the hypothesis that peripheral oscillators are maintained and regulated by a variety of different signals originating in the SCN by lesioning that structure and subsequently culturing peripheral tissues that oscillate when derived from intact animals. We will test the efficacy of several signals that putatively entrain peripheral oscillators (e.g., norepinephrine for pineal, insulin for liver, forced exercise for lung, melatonin and body temperature as systemic signals). Detailed knowledge of the coupling signals involved will eventually enable us to modify the phase of particular oscillators within the system for therapeutic purposes. This information is essential for the rational use of circadian approaches to the management of the performance deficits produced by shift work, insomnia and pathologies with circadian components such as seasonal affective disorder (SAD). Furthermore, it is basic to the design of treatments for many serious conditions (e.g., high blood pressure, cancer) in which responses to therapeutic agents are modulated both positively and negatively by the circadian system. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CIRCADIAN REGULATORY CIRCUITS IN DROSOPHILA Principal Investigator & Institution: Hardin, Paul E.; Professor; Biology and Biochemistry; University of Houston 4800 Calhoun Rd Houston, Tx 77004 Timing: Fiscal Year 2001; Project Start 01-JUN-2000; Project End 31-MAY-2004 Summary: (Applicant's abstract reproduced verbatim): One of the most intriguing questions in biology is how organisms keep circadian time in the absence of daily environmental cues. Essentially all organisms (microbes, plants, and animals) use an endogenous timekeeping mechanism, or clock, to activate various physiological and behavioral rhythms at the appropriate time of day. Our understanding of the clock is particularly important for human health and well being since basic physiological activities including sleep, endocrine and cardiovascular function and drug tolerance are rhythmically controlled. Clock dysfunction is related to several common mental disorders such as manic-depressive illness, seasonal affective disorder and insomnia. Extensive research has shown that the timekeeping mechanism of the clock, called a circadian oscillator, is comprised of an autoregulatory feedback loop in gene expression. One of the most extensively characterized feedback loop oscillators is that from the fruit fly Drosophila melanogaster. Since the Drosophila feedback loop oscillator uses essentially the same set of genes as the mammalian circadian feedback loop oscillator, what we learn about the mechanism underlying the Drosophila feedback loop function may be directly applicable to function of the mammalian feedback loop. We recently showed that the Drosophila circadian oscillator is comprised of two interlocked negative loops: the well studied per/tim feedback loop in which per and tim transcription is activated by dCLK-CYC and repressed by PER-TIM, and a novel dClk feedback loop in which dClk transcription is repressed (directly or indirectly) by dCLK-CYC and derepressed via PER-TIM interactions with dCLK-CYC. From this data, we make several predictions about the molecular interactions needed to regulate rhythmic dClk expression. These predictions form the basis for the specific aims of this application.: 1) identifying the factor(s) responsible for dClk activation, 2) determining how dCLK and
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CYC repress dClk transcription and 3) determining whether PER-TIM interactions with dCLK-CYC are capable of de-repressing dClk transcription. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CLINICAL EVALUATION OF BOTANICAL DIETARY SUPPLEMENT Principal Investigator & Institution: Derman, Richard J.; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2003 Summary: The overall objectives of this project are to conduct Phase I and II clinical trials of black cohosh (Cimicifuga racemosa) and red clover (Trifolium pratense), to be used for women's health problems-for menopausal hot flashes (primarily) and other somatic symptoms. Observational and epidemiological studies demonstrated that black cohosh is effective for menopausal women, and safe (at least in short-term). Phase I: The aims of this study is to determine safe doses (acute toxicity) of extracts of both botanicals, to be used in the subsequent Phase II clinical trial. Three doses will be tested over a one-week period in an attempt to determine symptoms of acute toxicity. There will be 5 subjects for each of 3 dosages (1X, 2X, 3X) of the 2 botanicals. (N=30) The goal is a sample size large enough to estimate unknown parameters Also studied will be pharmacokinetics (hourly bloods) absorption, distribution, metabolism, elimination, and pharmacological mode of action and side effects in healthy menopausal women. Phase II: This is a one year, randomized, controlled, double-blind efficacy study, the primary aim of which is to evaluate the efficacy of black cohosh and red clover, over a "safe dose range," for menopausal hot flashes. Additional goals are to assess these botanicals for other menopausal symptoms such as insomnia, joint pain, vaginal dryness, and dyspareunia (using Kupperman Index, bleeding scales and index of sexual function). They will also assess longer-term risks and safety issues and to determine changes in biomarkers (such as bone turnover and lipids) associated with use of these botanicals. Most previous studies of black cohosh lasted at most 6 months. Longer-term (1-year) safety data will be evaluated. In particular, incidence of endometrial hyperplasia, breakthrough bleeding, and other side effects will be determined. Subjects (n=112) will be randomized into one of 4 treatment groups (28/gr): placebo, Prempro 0.625/2.5, black cohosh and red clover. Also they will take blood samples to measure DNA oxidation products for measurements of DNA strand breaks using the comet assay to determine if DNA in peripheral blood leukocytes is being protected from damage through the antioxidant properties of the 'active' compounds or whether DNA damage is being produced (indicator of toxicity). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CLONIDINE SYNDROMEN
TREATMENT
FOR
NEONATAL
ABSTINENCE
Principal Investigator & Institution: Gauda, Estelle B.; Associate Professor; Pediatrics; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-JUL-2006 Summary: (provided by applicant): In the United States, as many as 20,000 babies a year are born to opioid ("narcotic") addicted mothers. Like their mothers, these infants are opioid dependent. Following birth, the infant is removed from its opioid source, inducing a withdrawal syndrome in these infants. Withdrawal symptoms in newborns include vomiting, diarrhea, poor feeding, tachycardia, hypertension, diaphoresis, restlessness, insomnia, irritability, tremors, clonus, hyperphagia with poor growth and
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acidosis, reversible neurologic abnormalities, and even seizures. This complex of signs and symptoms is referred to as neonatal abstinence syndrome (NAS). Reinstitution of opioids followed by a slow tapering protocol is currently the standard of care, necessitating prolonged hospitalization from weeks to months. Clonidine is a nonnarcotic central alpha2-adrenergic receptor agonist that blocks the effects of overexcitation of the sympathetic nervous system and is an approved treatment for opioid withdrawal in adults. We currently have a physician sponsored IND (#63,781) to study the effect of clonidine as adjunct therapy to opioids for the treatment of NAS. This proposal will test the hypothesis that combination therapy of clonidine and opioids is 1) safe and efficacious, 2) allows reduced amount of opioid drug use, and 3) results in shorter time of treatment and hospitalization. This will be accomplished in a randomized, placebo controlled double blind clinical trial comparing diluted tincture of opium (DTO) combined with a placebo (control) vs. DTO combined with clonidine. Additional sub-studies include determination of 1) pharmacokinetics and pharmacodynamics of DTO and clonidine in the enrolled cohort and 2) further safety evaluation by evaluating developmental outcome on the Bayley Scale of Infant Development (BSID) at 6 and 12 months of age. Pharmacokinetics will be determined by measuring serum concentrations of clonidine and morphine and analyzing volume of distribution, elimination half-life and clearance. These results will have important clinical implications and may change the standards of care not only for management of infants with severe NAS, but also for the management of infants and children, after long-term iatrogenic opioid exposure for instance following prolonged analgesia for mechanical ventilation or multiple operations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: COMBINED BEHAVIORAL/PHARMACOLOGICAL THERAPY FOR INSOMNIA Principal Investigator & Institution: Wohlgemuth, William K.; Psychiatry; Duke University Durham, Nc 27706 Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 31-AUG-2006 Summary: (provided by Applicant): Chronic insomnia is a common and significant health problem. Fortunately, the poor sleep of insomniacs is improved by both pharmacological and behavioral treatments as recent literature reviews have clearly documented. Each of these treatments, though, has accompanying strengths and weaknesses. Pharmacotherapy works rapidly, but tolerance, dependence and loss of efficacy occur with extended use. Behavioral therapy is not fast-acting and requires a few weeks of practice before benefits are realized. In addition, during this initial phase of behavioral therapy patients often complain of feeling worse than they did prior to treatment. However the improvements in sleep due to behavioral treatment are quite durable. A combination treatment which takes advantage of the strengths of both pharmacological and behavioral therapy is a reasonable approach to treating insomnia. In spite of the compelling rationale for combining the treatments, empirical results have been disappointing. Recent findings have suggested that by adding pharmacotherapy to behavioral therapy long-term treatment gains are diminished. Our preliminary data suggest that extended, intermittent use of hypnotics is not necessary when patients are concurrently treated with behavioral therapy. Our analysis of week-to-week sleep changes among patients treated with behavioral therapy alone demonstrates that significant improvement occurs by the second week of treatment. A sensible approach to combining pharmacotherapy and behavioral treatment would be to discontinue hypnotics when sleep begins to improve due to the behavioral therapy. If hypnotic use
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is restricted to the first three weeks of treatment, we expect that poor sleep will rapidly improve and initial discomfort will be minimized. In addition, because the initial discomfort will be minimized we expect that subjects who receive the combination treatment will be better able to comply with, and remain more engaged in, the cognitive-behavioral treatment regimen. Also, because of the reduced discomfort in the early stages of treatment, more subjects in the combined treatment will stay in treatment. Furthermore, we do not expect this limited use of pharmacotherapy to diminish the long-term treatment gains. Our preliminary data have provided initial support for our expectations and the proposed study is designed to confirm these hypotheses. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INSOMNIA
COMPUTERIZED
SELF-HELP
TREATMENT
FOR
PRIMARY
Principal Investigator & Institution: Riley, William T.; Director of Research; Personal Improvement Computer Systems 12007 Sunrise Valley Dr, Ste 480 Reston, Va 22091 Timing: Fiscal Year 2003; Project Start 01-SEP-2000; Project End 30-JUN-2005 Summary: (provided by applicant): Although nearly 15 percent of adults experience chronic primary insomnia, few have sought or have access to effective behavioral treatments for this condition. The purpose of this project is to design, develop, and evaluate a computerized self-help intervention that provides a comprehensive behavioral treatment of insomnia. A Phase I prototype of the Insomnia Assessment and Treatment Program (IATP) was developed which assessed sleep and wake states using an active sleep sampling procedures and then implemented a stimulus control and sleep restriction intervention. The resulting prototype was evaluated with 86 subjects, comparing the IATP to a comparison group provided with monitoring and educational treatment components only. Despite the active components of the comparison group, the IATP condition produced superior improvement on most of the sleep parameters evaluated during the trial. For Phase II, the program will be redesigned and redeveloped on a specific purpose platform. The program will be evaluated in a randomized controlled trial of 200 subjects with chronic primary insomnia, comparing the IATP treatment program to a self-help behavioral treatment book for insomnia and the IATP device for monitoring purposes only. Subjects will be evaluated at baseline and at weeks 7, 14, and 28 on sleep diary and self-report data of sleep quality, efficiency, and impairment. Home-based, multi-night polysomnography also will be performed on a subset of the sample at baseline and at 14 weeks. The results of this project could produce an empirically validated behavioral treatment for insomnia, which is easily accessed by the millions of people suffering from chronic primary insomnia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CORE--DATA MANAGEMENT AND STATISTICS Principal Investigator & Institution: Mazumdar, Sati; Associate Professor; 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: Core C comprises the data management and statistics core of the AgeWise program. It will handle all aspects of data storage, retrieval and analysis (including statistical analysis) downstream from actual data collection. The premise and fundamental hypotheses to be tested by projects in AgeWise are that protecting sleep in later life will contribute to preventing or slowing declines in functional status and will
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promote the preservation of good physical and mental health for as long as possible in elderly vulnerable to functional decline by the challenges of bereavement, care-giving, insomnia in medical illness, and age itself as they enter the final years of life. Core C will not only be involved in the data management and analysis of data from individual component projects, but also from the AgeWise program as a whole. Program-wide data will be used to explore the mediating role of sleep disruption in determining the health and well-being subsequent to common late-life challenges. The AgeWise program seeks to perform an ambitious program of research involving a large number of data from polysomnography, intervention sessions and the collection of a broad range of health, psychosocial and functioning domains. Our laboratories have had three decades of experience in handling such data. Core C will be composed of two interrelated components: Data Management and Statistics. Under the expert guidance of Dr. Victoria Grochocinski, the data management component will handle all aspects of data processing, storage, and analysis downstream from data collection which will be carried out in Core B (Data Collection - Buysse). Consistency across data collection and management methods will allow investigators prompt access to the data pertaining to their component projects. The statistical component of Core C will be lead by Dr. Sati Mazumdar and Dr. Hernando Ombao, who will work closely with Drs. Buysse, Hall, Monk, Nofzinger and Reynolds in their component projects. An appropriate level of statistical standardization and sophistication in the conduct of statistical analyses will be maintained. Our analytic approach consists in examining the data carefully through descriptive analysis prior to any statistical modeling or inference. A critical look at all data is also necessary for the program-wide research agendas which are part of all five component projects. Data reductions, efficiency in analysis, controlling of type I error and parsimony in analysis are important considerations in our approach. Cutting-edge statistical methodologies will be used in all our analyses. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DEVELOPMENT OF CAREGIVER SLEEP INTERVENTION Principal Investigator & Institution: Carter, Patricia A.; None; University of Texas Austin 101 E. 27Th/Po Box 7726 Austin, Tx 78712 Timing: Fiscal Year 2003; Project Start 14-APR-2003; Project End 31-MAR-2006 Summary: (provided by applicant): In the year 2002 family caregivers are expected to provide hundreds of thousands of hours of care for over 1.2 million people diagnosed with cancer in the United States. As a result of providing this care, family caregivers report difficulty initiating and maintaining sleep (insomnia), moderate to severe depressive symptoms, and poorer quality of life. While depressive symptoms are not unexpected among those caring for a family member diagnosed with a potentially lifethreatening disease, these symptoms can become so severe that caregivers become "patients" themselves and are forced to relinquish the caregiver role, resulting in institutionalization of the person with cancer. Many caregivers report that with a "good night's sleep", coping with the challenges of providing care is improved, depressive symptoms are decreased and quality of life improves. Pharmacological therapies and standard behavioral sleep interventions are problematic for caregivers because of the overwhelming needs of the ill person. The purpose of this study, therefore, is to test a behavioral CAregiver Sleep Intervention (CASI) designed for and delivered in a manner that addresses the specific needs and sleep goals of family caregivers of persons with cancer. The specific aims of this study are to: (1) explore the feasibility of the CAregiver Sleep Intervention (CASI) with family caregivers of persons with cancer; and (2) examine the effects of the CASI on sleep quality (PSQI and Actigraph), depressive
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symptoms (CESD) and quality of life (CQOLC) of caregivers of persons with cancer. Self report and physiological data will be collected from both intervention and control participants six times over a 4 month period (baseline, week 3, week 5, and at 2, 3, and 4 months post baseline). Caregivers receiving the CASI intervention will be asked for their perceptions of the value and usefulness of the intervention and suggestions for modifications in the intervention structure or content. The intervention effect will be computed using Cohen's effect size d. Data obtained from this pilot test of the intervention will be used to support the application for a full-scale trial of the proposed Caregiver Sleep Intervention (CASI). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EPIDEMIOLOGY OF INSOMNIA & MENTAL ILLNESS IN ADOLESCENCE Principal Investigator & Institution: Johnson, Eric O.; Research Scientist; Psychiatry; Case Western Reserve Univ-Henry Ford Hsc Research Administraion Cfp-046 Detroit, Mi 48202 Timing: Fiscal Year 2001; Project Start 01-JUN-2000; Project End 31-MAY-2005 Summary: (Adapted from the Applicant's Abstract): This is a new RO1 application for a five-year study of the epidemiology of insomnia, mental disorders and substance use during adolescence. The application fits within two NIMH priority areas: 1) the principal investigator is a new investigator, and 2) the subject matter places this application under a response to PA95-014, Basic and Clinical Research on Sleep and Wakefulness. The primary purpose of the proposed study is to examine pathways from insomnia to specific mental disorders and substance use during adolescence. More specifically, we will: 1 ) estimate the increased risk of specific mental disorders and substance use attributable to insomnia among adolescents; 2) assess the occurrence of insomnia as prior, concurrent or subsequent to mental/behavioral problems and substance use, as well as chronic and episodic insomnia, by examining the natural course of insomnia; and 3) estimate the prevalence and incidence of insomnia among adolescents in an epidemiologically defined population. We propose a prospective study of a population sample of 1,000 adolescent and parent pairs, with an assessment at baseline and again after a 24-month interval. Adolescents will be 13 - 15 years old at baseline. A random sub-sample of participants (N=156) will be designated for a longitudinal sub-study with monthly assessments of sleep disturbances in order to examine the natural course of insomnia. The proposed prospective study provides a unique opportunity to extend prior research on the nature and potential sequelae of insomnia in adolescence. With this epidemiologic grounding, future examination of HPA axis dysregulation and polysomnographically determined sleep architecture could provide information on potential mechanisms of the hypothesized links between insomnia, mental disorders and substance use. Similarly, with support for the hypothesized prospective increased risk for mental disorders and substance use associated with insomnia, the proposed research may also provide grounding for an intervention trial, treating adolescent insomnia in order to reduce the risk of mental disorders and substance use. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: FATIGUE INTERVENTION
&
BREAST
CANCER-A
BEHAVIORAL
SLEEP
Principal Investigator & Institution: Berger, Ann M.; Adult Health and Illness; University of Nebraska Medical Center Omaha, Ne 681987835
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Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 30-APR-2007 Summary: (provided by applicant) Higher fatigue levels are found in women with stage I or II breast cancer receiving adjuvant chemotherapy (CT) who adopt patterns of daytime inactivity and nighttime restlessness and have more symptom and psychological distress. Interventions that improve sleep quality and reduce daytime fatigue in persons with insomnia may also benefit women receiving adjuvant CT. Using selected factors from Piper's Integrated Fatigue Model (IFM), a randomized, controlled clinical trial will compare women with breast cancer who receive a four component behavioral sleep intervention to women in the attentional control group during and after adjuvant CT. The intervention is designed to reduce fatigue in these women by promoting daytime activity, improving sleep quality and decreasing symptom and psychological distress. The aims of this study are to: 1) Compare the immediate (sleep/wake, activity/exercise, symptoms, psychological distress) and consequent (fatigue) outcomes of a four component behavioral sleep intervention (sleep hygiene counseling, relaxation therapy, sleep restriction, and stimulus control) in an experimental group (n=110) with outcomes in an attentional control group (n=110) in women with stage I or II breast cancer during 4 or 8 cycles of adjuvant CT, at 30, 60, and 90 days after their last treatment, and 1 year after their first baseline; 2) Determine the extent to which factors selected from the IFM influence fatigue intensity levels a) in the total sample and 1 year after the first treatment and 3) Evaluate the adherence to the refined behavioral sleep intervention and preferences for sleep hygiene and relaxation therapy techniques in the experimental group over time. Women will be randomized on the basis of good or poor sleeping history and intent to treat (4 versus 8 cycles of CT) to an experimental or attentional control group. Using the co-scientist model, the experimental group will follow an Individual Sleep Promotion Plan negotiated with the investigator with regularly scheduled reinforcements and revisions. The control group will receive equal time and attention regarding general topics and nutrition. Established instruments include the Piper Fatigue scale, Hospital Anxiety and Depression Scale, SF36 Health Survey, Symptoms Experience Scale, Daily Diary and Insomnia Severity Index. Objective measures include wrist actigraphs, hemoglobin/hematocrit, white blood count, T4 and TSH, and body mass index. Statistical analyses include RMANOVA, generalized estimation equation methodology and multiple regression analysis. Results may inform development of clinical guidelines for fatigue management during adjuvant CT. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FUNCTION OF CRYPTOCHROMES IN THE EYE Principal Investigator & Institution: Van Gelder, Russell N.; Assistant Professor; Ophthalmology and Visual Sci; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2001; Project Start 01-AUG-1999; Project End 31-JUL-2004 Summary: The candidate's long-term aims is to understand non-visual photoreception in the eye, and its relationship to modulation of circadian rhythmicity and ocular immune function. Retinal degenerate mice, although blind, retain functional ocular photoreception for two phenomena: the resetting of the behavioral circadian clock, and the modulation of ocular inflammation (ACAID). This finding suggests the existence of ocular photoreceptors outside rods and cones. The identity of the photoreceptor(s) underlying these phenomena are unknown, but as both phenomena share a common spectral sensitivity, a single photoreceptor molecule is implicated. A new family of flavin-based blue-light photoreceptors - the cryptochromes - have been described, and
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are expressed in the eye. These molecules have been implicated in the light-resetting of the circadian clock in plants, and are well conserved in mammals. Their role in the modulation of immune function or circadian rhythmicity in mammals is unknown. Identification of this phototransduction pathway has broad import in understanding both the ocular contributions to circadian rhythms and their disease states, such as insomnia and seasonal depression, and in understanding the mechanisms of pathogenesis of ocular inflammation. The candidate proposes to study the molecular biology and genetics of this protein family in the sponsor's laboratory. He will (1) determine the temporal and spatial expression of the cryptochromes in the murine eye and suprachiasmatic nucleus of the brain, (2) determine the gene structure of members of the cryptochrome family, and (3) generate loss- and gain-of-function mutations in the members of this family and study their effects on circadian rhythm entrainment and modulation of intraocular immune response. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FUNCTIONAL CHANGES INDUCED BY SLEEP DEPRIVATION Principal Investigator & Institution: Tononi, Giulio; Professor; Psychiatry; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2001; Project Start 15-MAY-2001; Project End 30-APR-2005 Summary: The functions of sleep constitute a genuine mystery in present day biology. Such functions can be investigated by preventing sleep from occurring. In rats, prolonged total or REM sleep deprivation lead to extreme sleepiness, weight loss, increase in food intake and metabolic rate, and death after 2-5 weeks. Decades of investigation have failed to reveal any substantial abnormality in peripheral organs or in the brain. Over the past few years, molecular approaches have been employed the to study the cellular correlates of sleep and waking. Several compounds have been shown to accumulate during waking and after short periods of sleep derivation and to return to basal levels during sleep, in line with homoeostatic models of sleep regulation. To evaluate the functional significance of these findings in the context of sleep homeostasis, new gene screening methods such as microarrays and differential display have been used to examine gene expression after both short-and long-term sleep deprivation. While most genes screened (approximately 10000) were not modified, the levels of brain arylsulfotransferase (AST) were increased by short periods of waking and even more so by prolonged sleep derivation. This enzyme is responsible for the inactivation of noradrenaline, which is released in the brain during waking and much less during NREM and REM sleep. The induction of AST may thus constitute a first indication of a homoeostatic response by the brain to the uninterrupted activity of the central noradrenergic system. This hypothesis will be tested by examining whether AST mRNA (1) progressively increases with the length of total sleep deprivation, increases after selective REM sleep derivation, and returns to normal after recovery sleep; (2) is accompanied by indices of increased central noradrenaline turnover; and (3) is reduced in animals with lesions of the central noradrenergic system. Finally, it will be established whether lesioned animals are more resistant to the harmful effects of sleep deprivation. These studies should provide insights into the molecular consequences of prolonged sleep deprivation and chronic insomnia and suggest new therapeutic approaches. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GABA RECEPTOR REGULATION BY SPLICING TRUNCATION Principal Investigator & Institution: Burt, David R.; Pharmacology; University of Maryland Balt Prof School Baltimore, Md 21201
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Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 30-APR-2006 Summary: (provided by applicant): The goal is to define the regulatory role of an unusual form of alternative splicing of GABAA receptor alpha4 subunits. GABA (gamma-aminobutyric acid) is the major inhibitory neurotransmitter in the brain. Its type A receptors, GABA-gated chloride channels, are the site of action of drugs used to treat alcohol withdrawal, epilepsy, insomnia, anxiety, etc., and are likely sites of action for alcohol itself. Many subunits (6 alpha, 3 beta, 3 gamma, delta, epsilon, pi, 3 rho, theta) have been cloned in mammals. The alpha4 subunit has been especially implicated in the actions of alcohol. The mRNAs for some subunits exhibit alternative splicing, further increasing subunit diversity. A puzzling form of splicing described for alpha5, alpha6, and rho1 subunits, where it is rare, creates short deletions in the bases coding for the N-terminal extracellular domain which make the resulting subunits nonfunctional. Recently we discovered a relatively common form of alternative splicing of the alpha4 subunit mRNA which, remarkably, creates a message missing everything except the first two coding exons and the last coding exon, with a frameshift between them. This pattern of splicing gives a severely truncated mRNA, not subject to nonsense-mediated mRNA decay, which codes for 2 possible proteins. A short piece of the N-terminus right after the signal peptide is the only one which seems to be made. The splicing is developmentally and regionally regulated. Electrophysiological data suggest that the truncated mRNA, when coexpresssed with the complete alpha4 subunit, selectively reduces currents due to the latter. We plan to explore further whether the truncated alpha4 protein plays a post-translational regulatory role in expression of GABAA receptors containing the alpha4 subunit. These studies may establish a novel and important mechanism of regulation of GABAA receptors responsive to alcohol. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GABA-ERGIC DRUGS--BEHAVIORAL AND ABUSE RELATED EFFECTS Principal Investigator & Institution: Paronis, Carol A.; Mc Lean Hospital (Belmont, Ma) Belmont, Ma 02478 Timing: Fiscal Year 2001; Project Start 30-SEP-1997; Project End 31-AUG-2003 Summary: (Applicant's Abstract) Benzodiazepines have remained the most commonly prescribed drugs for the treatment of caronic anxiety and insomnia since the 1960s. Chronic use of benzodiazepines is often associated with the development of physical dependence and addiction, particularly in populations with a history of drug or alcohol abuse. Concern regarding the public health consequences of benzodiazepine-related physical dependence and abuse liability has led to the recent development of novel benzodiazopine-like agonists with low intrinsic activity or with receptor-subtype selectivity. Yet, the complete pharmacological and behavioral characterization of these novel compounds is in its early stages. To meet the need for improved preclinical methods with which to study the dependence and abuse liability of these and fututre novel benzodiazpines, studies are proposed to evaluate the roles of agonist efficacy and selectivity in the development of tolerance to and dependence on benzodiazepine-like drugs. First, the acute agonist, antagonist, or partial agonist effects of different benzodiazepine-like drugs in monkeys will be quantitatively assessed using three established experimental procedures. Results of these experiments will be used to functionally categorize these drugs on the basis of efficacy and subtype selectivity. They also will provide an empirical foundation for subsequent studies. Second, the roles of efficacy and selectivity in the development of tolerance and dependence to benzodiazopine-like drugs will be studied in monkeys that are chronically exposed to
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full, partial or selective agonists. Full dose-effect functions for drugs differing in efficacy or selectivity will be determined during the different chronic treatments to provide information on how their behavioral effects arc thereby modified. The behavioral effects of nonbenzodiazepine GABAA modulators also will be examined to evaluate other changes in GABAA function that may result f om chronic benzodiazepine administration. The results of chronic studies will permit a quantitative analysis of the relationship between functional efficacy or receptor-subtype selectivity and the magnitude of tolerance and dependence that develops to benzodiazepine-like drugs. Overall, the proposed research will yield knowledge essential to understanding determinants of drug dependence in primates and predicting the addiction liability of novel benzodiazopine drugs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GHB TOLERANCE AND DEPENDENCE Principal Investigator & Institution: Kuhn, Cynthia M.; Professor; Pharmacology and Cancer Biology; Duke University Durham, Nc 27706 Timing: Fiscal Year 2003; Project Start 20-SEP-2003; Project End 31-MAY-2007 Summary: (provided by applicant): The purpose of this proposal is to investigate mechanisms of Gamma hydroxy butyrate (GHB) tolerance and dependence after chronic administration of low and high doses of GHB to rats. GHB is a novel sedative-hypnotic that is an emerging drug of abuse. GHB activates GHB, GABA-B and possibly GABA-A receptors, with a unique dose response relationship for each. When recreational users escalate use, tolerance develops and a withdrawal syndrome can occur that is characterized by insomnia, anxiety, and hallucinations. Tolerance and dependence to GHB are poorly characterized in animal models. We hypothesize that tolerance is related to dose and duration of exposure. We also hypothesize that the different receptor populations adapt at varying rates. We postulate that chronic treatment with lower doses or shorter regimens will cause tolerance at GHB and perhaps GABA-B receptors, while higher doses and longer treatments will lead to marked tolerance to GHB, GABA-A and GABA-B receptors. We will assess tolerance to GHB effects on sleep time, tilt plane and plus maze performance after chronic treatment with low or high doses for 7, 14 or 21 days. We will assess spontaneous and GHB (NCS-382) and GABA-B (CGP46381) antagonist-precipitated withdrawal by measuring sleep-wake cycle, locomotion as well as blood pressure and heart rate. Cross-tolerance to GABA-B (baclofen) and GABA-A (pentobarbital, diazepam) agonists will be assessed with the same behavioral measures. We will characterize inhibitory GHB mechanisms using electrophysiologic techniques in frontal cortex. GHB effects on spontaneous, evoked and mini GABA-A IPSCs and on postsynaptic potassium conductance will be determined. The effects of low and high GHB concentrations will be contrasted, and blockade by NCS-382 and CGP46381 on all parameters will be determined. Tolerance to specific GHB and GABA-B mechanisms will be studied by evaluating the same parameters in frontal cortex slices from animals treated chronically with low or high dose GHB. Finally, we will assess GHB effects on GABA-A receptors in naive and tolerant animals by measuring effects on GABA-mediated C1 uptake into synaptoneurosomes and its modulation by benzodiazepines, barbiturates and neurosteroids. These experiments should ultimately lead to the development of more effective pharmacotherapies for GHB dependence, which is an emerging drug abuse problem. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HIGH TECH/LOW COST HOME TREATMENT FOR GERIATRIC INSOMNIA Principal Investigator & Institution: Alsten, Christopher R.; Inner Health, Inc. 1260 Lincoln Ave San Diego, Ca 92103 Timing: Fiscal Year 2001; Project Start 01-DEC-1998; Project End 31-MAY-2003 Summary: This study will test the efficacy of a technology-enhanced home behavioral treatment (THBT) or older adults with insomnia and comorbid chronic illness. The SBIR 1 study found that THBT yielded short-term reductions in insomnia compared to no treatment. These benefits were comparable to those obtained from a classroom treatment at much less cost. The goal of the proposed study will be extend these findings using a more precise methodology, measurement of longer-term benefits, and comparison to an alternative self-help treatment. Subjects will include 80 older adults with one of two common chronic diseases with high rates of comorbid insomnia: osteoarthritis and coronary artery disease. They will receive one of the two treatments: THBT with video instruction on cognitive-behavioral (CB) techniques and 3-D audio relaxation training; or bibliotherapy treatment using a previously tested CB self-help book. Outcomes will be assessed at post-treatment and 1 year follow-up using objective and self-report measures of sleep. Quality of life, functional status and health care utilization benefits will be assessed. This study complements an R01 proposal by the coinvestigators which includes a classroom CB treatment and a placebo treatment, thus allowing for outcome comparisons across a continuum of behavioral treatment modalities. An easy-to-use home treatment package would have strong potential as a first-line treatment for geriatric insomnia. PROPOSED COMMERCIAL APPLICATION: Not available Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HYPOCRETINS AND THEIR ROLE IN THE CONTROL OF SLEEP Principal Investigator & Institution: Maki, Richard A.; Senior Staff Scientist; Neurocrine Biosciences, Inc. 10555 Science Center Dr San Diego, Ca 921211100 Timing: Fiscal Year 2001; Project Start 15-SEP-2001; Project End 31-AUG-2003 Summary: DESRIPTION: (Adapted from the Applicant?s Abstract) Insomnia is one of the more prevalent sleep disorders in the US, affecting about 10 percent of the population. Other sleep disorders include obstructive sleep apnea, restless leg syndrome and narcolepsy. Recently, a mutation in the G-protein coupled receptor hypocretin receptor-2 has been linked to the development of narcolepsy in dogs. In addition, the disruption of a gene in mice for the neuropeptide hypocretin led to the development of narcolepsy in those mice. These two results have focused attention on the hypocretin system as an important modulator of sleep in humans. The applicant organization, Neurocrine Biosciences, has developed a series of small molecule antagonists to the hypocretin receptor-2. The focus of this application is to first characterize these small molecule antagonists in vitro. The antagonists will be tested in competitive binding assays and cell-based functional assays. Second, the small molecule antagonists will be tested in vivo. Both rat and dog models will be set up and evaluated for the effect of the small molecule antagonists on sleep and wakefulness. The specificity of the effects of the small molecule antagonists will be further evaluated by comparing normal dogs with hypocretin receptor-2 mutated narcoleptic dogs. The results of this study will be valuable in determining the effectiveness of a hypocretin receptor antagonist in the control of sleep. These studies will also help to prepare the groundwork for the future development of hypocretin receptor-2 agonist as a possible treatment for narcolepsy.
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PROPOSED COMMERCIAL APPLICATION: A potential application for the research proposed is in the field of insomnia (an estimated 10% of the population suffers from chronic insomnia). Based on the available data, it is reasonable to hypothesize that hypocretin receptor antagonists will promote non-REM and REM sleep. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HYPOTHALAMIC REGULATION OF SLEEP Principal Investigator & Institution: Shiromani, Priyattam J.; Associate Professor; Neurology; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2001; Project Start 13-SEP-1997; Project End 30-JUN-2006 Summary: (provided by applicant): Human narcolepsy was recently associated with a decline in orexin/hypocretin containing neurons. These neurons are located only in the lateral hypothalamus, a region not previously implicated in narcolepsy or REM sleep. How could destruction of these cells lead to narcoleptic behavior? One way to answer this question would be to determine whether lesion of the target neurons produces narcoleptic symptoms. However, there are no studies demonstrating which hypocretin/orexin innervation to what target area regulates which aspect of sleep-wake behavior. To target the cells which express the hypocretin/orexin receptors in adult animals, we have conjugated the ribosome inactivating protein, saporin, to hypocretin2/orexin B. We will utilize the orexin-saporin to test the overall hypothesis that hypocretin/orexin via its innervation of specific targets promotes wakefulness and inhibits REM sleep. Specific aim 1 will test the hypothesis that orexin/hypocretin innervation to the dorsolateral pons regulates REM sleep and cataplexy. Historically, the dorsolateral pontine area has been implicated in regulating REM sleep. Since narcoleptic canines and the orexin gene knockout mice show cataplexy and rapid onset of REM sleep, destruction of the hypocretin/orexin-receptor containing neurons should result in cataplexy and REM sleep. Specific aim 2 will test the hypothesis that the orexin/hypocretin neuronal innervation of the TMN is important for wakefulness. Since narcoleptics are excessively sleepy, it is possible that the hypocretin/orexin influence on wakefulness may come via innervation of neurotransmitter containing populations such as the TMN, LC and basal forebrain. Specific aim 3 will examine the effects of orexinsaporin applied to the basal forebrain on sleep and wakefulness. Besides the TMN, wake-active neurons located in the basal forebrain are also hypothesized to promote wakefulness, and hypocretin/orexin fibers innervate this region. It is also hypothesized that degenerating axon in this region might underlie the emotional triggering of cataplectic attacks in narcolepsy (Siegel et al., 1999). Since application of orexin-saporin destroys orexin-receptor bearing neurons, this is an excellent method that can be used to evaluate the degenerating axon hypothesis. Specific aim 4 will examine the effects of orexin-saporin applications to the VLPO-preoptic area. In the previous cycle we demonstrated that lesions of the sleep-active cells in VLPO produce long-lasting insomnia. Since hypocretin/orexin fibers innervate this area it is necessary to determine whether orexin-saporin administered to the VLPO produces long-lasting hypersomnia. Specific aim 5 will determine the effects of the orexin-saporin on neurons containing the hypocretin-1 versus hypocretin-2 receptors. This will determine which receptor subtype containing neurons are affected by the saporin conjugate. Our findings will provide a framework for integrating the hypocretin/orexin cells within an overall model of sleep regulation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: IDENTIFICATION AND ANALYSIS OF CLOCK CONTROLLED GENES Principal Investigator & Institution: Dunlap, Jay C.; Professor; Biochemistry; Dartmouth College 11 Rope Ferry Rd. #6210 Hanover, Nh 03755 Timing: Fiscal Year 2001; Project Start 01-SEP-1989; Project End 31-DEC-2002 Summary: (Adapted from applicant's abstract): Virtually all eukaryotic organisms appropriately examined have been shown to possess the capacity for endogenous temporal control and organization known as a circadian rhythm. The cellular machinery responsible for generating this ability is collectively known as the biological clock. The importance of a detailed understanding of the circadian clock to our understanding of physical and mental health and the treatment of mental illness rests on the ubiquity of its influence on human mental and physiological processes. These range from circadian changes in basic physiological functions to the clear involvement of rhythms in human work rest cycles and sleep. Human psychiatric illnesses known to be a direct result of clock malfunction include common forms of manic-depressive illness and insomnia. Extensive research has demonstrated the significance of clock control of gene expression, but little is known regarding how clocks control the behavior of the cells in which they operate. One salient aspect of this regulation is clock control of mRNA abundance. We have identified "ccg" genes that are unequivocally under circadian clock control, and we are now using genetic and biochemical approaches to identify the cisand trans-acting factors conferring clock regulation. In Specific Aim 1 we will complete the identification of the trans-acting factors that mediate clock-controlled activation and repression of downstream genes. We have identified several novel ccgs including a gene, ccg-9, required to mediate clock regulation of downstream genes. In Specific Aim 2 we will determine the identity of novel ccgs and will study the mode of action of CCG9, in particular, to understand how it mediates clock regulation and how it is regulated by factors in or next to the oscillator. We have developed a strong conceptual base in genomics and have begun the elucidation, via high through-put sequencing, of the global morning versus evening gene expression pattern in a simple cellular oscillator. Further, we now understand in broad outline how the clock works, what some clock genes look like, and enough about what characterizes their behavior that we can evaluate novel genes in a new system. In Specific Aim 3 we will (1) clone and characterize additional clock genes, (2) complete the identification of morning versus evening genes in Neurospora, and (3) extend this technology to a more complex cellular oscillator in a mammalian system by examining morning versus evening gene expression in the mouse SCN. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ILLUMINATION IN HUMAN AGING: SLEEP AND MOOD EFFECTS Principal Investigator & Institution: Kripke, Daniel F.; Professor of Psychiatry; Psychiatry; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 92093 Timing: Fiscal Year 2001; Project Start 30-SEP-1994; Project End 30-APR-2005 Summary: (adapted from investigator's abstract): Most older Americans are troubled by low-level depression or sleep disturbances, which are often intimately intertwined. In the first 5 years of AG12364, they have been examining the etiologies of depression and insomnia in aging volunteers. Their findings suggest an appalling degree of circadian malsynchronization among aging Americans, which possibly explains part of their insomnia and low mood. Further, their volunteers displayed surprisingly weak
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circadian and clinical responses to 4 days of bright light treatment, indicating possible light resistance. In this renewal, they will test more extended 4-week bright light treatments in the home, to determine if light resistance in volunteers ages 60-79 years can be overcome with a longer duration of treatment. One hundred fifty volunteers with significant depressive complaints will be recruited for a trial consisting of one-week placebo baseline terminating in a half-night sleep deprivation, followed by 4 weeks randomized assignment to 10,000 lux white light or 10 lux red light placebo. Phasetyping during baseline will determine before randomization whether treatment should best be given in the morning, mid-day, or evening. Fractional urine samples for 6sulphatoxymelatonin will be collected for 48 hours at the end of baseline and for 48 hours at the end of the randomized treatment, to determine if 10,000 lux treatments successfully normalize malsynchronized circadian phase adjustments. The success of the treatment in lowering the GDS depression score and in reducing sleep complaints will be examined. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IMPACT OF SLEEP DISORDERS ON HEALTH Principal Investigator & Institution: Kryger, Meir H.; University of Manitoba Winnipeg R3t 2N2, Canada Winnipeg, Timing: Fiscal Year 2001; Project Start 01-APR-2000; Project End 31-MAR-2003 Summary: Sleep disorders are very common. The impact of these disorders on a person's long term health is unclear. The purpose of this project is to determine the cost to the health care system of patients with untreated sleep disorders and then to determine the change in cost with diagnosis and treatment. Hypotheses: Untreated sleep disorder patients (with sleep apnea, narcolepsy, and insomnia) are heavier consumers of health care services than age and sex matched controlled subjects and treatment will reduce these costs. Aims: The applicant will examine healthcare utilization data (and what patients were being treated for) of a large number of patients five years before diagnosis and five years after diagnosis and compare them to controls matched by age, gender, and postal code. The data will be obtained in a community with unrestricted access to medical care and where all the data is stored on a central database. To measure the use of medical services the applicant will analyze all doctors' claims and data from all hospitalization as well as use of prescription drugs. The applicant will establish whether treatment of these disorders reduces the consumption of healthcare services in these patients. The applicant expects to find fewer physicians visits, particularly for cardiovascular disease, neuro-psychiatric disease and general medical evaluations and for sleep apnea, fewer hospitalizations, particularly for cardiovascular disease and respiratory failure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: INSOMNIA AS A PATH TO ALCOHOL ABUSE Principal Investigator & Institution: Roehrs, Timothy A.; Director of Research and Academic Appoin; Psychiatry; Case Western Reserve Univ-Henry Ford Hsc Research Administraion Cfp-046 Detroit, Mi 48202 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 31-MAR-2006 Summary: Chronic insomnia is reported by 10% of the general population and clearly has morbidity associated with it. But, it is often left untreated medically and a large percentage of people with insomnia (40%) self- medicate using over-the-counter (OTC) medications and alcohol, with 67% of those using alcohol reporting it was effective. This
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research program seeks to understand the risks associated with the use of ethanol as a hypnotic. There now is information that initially ethanol at low doses (i.e., doses insomniacs in the general population report using) improves the sleep of persons with insomnia and further, insomniacs self administer (SA) low ethanol doses at bedtime (i.e., as a hypnotic) to a greater extent than non-insomniacs with similar social drinking histories. The working hypothesis of this proposal regarding the risks of hypnotic ethanol use in the insomniac is that, while sleep is initially improved with ethanol, it's beneficial effects diminish rapidly and with "hypnotic" use of ethanol the insomniac finds its "mood-altering" effects reinforcing, thus leading to increased nightly ethanol intake extending beyond the hypnotic context and occurring in the absence of hypnotic effects. In other words, what may initially be sleep-medicating behavior, then becomes "mood-altering" behavior that begins to demonstrate some of the characteristics of drugseeking behavior (i.e., alcoholic drinking). This proposal outlines three experiments to be conducted over the five year grant period. The studies are designed to explore each of three drug-seeking characteristics: dose escalation, enhanced daytime ethanol SA, and nightly SA in the absence of hypnotic effects. In the three studies attempts will be made to determine whether sleep effects, mood effects, or both determine the reinforcing function of ethanol for the insomniac and how those effects may change over time with prior exposure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INSOMNIA CLASSIFICATION PROJECT Principal Investigator & Institution: Edinger, Jack D.; Clinical Professor; Psychiatry; Duke University Durham, Nc 27706 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-APR-2008 Summary: (provided by applicant): Clinicians and researchers have long recognized that chronic insomnia arises from varied causes including primary sleep disorders, medical diseases, psychiatric illnesses, medication/substance abuse, and a host of behavioral and environmental factors. This recognition, in turn, has highlighted the need for a classification system to aid communication, structure diagnostic practice, and ultimately guide treatment decision-making among those who care for insomnia patients. Unfortunately, notable controversies over the nature and number of insomnia subtypes needing definition and the methods whereby insomnia diagnoses should be established have led to the emergence of two distinctive insomnia nosologies. One system, presented in the DSM-IV, postulates a limited number of global insomnia subtypes and advocates reliance on the clinical interview for diagnostic ascertainment. The other, presented in the International Classification of Sleep Disorders (ICSD), delineates many more highly specific insomnia subtypes and encourages consideration of sleep laboratory data in deriving diagnoses. Despite each of these system's fervent supporters, large prospective studies to test the reliability and validity of these nosologies and the diagnostic methods they encourage have yet to be conducted. The project proposed entails a prospective, dual-site investigation with a sizable (N = 448) research cohort designed to: (1) ascertain and compare the reliability and validity of the subtypes these two nosologies delineate; and (2) evaluate the contribution of sleep lab (polysomnographic - PSG) findings on the pattern of diagnoses assigned. The primary research methodology will consist of a multitrait-multimethod strategy in which three experienced clinician dyads derive DSM-IV and ICSD insomnia diagnostic impressions either through structured interviews, unstructured clinical interviews, or unstructured interviews combined with PSG findings. A resulting multitrait-multimethod matrix will be established for each nosology to evaluate the reliability, convergent validity, and
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discriminant validity of its various insomnia subtypes. In addition, all participants will complete a comprehensive psychometric battery and structured psychiatric interview (SCID) shortly after study enrollment to assess the concurrent validity of the DSM-IV and ICSD diagnostic subtypes. This project will provide a much-needed comparison of these two insomnia nosologies and the subtypes they define. Results also likely will provide important information for future insomnia classification efforts. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INSOMNIA INTERVENTION FOR BREAST CANCER SURVIVORS Principal Investigator & Institution: Epstein, Dana R.; None; Arizona State University P.O. Box 873503 Tempe, Az 852873503 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): Insomnia is the most common sleep disorder in both the general population and persons with cancer. Many of the sleep characteristics and ineffective insomnia management strategies of patients with cancer are similar to those of persons with insomnia in the general population. Although women with breast cancer appear to have about twice the risk of developing clinically significant levels of insomnia, sleep difficulty has received minimal treatment attention other than pharmacological intervention (e.g. sedatives/hypnotics, antidepressants). There is a paucity of intervention studies addressing the feasibility and efficacy of nonpharmacological treatment for patients most at need and at risk such as breast cancer survivors (BCS). latrogenic, psychological, and developmental factors may contribute to the development of insomnia in BCS and must be considered in the construction and testing of cognitive-behavioral treatment (CBT). The purpose of the study is to pilot test the feasibility (attendance, attrition, adherence to treatment, participant evaluation of treatment) of a multicomponent CBT and the efficacy of CBT for reducing insomnia in BCS. A 2 (group) X 2 (measurement phase) factorial design will be used. Sixty-four breast cancer survivors will be blocked on their type of insomnia (primary or secondary) and randomly assigned within each type of insomnia to one of the two conditions: CBT group or a contact control group. After the screening process, subjects will be assessed at pre-treatment, treatment, and post-treatment. Sleep outcomes will be evaluated using objective (wrist actigraphy) and subjective (daily sleep diaries) measures. In addition, the impact of CBT on the sleep-associated variables of fatigue, mood, and quality of life will also be explored. Descriptive statistics, analyses of covariance, mediational analysis, and regression analysis will be used to examine the data. This feasibility pilot study will provide the basis for a larger study to evaluate efficacy and to examine the effect of the intervention on the quality of survival time and comorbidities among BCS. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: K+-CHANNELS REGULATING REM-RELATED CHOLINGERGIC NEURONS Principal Investigator & Institution: Leonard, Christopher S.; Profesor; Physiology; New York Medical College Valhalla, Ny 10595 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-AUG-2003 Summary: How and why we sleep are central unsolved questions in medicine. Nearly 40 million people in the United States are estimated to experience chronic or intermittent sleep disorders such as narcolepsy, sleep apnea, restless leg syndrome and insomnia. Traditional approaches have identified several neuronal populations whose interplay is
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important in generating sleep and wakefulness. How that interplay is established, how it is altered and its cellular and molecular consequences, remain poorly understood. The long-term objective of this proposal is to determine the molecular identity and function of ion channels and receptors expressed by sleep-related neurons in order to understand the molecular mechanisms controlling sleep generation. This application focuses on the identity and function of a family of K+ channels subunit genes in controlling activity of mesopontine cholinergic neurons which are believed to play a pivotal role in the generation of wakefulness and REM sleep. Our central hypothesis is that K+ channels formed by Kv3 subunits regulate action potential shape, intracellular Ca2+ levels, repetitive firing and the release of transmitter from mesopontine cholinergic neurons. To test this hypothesis we will use pharmacological methods with whole-cell patch clamp recordings in brain slices from wild-type and Kv3 knock-out mice. The results of these studies will 1) identify and verify the intrinsic electrophysiological properties of important REM-sleep related neurons in mouse; 2) determine the molecular identity and function of native K+ channels formed by Kv3 subunits; 3) elucidate new mechanisms controlling the activity and release of transmitter by REM sleep-related neurons; 4) identify novel functions of Kv3 channels which have previously been associated with the fast-spiking phenotype rather than broad-spiking phenotype of brainstem cholinergic neurons. These results will contribute to our understanding of the molecular basis of sleep regulation as well as advancing the mouse as a platform for future sleep research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: LUMINAIRE FOR SLEEP AND MOOD DISORDERS OF AGING Principal Investigator & Institution: Savage, Henry C.; Apollo Light Systems, Inc. 352 West 1060 South Orem, Ut 84058 Timing: Fiscal Year 2001; Project Start 01-JUL-1998; Project End 31-MAY-2002 Summary: Most older Americans are troubled by insomnia or low-level depression, which are often intimately intertwined, causing enormous disability and economic loss. Available treatment methods for these often-chronic conditions have been unsatisfactory. Insomnia and depression in the elderly may be partly due to circadian rhythm malsynchronization preventable by improved lighting. Apollo Light Systems, Inc. has developed a special Senior's Luminaire (a floor lamp) to reduce sleep and mood problems of aging Americans. In Phase I, investigational prototypes at 3 different brightness levels were tested in the homes of volunteers over age 60 years. Volunteers reported the Senior's Luminaires reduced insomnia and depression, and wanted to continue using them. Acceptance and efficacy of the Phase I prototypes was remarkably encouraging. In this Phase II STTR proposal, Apollo Light Systems will construct an improved series of Senior's Luminaire prototypes. New prototypes will be evaluated in 60 aging volunteers to demonstrate the efficacy of the Senior's Luminaire contrasted with placebo luminaires. The project will demonstrate that the Senior's Luminaire reduces insomnia and improves mood. Biological efficacy for shifting advanced circadian rhythms will be demonstrated by analyzing urinary 6-sulphatoxymelatonin. There is a potential market for millions of improved luminaires to improve the lives of aging Americans. PROPOSED COMMERCIAL APPLICATION: Over 10,000,000 aging Americans have symptoms of insomnia or depression which might be reduced by the Seniors' Luminaire. The potential market is demonstrated by sale of over 40,000,000 halogen torchiere lamps, considering that the Seniors' Luminaire provides 7 times more light with less than 25% the energy cost. It is a superior design which might be purchased for tens of millions of American homes.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MANAGEMENT OF CANCER-RELATED FATIGUE AND SLEEP QUALITY Principal Investigator & Institution: Barsevick, Andrea M.; Director of Nursing Research and Educati; Fox Chase Cancer Center Philadelphia, Pa 19111 Timing: Fiscal Year 2003; Project Start 15-FEB-1999; Project End 31-JAN-2007 Summary: (provided by applicant): An important shift is now occurring in symptom management research to examine symptom clusters rather than single symptoms. The overall aim of the proposed research is to extend our scientific understanding of symptom management by examining the effect of an intervention for two target symptoms commonly reported during cancer treatment, fatigue and insomnia. We will also examine the effect of the intervention on two related symptoms, pain and depression, that are not targeted by the intervention. The investigators will extend the science through the design that allows us to test hypotheses about the added value of targeting insomnia, as well as fatigue, and about the process that underlies the clustering of the target and related symptoms. The specific aims of the proposed research are to: 1) test the efficacy of a combined fatigue/sleep intervention on the target symptoms of fatigue and insomnia and on functional performance; 2) examine the degree to which improved sleep quality mediates the effect of the intervention on fatigue; 3) examine the relationships among fatigue, insomnia, pain, depression, and functional performance to generate hypotheses about the processes underlying clustering of these commonly reported symptoms during cancer treatment. The proposed research will use an experimental design to compare an individual management plan for fatigue/sleep with a control group that equates for time and attention. The study will be implemented in two clinical sites including an academic health science center (Barrett Cancer Center of the University of Cincinnati) and a comprehensive cancer center (Fox Chase Cancer Center in Philadelphia). Participants will be randomly assigned to the intervention or the control group. The major outcomes of interest include the target symptoms of fatigue and insomnia and the related symptoms of pain and depression. In addition, functional performance, a dimension of quality of life, will be evaluated. The investigators will use traditional repeated measures ANOVA to test the efficacy of the intervention. Multiple regression analysis will be used to test the mediation hypothesis in which the relationship between the intervention and fatigue is partially accounted for by the improvement in sleep quality due to the intervention. Multiple statistical techniques will be used to develop and explore models that could explain covariation among symptoms that are seen as clusters. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MELATONIN ANALOG FOR SLEEP DISORDERS Principal Investigator & Institution: Mulchahey, James J.; Assistant Professor; Phase 2 Discovery, Inc. 3130 Highland Ave, 3Rd Fl Cincinnati, Oh 45219 Timing: Fiscal Year 2002; Project Start 12-SEP-2002; Project End 31-DEC-2002 Summary: (PROVIDED BY APPLICANT): Phase 2 Discovery is developing a synthetic melatonin analog (PD6735) for the treatment of sleep disorders. PD6735 is being developed as a safe and effective treatment for sleep disorders that lacks the side effects of current first-line sleep medications. Initial clinical studies indicate that PD6735 is safe and well tolerated in humans through the maximal dose tested, 20 mg. PD6735
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produced a dose-response improvement in sleep latency in subjects with sleep onset insomnia (double-blind, placebo controlled, crossover study, N=1 9). The PD6735 effect on sleep latency was more pronounced at 20 mg than at 5 mg. The goal of the present Fast Track application is to determine whether the dose-response effect of PD6735 on sleep latency will be more pronounced at higher PD6735 doses. Phase 1 of this proposal will establish the safety and tolerability of PD6735 at 20 to 100 mg doses. Phase 2 will determine the effect of the 20 to 100 mg doses (or the maximum safe P 06735 dose identified in Phase I) on sleep latency in subjects with sleep-onset insomnia. The Specific Aims of the Phase 1 portion of this proposal are: Aim I: Evaluate the safety and tolerability of PD6735 at doses up to 100 mg. Oral doses of 20, 35, 50 and 100 mg will be employed. Aim 2: Determine the pharmacokinetics of PD6735 at doses up to 100 mg. Aim 3: Determine the pharmacodynamics of PD6735 at doses up to 100 mg. PD6735 effects on body temperature and subjective sleepiness will be evaluated. PROPOSED COMMERCIAL APPLICATIONS: Sleep disorders affect over 60 million Americans who spend more than $1.4 billion on sleep medications would have a competitive advantage over current first line therapies by virtue of possessing fewer side effects. As such, the melatonin analog should capture a substantial portion of this market. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
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 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
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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: MELATONIN, BEHAVIOR AND NEURONAL ACTIVITY IN ZEBRAFISH Principal Investigator & Institution: Zhdanova, Irina V.; Research Associate Professor; Anatomy and Neurobiology; Boston University Medical Campus 715 Albany St, 560 Boston, Ma 02118 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2007 Summary: (provided by applicant): The long-term goal of our studies is to identify the mechanisms mediating the physiological effects of melatonin on human sleep and circadian rhythms, and to apply this knowledge to designing new therapeutic strategies for insomnia. Our recent studies have established that rest state in diurnal genetically well-characterized lower vertebrate, zebrafish, has critical behavioral similarities with sleep and that melatonin can promote a sleep-like state in zebrafish via specific melatonin receptors. The goals of the proposed project are to determine the contribution of overnight melatonin receptor activation by endogenous melatonin to quantitative parameters of nighttime sleep-like state and the circadian rhythm of activity in zebrafish, to identify melatonin receptor subtypes responsible for sleep and circadian modulation, and to identify the reticulospinal neurons mediating locomotor effects of melatonin treatment. The effects of melatonin on sleep-like state and circadian rhythm parameters will be assessed in wild-type and melatonin receptor knockdown larval zebrafish using: i) high throughput automatic image analysis system for locomotor activity recordings; ii) melatonin receptor ligands with different affinity to melatonin receptor subtypes and inhibition of melatonin synthesis; iii) knockdown of melatonin receptor subtypes with antisense morpholino oligonucleotides; iv) in vivo confocal calcium imaging for monitoring spontaneous and evoked activity of individual neurons during high-speed recordings of larval locomotor behavior; v) laser ablation of candidate neurons under confocal microscope, followed by behavioral evaluation. These studies would clarify the role of endogenous melatonin in sleep regulation in the diurnal vertebrate, characterize functional specificity of melatonin receptors and role of reticulospinal neurons in locomotor effects of melatonin. They would also constitute a background for the identification of neuronal networks and intracellular signaling pathways mediating the effects of melatonin on sleep-like state and circadian rhythmicity. Furthermore, a continuation of these studies on the physiological regulation of the sleep-like state in zebrafish, in conjunction with the availability of multiple zebrafish mutants and a complete sequence of zebrafish genome soon to be available, could potentially lead to a better understanding of the genetic basis of sleep regulation and sleep function in vertebrates. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MELATONIN-LIGHT INTERACTION ON CIRCADIAN ACTIVITY Principal Investigator & Institution: Dubocovich, Margarita L.; Professor; Mol Pharm & Biol Chemistry; Northwestern University Office of Sponsored Programs Chicago, Il 60611 Timing: Fiscal Year 2001; Project Start 01-MAY-1996; Project End 30-JUN-2004
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Summary: (applicant's abstract): Our long term goal is to understand the molecular, biochemical, signaling and functional properties of melatonin receptor subtypes in the mammalian central nervous system and to determine the role of this hormone in regulating the transmission of visual and circadian information. The overall goal of the present application is to elucidate the cellular and functional mechanism(s) through which activation of G-protein linked melatonin receptor subtypes (mt1 and MT2) and putative nuclear melatonin receptors (ROR-beta) within the circadian timing system (retina, SCN and IGL) affects circadian rhythms, regulates the entrainment of circadian rhythms following alterations in the light/dark cycle and modulates light responses reaching the circadian timing system. The experiments proposed in this application make use of new advances in the field of melatonin receptor research that occurred since the last submission. This includes the cloning of new mammalian melatonin receptor subtypes (mt1(Mel1a), MT2(Mel1b)], the discovery of specific and selective MT2 melatonin receptor antagonists as well as the establishment of mice lines with disruption of the mt1 melatonin receptor gene or the putative nuclear melatonin receptor gene, ROR-beta. The use of these probes and animal models permits to investigate the localization of melatonin receptor subtypes within the mammalian timing system, to establish their functional role in the regulation of circadian responses and interaction with light and to assess the consequence of their activation on signaling and gene regulation. We will address the following specific aims: 1) to determine within the circadian timing system the cellular localization of melatonin receptor subtypes (mt1 and MT2) and colocalization with the nuclear receptor ROR-beta, glutamate receptors (NMDA, AMPA, metabotropic), and per genes (per1, per2, per3); 2) to determine the melatonin receptor type involved in melatonin-mediated phase shifts of circadian rhythms and the signal transduction pathways altering clock activity in vitro; 3) to assess the receptor subtypes and mechanism(s) of light-melatonin interaction leading to advances in the phase of the clock; 4) to assess the mechanism(s) by which melatonin affects the rate of reentrainment following an abrupt phase advance of the dark cycle. The results of these studies will allow the rational design and synthesis of subtypes selective melatonin receptor agonists and antagonists that when administered at specific times will lead to either advances or delays of the clock. These novel therapeutic agents could be used for the treatment of insomnia or circadian disturbances involving abnormal phase advance (Advanced Sleep Phase Syndrome, endogenous depression, east jet flight) or phase delays (Delayed Sleep Phase Syndrome; seasonal affective disorders, west jet flight). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MENOPAUSE AND MIDLIFE AGING EFFECTS ON SLEEP DISORDERS Principal Investigator & Institution: Young, Terry B.; Professor of Prventative Medicine; Preventive Medicine; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2001; Project Start 15-JAN-1997; Project End 31-DEC-2001 Summary: A marked increase in the prevalence of sleep apnea, insomnia and hypersomnia in women has been noted during mid-life aging. Despite these observations and the biologic rationale that menopausal changes are likely to profoundly affect sleep, research on the pathogenesis of sleep disorders in women as they pass through menopause is lacking. The long-range goals of this longitudinal study of mid-life aging in women are to understand the role of menopause in the occurrence and progression of sleep apnea, insomnia and hypersomnolence and ultimately to
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formulate clinical strategies for intervention and prevention of the increased risk of theses dyssomnias in mid-life. Understanding the role of menopause in dyssomnia occurrence is particularly important because millions of women are exposed to menopausal changes yearly and because the hypothesized outcomes, particularly sleep apnea, are associated with cardiovascular and behavioral morbidity and mortality. The results of this study will have direct application o medical care for women in mid-life. The proposed study is designed to (1) definitively test the hypothesis that sleep apnea, insomnia and hypersomnia incidence and progression increase in peri and post menopause, relative to premenopause; (2) test the hypothesis that the association of sleep disorders and mid-life aging is attributable to menopause-related changes in body habitus; (3) test the hypothesis that peri and post menopausal women with hormonal replacement therapy, relative to those without, have lower incidence of dyssomnias; (4) determine the effect of type of menopause on dyssomnia occurrence in mid-life, and (5) establish a cohort of 150 women with data on menopausal status to be merged with ongoing data collected by the parent study on functional status, health care costs, cardiovascular and behavioral outcomes for future analyses. A robust prospective longitudinal study design with adequate power to address the above specific aims will be used. Semiannual home polysomnography studies and other measurement of dyssomnia during peri and post menopause will be conducted on a cohort of 150 women on whom up to 8 years of polysomnography data during premenopause have already been collected as part of the parent study, the Wisconsin Sleep Cohort Study. The specific aims, will be addressed using standard definition of menopause and dyssomnias, with longitudinal multivariate models able to control for confounding factors and to investigate interactions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR STUDIES OF HUMAN AND ANIMAL PRION PROTEINS Principal Investigator & Institution: Chen, Shu G.; Associate Professor; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2007 Summary: GRANT=6546043;P01AG Prion diseases are a group of fatal and transmissible neurodegenerative disorders affecting both humans and animals. They include Creutzfeld-Jakob disease (CJD), Gerstmann-Straussler-Scheinker syndrome, and fatal familial insomnia in humans, and scrapie, chronic wasting disease (CWD) and bovine spongiform encephalopathy (BSE) in animals. A wealth of data supports a causal role for an abnormal, protease-resistant isoform of the prion protein, PrP-Sc, in the pathogenesis of prion disease. The possibility of disease transmission between animals and humans has recently been highlighted due to the occurrence in young adults of a new variant form of CJD (vCJD) that is thought to originate rom BSE in cattle. The longterm objective of the present project is to understand the structural basis by which PrPSc modulates disease phenotypes in humans and animals, and in transmission of prion diseases from animals to humans. Toward this end, this project is focused on the following specific aims. Specific Aim 1 will focus on a systemic comparison of all PrP-Sc subtypes in human and animal prion diseases. The sensitive and rapid PrP-Sc typing method developed in our laboratory will be used for the detection of all variants of PrPSc in humans and animals using Western blot analysis. Cases from human prion diseases include CJD of various phenotypes, FFI and GSS. The animal cases will be BSE of cattle, CWD in deer and elk, and experimental scrapie prion stains. Both conventional and two-dimensional gel electrophoresis will be used to separate different PrP-Sc
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subtypes and provide a comprehensive map of protein subtypes. Specific Aim 2 will characterize the protease cleavage sites of PrP-Sc in human and animals to determine conformational variabilityof PrP-Sc. Purified PrP-Sc from diseased brains will be used to analyze the protease cleavage sites using multiple approaches such as N-terminal sequencing, enzymatic digestion, HPLC, and mass spectrometry. Specific Aim 3 will examine the glycosylation patterns of PrP-Sc in human and animal brains since N-linked glycosylation contributes to the structural stability and heterogeneity of PrP-Sc. Purified PrP-Sc preparations will be denatured and trypsinized to allow isolation and purification by HPLC of glycopeptides containing N-linked glycosylation sites. The glycan structures will be determined by liquid chromatography and tandem mass spectrometry. In Specific Aim 4 the secondary structure of purified animal and human PrP-Sc will be examined and compared using Fourier transform infrared spectroscopy. These proposed studies will lead to a better understanding of the role of the PrP-Sc structures in pathogenesis and transmission of prion disease. 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 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
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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: NEW TECHNOLOGY AND OUTREACH IN SLEEP EDUCATION Principal Investigator & Institution: Sateia, Michael J.; Associate Professor; Psychiatry; Dartmouth College 11 Rope Ferry Rd. #6210 Hanover, Nh 03755 Timing: Fiscal Year 2001; Project Start 01-SEP-1998; Project End 30-AUG-2003 Summary: Sleep disorders represent a major public health problem, affecting at least 1520% of the U.S. population on a chronic basis, and an even larger number intermittently. These disorders result in significant mortality, morbidity, and impairment in productivity and quality of life. Most of these disorders are diagnosable and treatable. However, a serious misunderstanding of the primary symptoms of these disorders, particularly insomnia and sleepiness, by both physicians and the general population, result in failure to properly identify these conditions as medical disorders. Furthermore, physicians frequently lack the knowledge to conduct basic evaluations even when the condition is brought to their attention. This proposal puts forth a multi-faceted program of curriculum development and implementation, public health education, and design of new educational strategies in order to address these challenges. The goal of this proposal is not only to impart knowledge but also to alter physician and patient attitudes and behavior with respect to identification and treatment of sleep disorders. These goals will be accomplished by: 1) Introduction to issues of sleep and circadian rhythms at the undergraduate level in an effort to stimulate interest in this field and encourage careers in sleep medicine; 2) Development of formal pre-clinical and clinical curricula for undergraduate medical training, which span all four years of medical school training and employ teaching technologies which emphasize student involvement through he use of problem-based small groups, computer interactive, casebased learning, and direct clinical experience; 3) use of our extensive outreach programs in sleep medicine and psychiatry to provide educational interventions for mental health workers and primary care physicians; 4) Development of educational material which are exportable and applicable in medical schools and other learning institutions throughout the country; 5) Dissemination of developed resources to institutions nationally by traditional publishing avenues and electronic means; 6) Evaluation of educational impact by systematic testing of both knowledge and attitude change which occur in response to educational interventions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: OUTCOMES OF SLEEP DISORDERS IN OLDER MEN Principal Investigator & Institution: Barrett-Connor, Elizabeth L.; Professor and Chair; Family and Preventive Medicine; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 92093 Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 30-JUN-2007 Summary: (provided by applicant): It is estimated that over 50% of adults aged 65 and older report some sleep disruption, while about 20% suffer from chronic insomnia. Obstructive sleep apnea, a major cause of daytime drowsiness, occurs in an estimated 20-60% of older people, depending on the definition used and the specific population
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being studied. Despite the high prevalence of sleep disorders in the elderly, there have been relatively few studies focused on the consequences. Most studies have been limited by cross-sectional design, small sample size, or lack of comprehensive and objective assessment of sleep. The proposed study, Outcomes of Sleep Disorders in Older Men, will take advantage of the established cohort that has been recruited for the Osteoporotic Fractures in Men (MrOS) study (5U01AR045647-Dr. Eric Orwoll, PI). MrOS, a 7-year study that began in July 1999, is a multi-center prospective study of approximately 6000 men aged 65 and older. During the MrOS baseline visit, a broad variety of measurements were collected, including body composition and body fat distribution (by DEXA and quantitative computed tomography), bone density, anthropometry, performance-based tests of strength and balance, medical history, medication use, smoking and alcohol use, and other parameters. Blood, urine, and DNA specimens have been archived for use in future studies of importance to the health of older men. In a subcohort of 3000 MrOS participants, we propose to add comprehensive and accurate assessments of sleep using in-home polysomnography, wrist actigraphy, questionnaires and other measures; and prospective adjudication of CVD events, to the extensive measures that have already been performed or planned in the MrOS cohort study. These new measures will enable us to test several important hypotheses: 1) to characterize the associations between sleep disruption and subsequent CVD events during 3.5 years of follow-up, 2) to determine if sleep disturbances are associated with an increased risk of total and cause-specific mortality in older men, 3) to test whether sleep disturbances are associated with increased risk of falls and decreased physical function, 4) to test whether sleep disturbances are associated with impaired cognitive function in older men, and 5) to test whether sleep disorders are associated with bone density and fracture risk in older men. We will also supplement the bank of MrOS specimens to allow for testing of future hypotheses concerning the role of sleep in the development of age-related diseases and conditions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: OUTCOMES BIRMINGHAM
OF
SLEEP
DISORDERS
IN
OLDER
MEN-
Principal Investigator & Institution: Lewis, Cora E.; Medicine; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 30-JUN-2007 Summary: (provided by applicant): It is estimated that over 50% of adults aged 65 and older report some sleep disruption, while about 20% suffer from chronic insomnia. Obstructive sleep apnea, a major cause of daytime drowsiness, occurs in an estimated 20-60% of older people, depending on the definition used and the specific population being studied. Despite the high prevalence of sleep disorders in the elderly, there have been relatively few studies focused on the consequences. Most studies have been limited by cross-sectional design, small sample size, or lack of comprehensive and objective assessment of sleep. The proposed study, Outcomes of Sleep Disorders in Older Men, will take advantage of the established cohort that has been recruited for the Osteoporotic Fractures in Men (MrOS) study (5U01AR045647-Dr. Eric Orwoll, PI). MrOS, a 7-year study that began in July 1999, is a multi-center prospective study of approximately 6000 men aged 65 and older. During the MrOS baseline visit, a broad variety of measurements were collected, including body composition and body fat distribution (by DEXA and quantitative computed tomography), bone density, anthropometry, performance-based tests of strength and balance, medical history, medication use, smoking and alcohol use, and other parameters. Blood, urine, and DNA
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specimens have been archived for use in future studies of importance to the health of older men. In a subcohort of 3000 MrOS participants, we propose to add comprehensive and accurate assessments of sleep using in-home polysomnography, wrist actigraphy, questionnaires and other measures; and prospective adjudication of CVD events, to the extensive measures that have already been performed or planned in the MrOS cohort study. These new measures will enable us to test several important hypotheses: 1) to characterize the associations between sleep disruption and subsequent CVD events during 3.5 years of follow-up, 2) to determine if sleep disturbances are associated with an increased risk of total and cause-specific mortality in older men, 3) to test whether sleep disturbances are associated with increased risk of falls and decreased physical function, 4) to test whether sleep disturbances are associated with impaired cognitive function in older men, and 5) to test whether sleep disorders are associated with bone density and fracture risk in older men. We will also supplement the bank of MrOS specimens to allow for testing of future hypotheses concerning the role of sleep in the development of age-related diseases and conditions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: OUTCOMES OF SLEEP DISORDERS IN OLDER MEN-PALO ALTO Principal Investigator & Institution: Stefanick, Marcia L.; Associate Professor of Medicine; Medicine; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 30-JUN-2007 Summary: (provided by applicant): It is estimated that over 50% of adults aged 65 and older report some sleep disruption, while about 20% suffer from chronic insomnia. Obstructive sleep apnea, a major cause of daytime drowsiness, occurs in an estimated 20-60% of older people, depending on the definition used and the specific population being studied. Despite the high prevalence of sleep disorders in the elderly, there have been relatively few studies focused on the consequences. Most studies have been limited by cross-sectional design, small sample size, or lack of comprehensive and objective assessment of sleep. The proposed study, Outcomes of Sleep Disorders in Older Men, will take advantage of the established cohort that has been recruited for the Osteoporotic Fractures in Men (MrOS) study (5U01AR045647-Dr. Eric Orwoll, PI). MrOS, a 7-year study that began in July 1999, is a multi-center prospective study of approximately 6000 men aged 65 and older. During the MrOS baseline visit, a broad variety of measurements were collected, including body composition and body fat distribution (by DEXA and quantitative computed tomography), bone density, anthropometry, performance-based tests of strength and balance, medical history, medication use, smoking and alcohol use, and other parameters. Blood, urine, and DNA specimens have been archived for use in future studies of importance to the health of older men. In a subcohort of 3000 MrOS participants, we propose to add comprehensive and accurate assessments of sleep using in-home polysomnography, wrist actigraphy, questionnaires and other measures; and prospective adjudication of CVD events, to the extensive measures that have already been performed or planned in the MrOS cohort study. These new measures will enable us to test several important hypotheses: 1) to characterize the associations between sleep disruption and subsequent CVD events during 3.5 years of follow-up, 2) to determine if sleep disturbances are associated with an increased risk of total and cause-specific mortality in older men, 3) to test whether sleep disturbances are associated with increased risk of falls and decreased physical function, 4) to test whether sleep disturbances are associated with impaired cognitive function in older men, and 5) to test whether sleep disorders are associated with bone density and fracture risk in older men. We will also supplement the bank of MrOS
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Insomnia
specimens to allow for testing of future hypotheses concerning the role of sleep in the development of age-related diseases and conditions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: OUTCOMES OF SLEEP DISORDERS IN OLDER MEN-PORTLAND Principal Investigator & Institution: Orwoll, Eric S.; Professor of Medicine; Endodontology; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 30-JUN-2007 Summary: (provided by applicant): It is estimated that over 50% of adults aged 65 and older report some sleep disruption, while about 20% suffer from chronic insomnia. Obstructive sleep apnea, a major cause of daytime drowsiness, occurs in an estimated 20-60% of older people, depending on the definition used and the specific population being studied. Despite the high prevalence of sleep disorders in the elderly, there have been relatively few studies focused on the consequences. Most studies have been limited by cross-sectional design, small sample size, or lack of comprehensive and objective assessment of sleep. The proposed study, Outcomes of Sleep Disorders in Older Men, will take advantage of the established cohort that has been recruited for the Osteoporotic Fractures in Men (MrOS) study (5U01AR045647-Dr. Eric Orwoll, PI). MrOS, a 7-year study that began in July 1999, is a multi-center prospective study of approximately 6000 men aged 65 and older. During the MrOS baseline visit, a broad variety of measurements were collected, including body composition and body fat distribution (by DEXA and quantitative computed tomography), bone density, anthropometry, performance-based tests of strength and balance, medical history, medication use, smoking and alcohol use, and other parameters. Blood, urine, and DNA specimens have been archived for use in future studies of importance to the health of older men. In a subcohort of 3000 MrOS participants, we propose to add comprehensive and accurate assessments of sleep using in-home polysomnography, wrist actigraphy, questionnaires and other measures; and prospective adjudication of CVD events, to the extensive measures that have already been performed or planned in the MrOS cohort study. These new measures will enable us to test several important hypotheses: 1) to characterize the associations between sleep disruption and subsequent CVD events during 3.5 years of follow-up, 2) to determine if sleep disturbances are associated with an increased risk of total and cause-specific mortality in older men, 3) to test whether sleep disturbances are associated with increased risk of falls and decreased physical function, 4) to test whether sleep disturbances are associated with impaired cognitive function in older men, and 5) to test whether sleep disorders are associated with bone density and fracture risk in older men. We will also supplement the bank of MrOS specimens to allow for testing of future hypotheses concerning the role of sleep in the development of age-related diseases and conditions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: PHARMACOTHERAPY OF ALCOHOLISM AND COMORBID INSOMNIA Principal Investigator & Institution: Brower, Kirk J.; Associate Professor of Psychiatry; Psychiatry; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2001; Project Start 27-SEP-1999; Project End 31-AUG-2004 Summary: Kirk J. Brower, M.D., an associate professor of psychiatry with tenure at the University of Michigan (UM) Medical School, is applying for the Midcareer Investigator
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Award in Patient-Oriented Research. The UM Department of Psychiatry provides a rich environment for alcohol research, including a large base of NIH funding and an established Alcohol Research Center that is currently engaged in multiple clinical studies. Dr. Brower, broad-certified in addiction psychiatry, is Executive Director of Chelsea Arbor Treatment Center, the dedicated facility in the Department that exclusively treats people with alcohol and other drug problems. He is also the director of the ACGME-accredited fellowship program in addiction psychiatry at UM and coprincipal investigator on the Department s NIAAA T32 Training Grant for postdoctoral research fellows. He mentors this year s competitively selected (one per year) ACNP Glaxo Wellcome Research Fellow in Clinical Neuropharmacology. Dr. Brower s longterm career goals are to develop and disseminate new therapeutic options for patients with alcoholism and alcohol abuse who are likely to relapse despite current or conventional treatments. Comorbid insomnia, craving, and mood disturbances are targeted because they may increase relapse risk via neurobiological mechanisms that are amenable to pharmacotherapy. Dr. Brower s short-term career goals are to increase his expertise in sleep medicine, sleep research, and pharmacotherapy trials. His career development plan includes advanced coursework in clinical research design and biostatistics, focused activity in sleep medicine at the University of Michigan, and special leave to visit other institutions where exemplary sleep research and/or state-ofthe-art pharmacotherapy trials for alcoholism are being conducted. Dr. Brower has current research funding from Pfizer, Inc. to study the effects of sertraline on the sleep of depressed alcoholics. The proposed research project is a randomized, double-blind, placebo-controlled trial gabapentin for treating alcoholism and comorbid insomnia. This 6-week trial with an additional 6-week follow-up period will investigate the effects of medication on both sleep and drinking outcomes, and it will utilize polysomnographic measures as potential neurophysiological predictors of treatment outcome. Given the high prevalence, costs and comorbidity of alcoholism and insomnia, this topic requires considerably more research attention than it has received. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PHENOTYPICAL EXPRESSION OF ANXIETY AND SLEEP Principal Investigator & Institution: Sanford, Larry D.; Associate Professor; Pathology and Anatomy; Eastern Virginia Medical School Norfolk, Va 23507 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-MAY-2003 Summary: (adapted from the applicants' abstract) The long-term goal of this project is to further the understanding of how emotional factors influence sleep. Emotional state has a strong influence on sleep quality and amount. This statement can be attested to by almost everyone, and it is factually supported by the observed role of emotional factors in human sleep medicine, particularly sleep disorders related to a psychiatric condition. However, the role of emotion has virtually been ignored in basic sleep research, possibly because of the lack of a clear anatomical focus, or perhaps because of a lack of established models. It is now becoming increasingly apparent that the amygdala, the limbic center of emotion, has a strong modulatory role in the control of sleep. Inbred mouse strains are being examined in order to find models of anxiety and mood disorders. The investigators plan to study sleep in inbred mouse strains with differences in emotional reactivity in order to begin to understand how genetics and the environment interact in producing the effects of emotion on sleep. The investigators' strategy is to : 1) establish protocols for studying how emotion affects sleep in inbred mouse strains, 2) identify the anatomical regions that could account for strain differences in emotional reactivity as it affects sleep, and 3) determine the functional
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significance of these regions in the control of emotion and sleep. To accomplish these goals, the investigators will examine the effect of fear conditioning on sleep, identify the activated brain areas that affect sleep and examine the function of these regions by selectively preventing their activation in response to fear conditioning. These studies will help elucidate into how stress, emotion and environmental factors influence sleep. This work will advance the understanding of how stress and anxiety affect sleep and may give insight into sleep disorders such as insomnia and into mental disorders in which sleep is affected. The investigators findings may be especially relevant to posttraumatic stress disorder (PTSD), which is typically characterized by a prominent sleep disturbance in the aftermath of exposure to a psychologically traumatic stressor. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PSYCHONEUROIMMUNOLOGICAL CORRELATES OF SLEEP IN HIV Principal Investigator & Institution: Phillips, Kenneth D.; Professor; None; University of South Carolina at Columbia Byrnes Bldg., Room 501 Columbia, Sc 29208 Timing: Fiscal Year 2001; Project Start 01-AUG-2000; Project End 31-JUL-2003 Summary: Insomnia, a disruption of sleep quality, is a frequent symptom of HIV disease that is characterized by numerous changes in nervous, endocrine, and immune functions. Initiation and maintenance of sleep depends on complex interactions of these three systems. Frequently, insomnia appears before the diagnosis of HIV infection and persists throughout the course of the disease. The few studies that have looked at sleep disturbances in relation to a rising viral load or a declining CD4+ count have not taken into account the relationship among sleep quality and three markers of immune activation (HIV viral load, beta-2-macroglobulin, and Epstein-Barr virus). Therefore, the specific aim of this feasibility study is to describe the relationships among stress, immune activation, psychological, endocrine, and immune correlates of sleep, and sleep quality in Persons with HIV (PWHIV) within the context of psychoneuroimmunology (PNI) theory. A cross-sectional, correlational design will be employed in which HIVpositive men (n=100), ages 18-40, who experience insomnia will be asked to participate. The subjects will complete a battery of instruments that include the: Perceived Stress Scale, and Profile of Mood States. Blood and urine samples will be collected for two immune activation markers (beta-2- microglobulin and Epstein-Barr Virus-Viral Capsid Antigen), endocrine correlates of sleep (ACTH, cortisol, epinephrine, and norepinephrine), and immune correlates of sleep (natural killer cell activity, IL-1, lL-6, and TNFalpha). Sleep quality, will be measured with the Wrist Actigraph as well as polysomnography for a selected group. The long-term goal of this research career award is to develop expertise in sleep and psychoimmunology research in order to develop and test behavioral, cognitive, and complementary therapy interventions to improve sleep quality and immunity in PWHIV and other chronic illnesses. Dr. David Dinges, an expert in sleep research, and Dr. Michael Antoni, an expert in PNI and AIDS, will provide the mentorship needed to build a research program in sleep and PNI in PWHIV. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: TREATMENTS
REDUCING
JET-LAG
WITH
PRACTICAL
CIRCADIAN
Principal Investigator & Institution: Eastman, Charmane I.; Professor of Psychology; Rush-Presbyterian-St Lukes Medical Ctr Chicago, Il 60612
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Timing: Fiscal Year 2001; Project Start 01-SEP-2000; Project End 31-MAY-2005 Summary: Jet-lag is one of society's most prevalent disorders. Symptoms include insomnia, daytime sleepiness, fatigue, decrements in alertness and performance, dysphoric mood, loss of concentration, disorientation, and gastrointestinal distress. Jetlag is not just the bane of tourists; it can impair the judgment and performance of businessmen and women, diplomats and the military. The symptoms of jet-lag occur because the internal circadian clock is slow to re-entrain to the sleep/wake schedule required in the new time zone. When several time zones are crossed, travelers are forced to sleep at the "wrong" phase of their circadian cycle, when they are physiologically set for waking, and then try to stay awake when they are physiologically set to sleep. As the circadian clock gradually phase shifts to re-entrain, the symptoms of jet-lag gradually dissipate. It takes longer to adapt after an eastward that after a westward flight, because the circadian clock is slower to advance than to delay. Furthermore, after an eastward flight, circadian rhythms may re-entrain in the wrong direction, e.g., they may delay 16 hrs instead of advancing 8 hrs, further prolonging the symptoms of jet-lag. The investigators propose to test treatments to phase advance the circadian clock before an eastward flight, in order to prevent or reduce the symptoms of jet-lag. The treatments will include 3 days of a gradually advancing sleep schedule, bright artificial light after waking, and afternoon melatonin pills. These treatments are specifically designed to be feasible for real travelers to use at home before a flight. The outcome measures will be the magnitude of phase advance on the day that corresponds to the day of flight, measured from the circadian rhythm of endogenous melatonin secretion. They will also measure the side effects of treatment, the "price" that travelers would have to pay in order to prevent or reduce jet-lag, including sleep loss (from wrist activity monitors and sleep logs) and daytime sleepiness and fatigue (from questionnaires). The goal is to develop practical recommendations for real travelers. 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
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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 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: RESPONSIVENESS OF THE AGING CIRCADIAN CLOCK TO LIGHT Principal Investigator & Institution: Benloucif, Susan J.; Mol Pharm & Biol Chemistry; Northwestern University Office of Sponsored Programs Chicago, Il 60611 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-JUL-2005 Summary: (adapted from investigator's abstract): The investigator's long-term goal is to understand the basis of and develop effective therapies for chronic sleep disturbances in older adults. One common sleep disorder in older adults is advanced sleep phase, accompanied by sleep maintenance insomnia and early morning awakenings. This can shorten the total sleep time and lead to daytime fatigue and impaired performance. The advance in sleep is associated with an advances in the timing of the circadian core body temperature rhythm which suggests an advance in the timing of the circadian clock. The cause of this advance is unknown. Preliminary date from the investigators laboratory suggests that elderly subjects do not phase delay following exposure to 4000 lux for 3 hours before the temperature minimum, a time that usually does delay the rhythm in younger adults. The first goal of this application is to understand the mechanism underlying the age-related change in responsiveness of the clock to light. The second goal is to assess whether it is possible to compensate for age-related change in the responsiveness of the aging circadian clock to light by either increasing the intensity of the light exposure or by pharmacological treatment with the calcium channel antagonist nimodipine. The proposed experiments will provide a vast amount of data in which to better understand the effect of age on circadian rhythms and sleep and lead to improved treatments for circadian rhythm and sleep disorders in older adults. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SEX HORMONES SLEEP AND CIRCADIAN RHYTHMICITY IN AGING Principal Investigator & Institution: Murphy, Patricia J.; Associate Research Scientist; Psychiatry; Weill Medical College of Cornell Univ New York, Ny 10021 Timing: Fiscal Year 2001; Project Start 01-SEP-1998; Project End 31-MAR-2003
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Summary: Changes in the processes controlling sleep that accompany aging result in widespread complaints of sleep disturbance in otherwise healthy older individuals. It is likely that age-related changes in many physiological systems interact to produce these sleep problems. One such system is the hypothalamic-pituitary-gonadal (HPG) axis. Gonadal steroids exhibit significant declines with age, resulting in altered negative feedback to the hypothalamus, and unregulated production of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Recent evidence demonstrates that these alterations continue and worsen with increasing age. That changing levels of gonadal hormones affect sleep quality in aging is supported by both anecdotal and empirical evidence. For example, up to two-thirds of perimenopausal women complain of sleep problems. Further, higher LH levels are associated with awakenings from sleep, and hormone replacement therapy improves objectively-measured sleep. Although investigations of sex hormones and sleep in men are rare, lower levels of testosterone in aging men have been associated with poorer sleep quality. Indeed, the few studies that have assessed sleep complaints in the context of age-associated changes in HPG functioning strongly suggest that further investigation is needed. In addition, while changes in the circadian timing system are widely believed to contribute to sleep problems in older individuals, little is known about whether circadian patterns of sex hormone release are modified as a function of aging. The proposed research plan combines a chronobiological approach to the study of changes in the HPG axis in aging with an investigation of whether sex hormone levels are associated with age-related sleep problems. One study will assess whether there are circadian rhythms in sex hormones independent of sleep, and whether patterns of gonadal hormone release are altered with aging. The second study will examine whether the balance of sex steroids and gonadotropins differs between older individuals without sleep complaints and those with sleep maintenance insomnia. The combination of findings from these studies will clarify our understanding of how sex hormones, sleep, and circadian rhythmicity interact in aging, providing an avenue for investigating hormone replacement therapies as treatments for sleep problems in older individuals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SLEEP AND CHRONOBIOLOGY OF LATE-LIFE DEPRESSION Principal Investigator & Institution: Szuba, Martin P.; Assistant Professor; Psychiatry; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 15-SEP-1998; Project End 30-JUN-2002 Summary: This application proposes Martin P. Szuba, M.D. for a Mentored Clinical Scientist Development Award at the University of Pennsylvania. The aims of this program include: 1) to support his development into an independent research scientist 2) to support and enhance the applicant's development as an investigator in sleep and chronobiology in the elderly; 3) to develop him for a faculty leadership role in mood disorders at Penn; and 4) to enhance the study of late-life mood disorders at Penn, using a chronobiologic approach. These aims will be structured around a four-part plan: 1) A program of formal academic courses and tutorials aimed at enhancing his research skills. 2) Research training, supervised by Drs. David Dinges and Ira Katz. This training will include supervised participation in three ongoing studies of the Center for Sleep and Respiratory Neurobiology and the Clinical Research Center (CRC) in Depression in the Aged: Medical- Psychiatric Co-Morbidity (I. Katz, PI). 3) Performance of a separate research project: The first systematic randomized, double-blind, placebo-controlled treatment trial of the effects of exogenous melatonin administration on sleep, mood, and circadian rhythms in depressed elderly subjects. The specific aims of the study include a
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thorough evaluation in elderly depressed subjects with insomnia of subjective, behavioral, and physiological indices of sleep, in the laboratory and at home, as well as recording of circadian physiology during an unmasking protocol (constant routine), prior to and following treatment with melatonin or placebo. 4)Preparation, as Principal Investigator, of an independent research grant application. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SLEEP AND CIRCADIAN RHYTHMS AFTER PINEAL RESECTION Principal Investigator & Institution: Macchi, Mariana M.; New York State Psychiatric Institute 1051 Riverside Dr New York, Ny 10032 Timing: Fiscal Year 2003; Project Start 01-DEC-2002; Project End 30-NOV-2004 Summary: The hormone melatonin, produced by the pineal gland, is thought to be involved in the regulation of human sleep, body temperature and circadian rhythms, but its mechanisms of action in these areas have not been fully clarified, while its clinical significance remains controversial. The proposed research will examine these issues from a novel perspective, by systematically assessing sleep parameters, core body temperature, cortisol secretion and residual melatonin levels in individuals who have undergone pineal resection. In addition to 24 days of rest-activity recordings through an actigraphy device, the study will consist of two sets of consecutive overnight sessions for the assessment of polysomnographic (PSG) sleep parameters and circadian rhythm parameters of core body temperature, plasma cortisol and melatonin, the latter as a measure of residual pineal functionality. A healthy sex- and age-matched control group will undergo the same procedures. The specific aims of this preliminary study are: (1) to characterize PSG sleep patterns and microstructure in subjects with impaired melatonin production relative to healthy controls; (2) to elucidate the relationship between sleep, melatonin and body temperature in the absence of normal pineal functionality; specifically, we propose to assess (a) whether very low or absent levels of melatonin are accompanied by a dampening of core body temperature rhythm; b) whether insomnia following pineal resection is accompanied by changes in cortisol secretion; (3) to assess the feasibility of the experimental protocol and to obtain data for calculating statistical power of key comparisons, with the future aim of performing larger scale, hypothesisdriven research. 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
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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 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 DISTURBANCES AND RISK FOR ALCOHOL DISORDERS Principal Investigator & Institution: Crum, Rosa M.; Associate Professor; Epidemiology; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001; Project Start 29-SEP-2001; Project End 31-AUG-2003 Summary: (Provided by applicant): The overall aim of this application is to extend and strengthen prior work which has examined the relationship of insomnia and other sleep disturbances with the development of alcohol use disorders and problem drinking. The focus of the proposed analyses is the assessment of these association using data from two existing longitudinal surveys: 1) the Johns Hopkins Precursors study, and 2) the Baltimore ECA Follow-up Study. The primary goal of the current application is to assess the following specific aims: 1) to test whether insomnia and other sleep disturbances are associated with an increased risk for problematic alcohol use, and alcohol abuse and dependence; and whether this relationship differs by sex; 2) to test whether psychiatric comorbidity (such as depressive symptoms , depressive disorders, anxiety, and psychiatric distress) are mediators of this relationship; 3) to assess whether those with remitted alcohol abuse or dependence have higher rates of sleep disturbance compared to those who never abused alcohol; and 4) to assess the natural history of individuals with alcohol abuse and dependence who self-report insomnia and other sleep disturbances, specifically to test whether the prognosis for remission, drinking patterns presence of comorbid psychopathology, and subsequent sleep patterns differ for individuals with an alcohol use disorder, or problem drinking, if they have insomnia at baseline relative to those with alcohol abuse and dependence, or problem drinking who have no sleep disturbance. Prospective analyses of the relationship of insomnia with alcohol use disorders or problematic drinking have been few and of these prior studies, the follow-up intervals have been relatively short. We propose to complete secondary analyses of two well-studied prospective data sets, that have long follow-up intervals (mean of 13 years for the Baltimore ECA Follow- up study, and 36 to 50 years for the Johns Hopkins Precursors Study), and relatively low study attrition, which if
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successfully completed can improve our understanding of insomnia and other sleep difficulties as potential long term risk factors for problematic drinking behavior and alcohol abuse or dependence. Information from these unique data sets allow the ability to assess important mediating, as well as potential confounding and effect modifying characteristics such as the occurrence of depressive symptoms as well as other psychopathology and substance use. The data analyses should provide, in a costeffective manner, information on the relationship of insomnia and alcohol condition, which will help guide future experimental and observational studies. The results may highlight a potential focus for future investigations of prevention and early intervention efforts for reducing the incidence and prevalence of alcohol abuse and dependence. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SLEEP DURING THE PERI-MENOPAUSE IN A MULTI-ETHNIC COHORT Principal Investigator & Institution: Gold, Ellen B.; Director; Epidemiology and Prev Medicine; University of California Davis Sponsored Programs, 118 Everson Hall Davis, Ca 95616 Timing: Fiscal Year 2002; Project Start 15-JUN-2002; Project End 30-SEP-2005 Summary: (provided by applicant) This interactive Research Project Grant (IRPG) will characterize the relationship between menopausal characteristics and sleep in a sample of 430 women: 200 Caucasian, 150 African-American, and 80 Chinese. Although sleep disruptions, insomnia and the incidence of sleep disordered breathing increase in midlife women, little is known about the relationship between menopause and sleep. The impact of vasomotor symptoms and hormone replacement therapy on sleep suggests that the sleep-menopause relationship is not merely a function of age. A greater understanding of the causes of sleep disturbances in mid-life women is important, given the impact of sleep on mental and physical health. Sleep disturbances are associated with a host of negative health outcomes including losses in productivity and quality of life, psychiatric morbidity, immunosuppression, and increased vulnerability to illness and disease. The study aims of this IRPG are to: 1) characterize sleep disturbances in a large, multi-ethnic sample of mid-life women; 2) characterize relationships among menopausal characteristics and sleep disturbances; 3) evaluate the influence of relevant psychobiological factors on the sleep-menopause relationship; and 4) establish baseline data for a future longitudinal study. Four of seven study sites from the ongoing Study of Women s Health Across the Nation (SWAN) will collaborate to recruit a sample of preand peri-menopausal women from the SWAN cohort. Once enrolled in the Sleep Study, participants will begin the protocol at the start of a new menstrual cycle. Ambulatory polysomnography will be conducted in participants homes during days 1-3 of the protocol. Sleep diary, actigraphy, and event monitor recordings of vasomotor symptom data will be collected throughout the cycle. Data will also include five years of Core SWAN study data on menopausal characteristics (bleeding patterns, vasomotor symptoms, hormone levels) and related psychobiological factors. Regression techniques will be used to model relationships among menopausal characteristics, sleep, and related psychobiological factors. The Pittsburgh site will train study personnel in the use of sleep monitoring equipment and will be responsible for processing, scoring, and archiving all sleep data. All sleep study data, as well as relevant data from the Core SWAN study, will be merged and analyzed by the Michigan site. The Chicago and UC Davis PIs will co-chair the Sleep Study Steering Committee. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SLEEP DURING THE PERIMENOPAUSE IN A MULTI-ETHNIC COHORT Principal Investigator & Institution: Kravitz, Howard M.; Rush-Presbyterian-St Lukes Medical Ctr Chicago, Il 60612 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2006 Summary: This interactive Research Project Grant (IRPG) will characterize the relationship between menopausal characteristics and sleep in a sample of 430 women: 200 Caucasian, 150 African- American, and 80 Chinese. Although sleep disruptions, insomnia and the incidence of sleep disordered breathing increase in mid- life women, little is known about the relationship between menopause and sleep. The impact of vasomotor symptoms and hormone replacement therapy on sleep suggests that the sleep- menopause relationship is not merely a function of age. A greater understanding of the causes of sleep disturbances in mid- life women is important, given the impact of sleep on mental and physical health. Sleep disturbances are associated with a host of negative health outcomes including losses in productivity and quality of life, psychiatric morbidity, immunosuppression, and increased vulnerability to illness and disease. The study aims of this IRPG are to: 1) characterize sleep disturbances in a large, multi-ethnic sample of mid-life women; 2) characterize relationships among menopausal characteristics and sleep disturbances; 3) evaluate the influence of relevant psychobiological factors on the sleep-menopause relationship; and 4) establish baseline data for a future longitudinal study. Four of seven study sites from the ongoing Study of Women's Health Across the Nation (SWAN) will collaborate to recruit a sample of preand peri-menopausal women from the SWAN cohort. Once enrolled in the Sleep Study, participants will begin the protocol at the start of a new menstrual cycle. Ambulatory polysomnography will be conducted in participants' homes during days 1-3 of the protocol. Sleep diary, actigraphy, and event monitor recordings of vasomotor symptom data will be collected throughout the cycle. Data will also include five years of Core SWAN study data on menopausal characteristics (bleeding patterns, vasomotor symptoms, hormone levels) and related psychobiological factors. Regression techniques will be used to model relationships among menopausal characteristics, sleep, and related psychobiological factors. The Pittsburgh site will train study personnel in the use of sleep monitoring equipment and will be responsible for processing, scoring, and archiving all sleep data. All sleep study data, as well as relevant data from the Core SWAN study, will be merged and analyzed by the Michigan site. The Chicago and UC David PIs will co-chair the Sleep Study Steering Committee. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SLEEP IN OLDER WOMEN--EFFECTS OF ESTROGEN Principal Investigator & Institution: Moe, Karen E.; Psychiatry and Behavioral Scis; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2001; Project Start 01-MAY-1998; Project End 31-OCT-2003 Summary: (adapted from investigator's abstract): Sleep complaints increase significantly with age in both men and women, but the increase is especially striking in women. Older women experience more nighttime awakenings, longer sleep onset latencies, and "lighter" sleep. Insomnia, disrupted sleep, and consequent daytime drowsiness are associated with an increased risk of accidents, increased utilization of health care and sedative-hypnotic medications, and a reduced quality of life. Older women receive a disproportionate number of prescriptions for sedative-hypnotics, which can exacerbate sleep apnea and lead to daytime carryover effects such as sedation, falls and subsequent
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fractures, and cognitive impairment. A better understanding of the sleep changes experienced by older women is sorely needed. One contributing factor may be agerelated changes in sex steroids such as estrogen. The very low levels of estrogen that occur post-menopause have wide-ranging chronic effects, from increased cardiovascular risk factors to possible effects on memory. Sleep changes in older women may also be related to this dramatic change in hormonal milieu. Several studies have shown that ERT can improve the sleep of peri-menopausal women, and our preliminary data shows that the use of ERT is associated with better sleep in older post-menopausal women. Estrogen acts on several brain areas important for sleep and circadian rhythms (e.g., the suprachiasmatic nucleus, the hypothalamic pre-optic area, and the pineal gland). Previous studies of ERT effects on sleep were based on peri-menopausal women who were experiencing hot flashes and/or other menopausal symptoms including depression. All but a few of these studies were based on brief subjective sleep ratings. No published studies have examined the effect of ERT on the sleep of post-menopausal women., i.e., women who are several years past menopause, menopausal symptoms, and menopause-related hormone fluctuations. The proposed study will employ laboratory-based polysomnography and a randomized, placebo-controlled withinsubjects design to assess the effect of six months ERT or placebo on the sleep and circadian rhythms of post-menopausal women. The results will help determine the role of age-related estrogen decline in the decreased sleep quality of older women. This study is the first step in a research program investigating the relationship between sex steroids and sleep in older individuals. 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 2001; Project Start 30-SEP-1999; Project End 31-JUL-2003 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 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
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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: STUDY OF OSTEOPOROTIC FRACTURES Principal Investigator & Institution: Cauley, Jane A.; Professor; Epidemiology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2001; Project Start 01-FEB-1986; Project End 31-JUL-2006 Summary: (provided by applicant): The Study of Osteoporotic Fractures (SOF) is a multi-center longitudinal study in a cohort of 9,704 older women. SOF has comprehensive data about risk factors for osteoporosis and other diseases, along with an archive of serum, buffy coat and urine specimens. Data from SOF have served for: (1) developing osteoporosis guidelines, (2) estimating the cost-effectiveness of screening for osteoporosis, and (3) planning trials of osteoporosis therapies. They propose to renew SOF to sustain this unique resource and to pursue several new hypotheses. Osteoporosis is a chronic disease and prevention of fractures must be considered over the very longterm, not just the 3-5 year duration of most studies in the field. As the study of osteoporosis and aging with the longest (nearly 15 years) follow-up, SOF will provide the foundation for describing ways to identify people at greatest risk of osteoporosis and fractures decades in advance. They envision a new generation of clinical guidelines based on long-term prediction of risk of fractures and disability. Because they have enriched the cohort with African-American women, SOF will also provide unique information on risk factors for osteoporosis and non-spine fractures in older African American women. SOF was the first study to show a link between low BMD and risk of stroke and this has helped to fuel the interest and new investigations about the links between arterial calcification and osteoporosis. If they demonstrate, and can begin to explain, the link between these two diseases, this may lead to screening tools and treatments that simultaneously decrease the risk of both of these disabling conditions. Preliminary results from SOF suggest that impaired sleep may be a major cause of fractures, disability and decline in cognition in older women. If the next phase of SOF confirms these relationships using more objective measures of insomnia and other sleep disorders, then this might change current clinical policies and practices toward more aggressive screening and better coverage for treatment of sleep disorders. Finally, the value of SOF could be magnified by recruiting other scientists to work on SOF data and samples. They propose to make the database easily accessible to investigators outside of SOF and assist them in making productive use of a database that represents one of the most comprehensive prospective sources of information about the health of older women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: TRANSCRIPTIONAL REGULATION OF PDF IN DROSOPHILA Principal Investigator & Institution: Park, Jae H.; Professor; Biochemistry, Cellular and Molecular Biology; University of Tennessee Knoxville Knoxville, Tn 37996 Timing: Fiscal Year 2002; Project Start 02-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant): Daily rhythms of physiology and behavior in most life forms are driven by internal circadian pacemakers which use the physically fluctuating stimuli to measure the passage of time. Disruptions of biological clock cause severe health problems in our society, including jet-lag, insomnia, and shiftwork-related illnesses. Similarities in molecular mechanisms underlying central pace-making functions in mammals and fruit flies (Drosophila melanogaster) suggest that Drosophila is an excellent model system to study the biological clock. However, the mechanisms by which the central oscillators regulate the overt physiological and behavioral rhythms (output pathways) are largely unknown. Our recent studies identified the first circadian messenger; it is a neuropeptide, pigment-dispersing factor (PDF). Interestingly, the coreclock transcription factors activate pdf expression in the pacemaker cells. These studies indicate that any factors affecting normal PDF production can cause aberrant rhythms. Given the importance of the PDF in the regulation of clock output, the objectives of this application are to examine transcriptional regulatory mechanisms of the pdf gene in Drosophila by performing the following specific aims: 1. Dissect pdf promoter. This will be accomplished by site-directed mutagenesis of the pdf enhancer and subsequent functional in vivo assay. Yeast one-hybrid and EMS-mutagenesis screen will be employed to find pdf transcriptional regulators. 2. Characterize a new rhythm mutant. The gene disrupted by a P-element insertion will be isolated and characterized molecularly. 3. Clone the pdf gene in D. virilis (Dv-pdf). Using RT-PCR or library screening, we will isolate the Dv-pdf gene and its regulatory elements. The Dv-pdf promoter will be assayed heterologously in D. melanogaster. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: TRAZODONE FOR SLEEP DISTURBANCE--EARLY ALCOHOL RECOVERY Principal Investigator & Institution: Friedmann, Peter D.; Associate Professor; Rhode Island Hospital (Providence, Ri) Providence, Ri 02903 Timing: Fiscal Year 2001; Project Start 27-SEP-2001; Project End 31-JUL-2005 Summary: Patients in early recovery from alcohol dependence commonly experience poor sleep, but evidence supporting pharmacological treatment of their sleep disturbance is lacking. Trazodone, an F.D.A.-approved sedating antidepressant, is one of the most commonly prescribed medications for insomnia nationwide and the most commonly prescribed medication for sleep disturbance after alcohol detoxification. Because poor sleep is a "high risk situation," can lead to drinking to relieve insomnia, is associated with negative affective states, and might impair the ability to cope with urges to drink, this proposal's aims are: 1. To determine whether bedtime treatment with lowdose trazodone reduces recurrent drinking among sleep-disturbed alcohol dependent subjects in early recovery. Process analyses will examine whether trazodone has greater efficacy in subjects with certain attributes, such as worse global sleep quality, fatigue or depressive symptoms, and whether changes in these attributes mediate trazodone's effect on recurrent drinking. 2. To explore whether trazodone is associated with differences in sleep architecture, and whether these differences are associated with improved sleep quality and reductions in recurrent drinking. To accomplish these aims, we propose a randomized, double-blind trial of low-dose trazodone versus identical
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placebo at bedtime for 12-weeks in 266 sleep-disturbed alcohol dependent subjects who will be enrolled 5-7 days after inpatient detoxification. Both groups will receive a booklet on basic sleep hygiene. Urn randomization will ensure balance by depressive symptoms, homelessness, and gender. Subjects will receive follow-up interviews 4-, 12-, and 24-weeks later, with biomarker confirmation of self-reported alcohol consumption. Latent growth analysis will examine whether trazodone increases the subsequent percentage of days abstinent and drinks per drinking day. Our research team is highly experienced in alcohol research, sleep disorders, and clinical trials in substance-abusing populations. Our extensive contacts with community agencies and substance abuse treatment facilities should enhance follow-up rates. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TREATING NEUROPSYCHIATRIC PROBLEMS IN DEMENTIA Principal Investigator & Institution: Mccurry, Susan M.; Psychiatry and Behavioral Scis; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2001; Project Start 01-JUN-1999; Project End 31-MAY-2004 Summary: The objective of this five year academic award is to establish Dr. McCurry as an independent researcher who can integrate expertise in a range of behavioral and somatic interventions, and employ physiological measures to assess the impact of these interventions, in order to improve the sleep, psychosocial functioning, and quality of life of older adults. This award will build on Dr. McCurry's existing skills and training in psychological treatment outcome research, and will provide her with an opportunity to expand her knowledge into the field of sleep and treatment of nighttime behavioral disturbances in patients with dementia. Dr. McCurry completed a two year postdoctoral research fellowship in geriatric psychology. She has authored or co-authored 19 articles and 3 book chapters since that fellowship that are either published or in press. The aim of the present award is to increase her knowledge of: 1) the interaction between age, psychiatric conditions, medical comorbidy, and sleep quality; 2) objective sleep assessment and monitoring techniques that may also generalize to monitoring of other dementia-related behavior problems; and 3) somatic therapies (e.g., light exposure and exercise) that may be appropriate for the treatment of insomnia as well as other mental disorders in older adults. Research has suggested that nighttime behavioral disturbances in persons with Alzheimer's disease (AD) are a common source of patient institutionalization and caregiver psychological and physical burden. This career development award will allow Dr. McCurry to evaluate the short- and long-term feasibility and efficacy of an 8-week combination behavioral and somatic treatment for improving sleep in persons diagnosed with AD. It will enable her to identify patient and caregiver characteristics associated with treatment outcome, such as dementia severity, level of behavioral disturbance, presence of depression or comorbid disease, cultural background, and age. This study will build upon Dr. McCurry's existing major collaborations with faculty at University of Washington in the areas of behavior management (Dr. Linda Teri) and age-related change in sleep (Drs. Michael Vitiello and Pat Prinz). In addition, Dr. McCurry will develop new collaborative relationships with Drs. Sonia Ancoli-Israel and Charles Reynolds to develop an expertise in sleep assessment, 24-hour activity and light monitoring, and the role of comorbid physical, psychiatric, and environmental factors in the development of sleep problems in the elderly. This training mechanism will assist Dr. McCurry in making the transition to an independent investigator at the University of Washington, as well as a teacher and clinician in geriatric psychology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: TREATMENT OF HYPNOTIC DEPENDENCE IN OLDER ADULTS Principal Investigator & Institution: Lichstein, Kenneth L.; Professor; Psychology; University of Memphis Memphis, Tn 38152 Timing: Fiscal Year 2001; Project Start 20-FEB-1999; Project End 31-AUG-2003 Summary: Hypnotic-dependent insomnia (HDI) refers to insomnia maintained by the chronic use of sleep medications (hypnotics) with associated tolerance and dependence. As disproportionately high users of hypnotics, older adults are most likely to develop HDI, and they are most vulnerable to the negative side-effects associated with chronic benzodiazepine use. The efficacy of psychological treatments for insomnia is well established, but there has been relatively little research on the use of these same treatments for people with insomnia who are also dependent on hypnotics. The planned study will treat 90 older adults diagnosed with HDI secondary to benzodiazepine use in a randomized experiment with three conditions: scheduled gradual hypnotic withdrawal supplemented by a placebo desensitization, and scheduled gradual hypnotic withdrawal only. Assessments at baseline, post-treatment/withdrawal, and 1year follow-up will include monitoring of hypnotic consumption, self report and laboratory sleep evaluations, drug screens, and measures of psychological and global functioning. Side-effects during the drug withdrawal period will also be monitored by self-report. The study will attempt to determine if adding psychological treatments to gradual drug withdrawal will improve success of drug withdrawal, diminish withdrawal side-effects, improve sleep, or improve psychological and global functioning compared to gradual drug withdrawal alone in the management of HDI with older adults. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: TREATMENTS FOR INSOMNIA Principal Investigator & Institution: Yesavage, Jerome A.; Professor; Psychiatry and Behavioral Sci; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2001; Project Start 01-APR-1990; Project End 31-JUL-2004 Summary: (adapted from investigator's abstract): The investigator's plan is to evaluate the short-term and longer-term efficacy of three non-pharmacologic treatments for insomnia: (1) a behavioral treatment that uses the principles of sleep hygiene (HYG) in addition to timed exposure to a placebo light, (2) HYG plus timed bright light exposure in the morning (HYG+AM LIGHT), and (3) HYG plus timed bright light exposure in the afternoon (HYG+PM LIGHT). Hypotheses are: (1) Efficacy: bright light therapy will have a significant additive effect when combined with sleep hygiene compared to sleep hygiene alone. Primary outcome measures will be basic sleep parameters as recorded by actigraphy with subsidiary analyses using polysomnography (PSG). It is expected that improvement will be present at the end of the 3-month treatment and over a 3-month follow-up. (2) Individual Differences in Response (Moderators): There will be individual differences in the efficacy of the two HYG+LIGHT groups depending on the phase, amplitude, or the degree of synchronization of circadian rhythm measures demonstrated prior to treatment. It is also expected that genetic markers such as the human CLOCK gene, found to be associated with relative morning versus evening preference, may influence treatment response of insomnia patients receiving bright light either in the morning or in the evening. To test this hypothesis, individual baseline markers of circadian rhythms will be assessed as well as CLOCK allele status. (3) Mechanism of Action (Mediators): Changes in the phase, amplitude, or degree of synchronization of circadian rhythm measures over treatment may account for some of
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the observed effects of treatment. To test this hypothesis, changes during treatment of markers of circadian rhythms will be assessed in related to changes in sleep during treatment. (4) Quality of Life: The research will determine whether bright light is an effective therapy for insomnia relative to HYG in terms of its impact on health-related quality of life. These hypotheses will be tested in a parallel-groups design with three conditions: HYG, HYG-AM LIGHT, and HYG+PM LIGHT. Daily treatments will last three months and after the end of treatment patients will be followed on a once-a-month basis for a period of three months. Measures will be taken prior to the beginning of treatment, at the end of treatment, and to document stability of treatment effect, some measures will be repeated once a month during the three-month follow-up period. This five-year application will ultimately include 90 treatment subjects aged >60 years (three groups of 30 each). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: YOGA AS A TREATMENT FOR INSOMNIA Principal Investigator & Institution: Khalsa, Sat B.; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2001; Project Start 18-SEP-2000; Project End 31-AUG-2005 Summary: (Applicant's Abstract): The purpose of this award is to provide support for a transition in career direction from basic research in circadian rhythms and sleep, to a long term goal of an established clinical research program evaluating effective alternative/complementary approaches in sleep disorders medicine. Immediate goals toward this end include training in clinical sleep disorders research. Participation in existing local training programs, courses, and seminars in the research fields of both sleep disorders and mind/body medicine will contribute to the career development plan. The main focus of this plan involves the completion of a research study to evaluate the effectiveness of yoga in treating insomnia. The primary sponsor of this award has a strong history of research in sleep disorders research whereas the cosponsor adds significant research experience in insomnia and the treatment of insomnia. The proposed collaborators will contribute additional expertise in insomnia and autonomic function. Brigham and Women's Hospital and the Harvard Medical area provide an ideal environment for research support and training in both sleep disorders and alternative medicine. Insomnia is a prevalent sleep disorder in which cognitive and/or physiological arousal associated with sustained sympathetic activation is one of the underlying causes. Treatments which address this arousal have been shown to be effective. Research studies have documented the effectiveness of yoga in reducing sympathetic activation and in the treatment of specific medical disorders. Although it has been used and recommended for the treatment of insomnia, its effectiveness has not been adequately evaluated. Subjective and objective measures of sleep and sympathovagal balance will be evaluated before and after a 2-month treatment in psychophysiological insomniacs randomized into yoga treatment and control groups. We anticipate that yoga will prove to be an effective insomnia treatment which reduces sympathovagal balance. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “insomnia” (or synonyms) into the search box. This search gives you access to fulltext articles. The following is a sample of items found for insomnia in the PubMed Central database: •
Discontinuation of benzodiazepines among older insomniac adults treated with cognitive-behavioural therapy combined with gradual tapering: a randomized trial. by Baillargeon L, Landreville P, Verreault R, Beauchemin JP, Gregoire JP, Morin CM.; 2003 Nov 11; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=236226
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Fatal Familial Insomnia and Familial Creutzfeldt-Jakob Disease: Different Prion Proteins Determined by a DNA Polymorphism. by Monari L, Chen SG, Brown P, Parchi P, Petersen RB, Mikol J, Gray F, Cortelli P, Montagna P, Ghetti B, Goldfarb LG, Gajdusek DC, Lugaresi E, Gambetti P, Autilio-Gambetti L.; 1994 Mar 29; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=43466
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Insomnia is a frequent finding in adults with Asperger syndrome. by Tani P, Lindberg N, Wendt TN, von Wendt L, Alanko L, Appelberg B, Porkka-Heiskanen T.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=270035
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Long term benzodiazepine use for insomnia in patients over the age of 60: discordance of patient and physician perceptions. by Mah L, Upshur RE.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=113266
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Treatment of primary insomnia with melatonin: a double-blind, placebo-controlled, crossover study. by Montes LG, Uribe MP, Sotres JC, Martin GH.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=161743
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Treatment of primary insomnia. by Montplaisir J.; 2000 Aug 22; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=80369
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Treatment of primary insomnia. by Holbrook A, Labiris R.; 2000 Aug 22; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=80370
The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 3 4
Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.
With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print. 6 PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction
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The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with insomnia, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “insomnia” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for insomnia (hyperlinks lead to article summaries): •
A cognitive model of insomnia. Author(s): Harvey AG. Source: Behaviour Research and Therapy. 2002 August; 40(8): 869-93. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12186352&dopt=Abstract
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A double-blind comparative study of zolpidem versus zopiclone in the treatment of chronic primary insomnia. Author(s): Tsutsui S; Zolipidem Study Group. Source: J Int Med Res. 2001 May-June; 29(3): 163-77. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11471853&dopt=Abstract
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A primary care “friendly” cognitive behavioral insomnia therapy. Author(s): Edinger JD, Sampson WS. Source: Sleep. 2003 March 15; 26(2): 177-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12683477&dopt=Abstract
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A psychiatric perspective on insomnia. Author(s): McCall WV. Source: The Journal of Clinical Psychiatry. 2001; 62 Suppl 10: 27-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11388587&dopt=Abstract
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Absence of sleep EEG markers in fatal familial insomnia healthy carriers: a spectral analysis study. Author(s): Ferrillo F, Plazzi G, Nobili L, Beelke M, De Carli F, Cortelli P, Tinuper P, Avoni P, Vandi S, Gambetti P, Lugaresi E, Montagna P. Source: Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. 2001 October; 112(10): 1888-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11595148&dopt=Abstract
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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Activity, arousal, and the MSLT in patients with insomnia. Author(s): Bonnet MH, Arand DL. Source: Sleep. 2000 March 15; 23(2): 205-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10737337&dopt=Abstract
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Acute efficacy of fluoxetine versus sertraline and paroxetine in major depressive disorder including effects of baseline insomnia. Author(s): Fava M, Hoog SL, Judge RA, Kopp JB, Nilsson ME, Gonzales JS. Source: Journal of Clinical Psychopharmacology. 2002 April; 22(2): 137-47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11910258&dopt=Abstract
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Advances in the behavioral treatment of insomnia. Author(s): Hauri PJ. Source: Sleep Medicine Reviews. 2003 June; 7(3): 201-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12927119&dopt=Abstract
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Adverse effects of temazepam in older adults with chronic insomnia. Author(s): Morin CM, Bastien CH, Brink D, Brown TR. Source: Human Psychopharmacology. 2003 January; 18(1): 75-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12532318&dopt=Abstract
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Alteration of the serotonergic nervous system in fatal familial insomnia. Author(s): Wanschitz J, Kloppel S, Jarius C, Birner P, Flicker H, Hainfellner JA, Gambetti P, Guentchev M, Budka H. Source: Annals of Neurology. 2000 November; 48(5): 788-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11079543&dopt=Abstract
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Alteration of the serotoninergic system in fatal familial insomnia. Author(s): Cortelli P, Polinsky R, Montagna P, Lugaresi E. Source: Annals of Neurology. 2001 September; 50(3): 421-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11558802&dopt=Abstract
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Ambulatory cassette polysomnography: findings from a large cohort of drug-free insomnia patients. Author(s): Edinger JD, Erwin CW, Fins AI, Marsh GR, Krystal AD. Source: Journal of Clinical Neurophysiology : Official Publication of the American Electroencephalographic Society. 1995 May; 12(3): 302-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11221789&dopt=Abstract
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Amyotrophic lateral sclerosis associated with insomnia and the aggravation of sleepdisordered breathing. Author(s): Takekawa H, Kubo J, Miyamoto T, Miyamoto M, Hirata K. Source: Psychiatry and Clinical Neurosciences. 2001 June; 55(3): 263-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11422868&dopt=Abstract
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An actigraphic comparison of sleep restriction and sleep hygiene treatments for insomnia in older adults. Author(s): Friedman L, Benson K, Noda A, Zarcone V, Wicks DA, O'Connell K, Brooks JO 3rd, Bliwise DL, Yesavage JA. Source: Journal of Geriatric Psychiatry and Neurology. 2000 Spring; 13(1): 17-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10753003&dopt=Abstract
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An epidemiological study of insomnia among the Japanese general population. Author(s): Kim K, Uchiyama M, Okawa M, Liu X, Ogihara R. Source: Sleep. 2000 February 1; 23(1): 41-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10678464&dopt=Abstract
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An epidemiological study on insomnia in an elderly Thai population. Author(s): Sukying C, Bhokakul V, Udomsubpayakul U. Source: J Med Assoc Thai. 2003 April; 86(4): 316-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12757075&dopt=Abstract
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An open-label trial of evidence-based cognitive behavior therapy for nightmares and insomnia in crime victims with PTSD. Author(s): Krakow B, Johnston L, Melendrez D, Hollifield M, Warner TD, ChavezKennedy D, Herlan MJ. Source: The American Journal of Psychiatry. 2001 December; 158(12): 2043-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11729023&dopt=Abstract
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An unsuccessful attempt to develop a single-item screen for insomnia in cancer patients. Author(s): Passik SD, Whitcomb LA, Kirsh KL, Theobald DE. Source: Journal of Pain and Symptom Management. 2003 March; 25(3): 284-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12614963&dopt=Abstract
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Anxiety sensitivity: predictor of sleep-related impairment and medication use in chronic insomnia. Author(s): Vincent N, Walker J. Source: Depression and Anxiety. 2001; 14(4): 238-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11754132&dopt=Abstract
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Anxiety, depression, and insomnia. Author(s): Larzelere MM, Wiseman P. Source: Primary Care. 2002 June; 29(2): 339-60, Vii. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12391715&dopt=Abstract
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Are changes in beliefs and attitudes about sleep related to sleep improvements in the treatment of insomnia? Author(s): Morin CM, Blais F, Savard J. Source: Behaviour Research and Therapy. 2002 July; 40(7): 741-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12074370&dopt=Abstract
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Are periodic leg movements during sleep (PLMS) responsible for sleep disruption in insomnia patients? Author(s): Karadeniz D, Ondze B, Besset A, Billiard M. Source: European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies. 2000 May; 7(3): 331-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10886318&dopt=Abstract
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Are there gender differences in objective and subjective sleep measures? A study of insomniacs and healthy controls. Author(s): Voderholzer U, Al-Shajlawi A, Weske G, Feige B, Riemann D. Source: Depression and Anxiety. 2003; 17(3): 162-72. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12768650&dopt=Abstract
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Are there gender differences in the prescribing of hypnotic medications for insomnia? Author(s): Brownlee K, Devins GM, Flanigan M, Fleming JA, Morehouse R, Moscovitch A, Plamondon J, Reinish L, Shapiro CM. Source: Human Psychopharmacology. 2003 January; 18(1): 69-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12532317&dopt=Abstract
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Article: Characteristics of patients referred to an insomnia clinic (R Mahendran). Author(s): Chung KF. Source: Singapore Med J. 2002 January; 43(1): 046; Author Reply 046. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12008779&dopt=Abstract
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Aspects of quality of life in persons with pre-lingual deafness using sign language: subjective wellbeing, ill-health symptoms, depression and insomnia. Author(s): Werngren-Elgstrom M, Dehlin O, Iwarsson S. Source: Archives of Gerontology and Geriatrics. 2003 July-August; 37(1): 13-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12849069&dopt=Abstract
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Assessment and diagnosis of insomnia in non-pharmacological intervention studies. Author(s): Martin JL, Ancoli-Israel S. Source: Sleep Medicine Reviews. 2002 October; 6(5): 379-406. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12531128&dopt=Abstract
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Assessment and management of insomnia. Author(s): Schenck CH, Mahowald MW, Sack RL. Source: Jama : the Journal of the American Medical Association. 2003 May 21; 289(19): 2475-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12759306&dopt=Abstract
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Association between mental health screening by self-report questionnaire and insomnia in medical students. Author(s): Loayza H MP, Ponte TS, Carvalho CG, Pedrotti MR, Nunes PV, Souza CM, Zanette CB, Voltolini S, Chaves ML. Source: Arquivos De Neuro-Psiquiatria. 2001 June; 59(2-A): 180-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11400021&dopt=Abstract
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Athens Insomnia Scale: validation of an instrument based on ICD-10 criteria. Author(s): Soldatos CR, Dikeos DG, Paparrigopoulos TJ. Source: Journal of Psychosomatic Research. 2000 June; 48(6): 555-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11033374&dopt=Abstract
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Behavioral and pharmacological therapies for late-life insomnia: a randomized controlled trial. Author(s): Morin CM, Colecchi C, Stone J, Sood R, Brink D. Source: Jama : the Journal of the American Medical Association. 1999 March 17; 281(11): 991-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10086433&dopt=Abstract
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Behavioral and pharmacological treatment for insomnia. Author(s): Lesser GT. Source: Jama : the Journal of the American Medical Association. 1999 September 22-29; 282(12): 1130; Author Reply 1130-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10501109&dopt=Abstract
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Behavioral and pharmacological treatment for insomnia. Author(s): Finucane TE. Source: Jama : the Journal of the American Medical Association. 1999 September 22-29; 282(12): 1130; Author Reply 1130-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10501108&dopt=Abstract
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Behavioral treatment for chronic insomnia. Author(s): Arnedt JT, Martin JL, Posner DA. Source: Medicine and Health, Rhode Island. 2002 March; 85(3): 90-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11917751&dopt=Abstract
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Behavioral treatment of chronic insomnia in psychiatrically ill patients. Author(s): Dashevsky BA, Kramer M. Source: The Journal of Clinical Psychiatry. 1998 December; 59(12): 693-9; Quiz 700-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9921709&dopt=Abstract
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Behavioral treatment of insomnia in older adults: an open clinical trial comparing two interventions. Author(s): Pallesen S, Nordhus IH, Kvale G, Nielsen GH, Havik OE, Johnsen BH, Skjotskift S. Source: Behaviour Research and Therapy. 2003 January; 41(1): 31-48. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12488118&dopt=Abstract
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Behavioral treatment of insomnia: a clinical case series study. Author(s): Perlis M, Aloia M, Millikan A, Boehmler J, Smith M, Greenblatt D, Giles D. Source: Journal of Behavioral Medicine. 2000 April; 23(2): 149-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10833677&dopt=Abstract
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Behavioral treatment of insomnia: the Wilford Hall Insomnia Program. Author(s): Hryshko-Mullen AS. Source: Military Medicine. 2000 March; 165(3): 200-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10741083&dopt=Abstract
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Behavioral treatment of insomnia: treatment outcome and the relevance of medical and psychiatric morbidity. Author(s): Perlis ML, Sharpe M, Smith MT, Greenblatt D, Giles D. Source: Journal of Behavioral Medicine. 2001 June; 24(3): 281-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11436547&dopt=Abstract
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Behaviour of insomniacs and implication for their management. Author(s): Estivill E. Source: Sleep Medicine Reviews. 2002 October; 6 Suppl 1: S3-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12607570&dopt=Abstract
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Benzodiazepine treatment of anxiety or insomnia in substance abuse patients. Author(s): Ciraulo DA, Nace EP. Source: The American Journal on Addictions / American Academy of Psychiatrists in Alcoholism and Addictions. 2000 Fall; 9(4): 276-9; Discussion 280-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11155783&dopt=Abstract
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Benzodiazepines and insomnia. Author(s): Finucane TE. Source: Journal of the American Geriatrics Society. 2002 April; 50(4): 775. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11982686&dopt=Abstract
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Benzodiazepines and related drugs for insomnia in palliative care. Author(s): Hirst A, Sloan R. Source: Cochrane Database Syst Rev. 2002; (4): Cd003346. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12519593&dopt=Abstract
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Best bets for managing insomnia: drug therapy, behavioral interventions. Author(s): Rollins G. Source: Rep Med Guidel Outcomes Res. 2001 April 5; 12(7): 10, 12. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12075628&dopt=Abstract
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Beta/Gamma EEG activity in patients with primary and secondary insomnia and good sleeper controls. Author(s): Perlis ML, Smith MT, Andrews PJ, Orff H, Giles DE. Source: Sleep. 2001 February 1; 24(1): 110-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11204046&dopt=Abstract
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Beta-CIT SPECT demonstrates reduced availability of serotonin transporters in patients with Fatal Familial Insomnia. Author(s): Kloppel S, Pirker W, Brucke T, Kovacs GG, Almer G. Source: Journal of Neural Transmission (Vienna, Austria : 1996). 2002 July; 109(7-8): 1105-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12111447&dopt=Abstract
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Brief report: melatonin facilitates sleep in individuals with mental retardation and insomnia. Author(s): Niederhofer H, Staffen W, Mair A, Pittschieler K. Source: Journal of Autism and Developmental Disorders. 2003 August; 33(4): 469-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12959427&dopt=Abstract
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Bright light treatment for night-time insomnia and daytime sleepiness in elderly people: comparison with a short-acting hypnotic. Author(s): Usui A, Ishizuka Y, Matsushita Y, Fukuzawa H, Kanba S. Source: Psychiatry and Clinical Neurosciences. 2000 June; 54(3): 374-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11186120&dopt=Abstract
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Can sleep be bad for you? Can insomnia be good? Author(s): Buysse DJ, Ganguli M. Source: Archives of General Psychiatry. 2002 February; 59(2): 137-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11825134&dopt=Abstract
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Can valerian improve the sleep of insomniacs after benzodiazepine withdrawal? Author(s): Poyares DR, Guilleminault C, Ohayon MM, Tufik S. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2002 April; 26(3): 539-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11999905&dopt=Abstract
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CAP variables and arousals as sleep electroencephalogram markers for primary insomnia. Author(s): Terzano MG, Parrino L, Spaggiari MC, Palomba V, Rossi M, Smerieri A. Source: Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. 2003 September; 114(9): 1715-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12948801&dopt=Abstract
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Cases from the Aerospace Medicine Resident's Teaching File. Low G-tolerance presenting as insomnia. Author(s): Rouse DM. Source: Aviation, Space, and Environmental Medicine. 2002 July; 73(7): 713-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12137112&dopt=Abstract
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Catastrophic worry in primary insomnia. Author(s): Harvey AG, Greenall E. Source: Journal of Behavior Therapy and Experimental Psychiatry. 2003 March; 34(1): 11-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12763390&dopt=Abstract
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Characteristics of insomnia in the United States: results of the 1991 National Sleep Foundation Survey. I. Author(s): Ancoli-Israel S, Roth T. Source: Sleep. 1999 May 1; 22 Suppl 2: S347-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10394606&dopt=Abstract
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Characteristics of patients referred to an insomnia clinic. Author(s): Mahendran R. Source: Singapore Med J. 2001 February; 42(2): 064-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11358193&dopt=Abstract
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Chronic insomnia and activity of the stress system: a preliminary study. Author(s): Vgontzas AN, Tsigos C, Bixler EO, Stratakis CA, Zachman K, Kales A, VelaBueno A, Chrousos GP. Source: Journal of Psychosomatic Research. 1998 July; 45(1 Spec No): 21-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9720852&dopt=Abstract
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Chronic insomnia in workers poisoned by inorganic mercury: psychological and adaptive aspects. Author(s): Rossini SR, Reimao R, Lefevre BH, Medrado-Faria MA. Source: Arquivos De Neuro-Psiquiatria. 2000 March; 58(1): 32-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10770863&dopt=Abstract
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Chronic insomnia is associated with a shift of interleukin-6 and tumor necrosis factor secretion from nighttime to daytime. Author(s): Vgontzas AN, Zoumakis M, Papanicolaou DA, Bixler EO, Prolo P, Lin HM, Vela-Bueno A, Kales A, Chrousos GP. Source: Metabolism: Clinical and Experimental. 2002 July; 51(7): 887-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12077736&dopt=Abstract
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Chronic insomnia is associated with nyctohemeral activation of the hypothalamicpituitary-adrenal axis: clinical implications. Author(s): Vgontzas AN, Bixler EO, Lin HM, Prolo P, Mastorakos G, Vela-Bueno A, Kales A, Chrousos GP. Source: The Journal of Clinical Endocrinology and Metabolism. 2001 August; 86(8): 3787-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11502812&dopt=Abstract
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Chronic insomnia, postmenopausal women, and sleep disordered breathing: part 1. Frequency of sleep disordered breathing in a cohort. Author(s): Guilleminault C, Palombini L, Poyares D, Chowdhuri S. Source: Journal of Psychosomatic Research. 2002 July; 53(1): 611-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12127179&dopt=Abstract
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Chronic insomnia, premenopausal women and sleep disordered breathing: part 2. Comparison of nondrug treatment trials in normal breathing and UARS post menopausal women complaining of chronic insomnia. Author(s): Guilleminault C, Palombini L, Poyares D, Chowdhuri S. Source: Journal of Psychosomatic Research. 2002 July; 53(1): 617-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12127180&dopt=Abstract
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Chronic insomnia: a practical review. Author(s): Rajput V, Bromley SM. Source: American Family Physician. 1999 October 1; 60(5): 1431-8; Discussion 1441-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10524487&dopt=Abstract
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Circadian phase estimation of chronic insomniacs relates to their sleep characteristics. Author(s): Kerkhof G, van Vianen B. Source: Archives of Physiology and Biochemistry. 1999 December; 107(5): 383-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10916166&dopt=Abstract
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Clinical significance and predictors of treatment response to cognitive-behavior therapy for insomnia secondary to chronic pain. Author(s): Currie SR, Wilson KG, Curran D. Source: Journal of Behavioral Medicine. 2002 April; 25(2): 135-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11977435&dopt=Abstract
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Cognitive behavioral therapy for treatment of chronic primary insomnia: a randomized controlled trial. Author(s): Edinger JD, Wohlgemuth WK, Radtke RA, Marsh GR, Quillian RE. Source: Jama : the Journal of the American Medical Association. 2001 April 11; 285(14): 1856-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11308399&dopt=Abstract
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Cognitive behaviour therapy for primary insomnia: can we rest yet? Author(s): Harvey AG, Tang NK. Source: Sleep Medicine Reviews. 2003 June; 7(3): 237-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12927123&dopt=Abstract
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Cognitive performance and sleep quality in the elderly suffering from chronic insomnia. Relationship between objective and subjective measures. Author(s): Bastien CH, Fortier-Brochu E, Rioux I, LeBlanc M, Daley M, Morin CM. Source: Journal of Psychosomatic Research. 2003 January; 54(1): 39-49. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12505554&dopt=Abstract
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Cognitive-behavioral treatment of insomnia secondary to chronic pain. Author(s): Currie SR, Wilson KG, Pontefract AJ, deLaplante L. Source: Journal of Consulting and Clinical Psychology. 2000 June; 68(3): 407-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10883557&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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Comparative meta-analysis of pharmacotherapy and behavior therapy for persistent insomnia. Author(s): Smith MT, Perlis ML, Park A, Smith MS, Pennington J, Giles DE, Buysse DJ. Source: The American Journal of Psychiatry. 2002 January; 159(1): 5-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11772681&dopt=Abstract
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Comparison of subjective and objective measures of insomnia in monozygotic twins discordant for chronic fatigue syndrome. Author(s): Watson NF, Kapur V, Arguelles LM, Goldberg J, Schmidt DF, Armitage R, Buchwald D. Source: Sleep. 2003 May 1; 26(3): 324-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12749553&dopt=Abstract
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Complaints of poststroke insomnia and its treatment with mianserin. Author(s): Palomaki H, Berg A, Meririnne E, Kaste M, Lonnqvist R, Lehtihalmes M, Lonnqvist J. Source: Cerebrovascular Diseases (Basel, Switzerland). 2003; 15(1-2): 56-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12499712&dopt=Abstract
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Complex insomnia: insomnia and sleep-disordered breathing in a consecutive series of crime victims with nightmares and PTSD. Author(s): Krakow B, Melendrez D, Pedersen B, Johnston L, Hollifield M, Germain A, Koss M, Warner TD, Schrader R. Source: Biological Psychiatry. 2001 June 1; 49(11): 948-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11377413&dopt=Abstract
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Consensus for the pharmacological management of insomnia in the new millennium. Author(s): Roth T, Hajak G, Ustun TB. Source: Int J Clin Pract. 2001 January-February; 55(1): 42-52. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11219318&dopt=Abstract
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Consequences of insomnia and its therapies. Author(s): Benca RM. Source: The Journal of Clinical Psychiatry. 2001; 62 Suppl 10: 33-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11388589&dopt=Abstract
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Continuous versus non-nightly use of zolpidem in chronic insomnia: results of a large-scale, double-blind, randomized, outpatient study. Author(s): Hajak G, Cluydts R, Declerck A, Estivill SE, Middleton A, Sonka K, Unden M. Source: International Clinical Psychopharmacology. 2002 January; 17(1): 9-17. Erratum In: Int Clin Psychopharmacol 2002 July; 17(4): 206. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11800507&dopt=Abstract
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Conventional and power spectrum analysis of the effects of zolpidem on sleep EEG in patients with chronic primary insomnia. Author(s): Monti JM, Alvarino F, Monti D. Source: Sleep. 2000 December 15; 23(8): 1075-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11145322&dopt=Abstract
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Core body temperature and sleep of older female insomniacs before and after passive body heating. Author(s): Dorsey CM, Teicher MH, Cohen-Zion M, Stefanovic L, Satlin A, Tartarini W, Harper D, Lukas SE. Source: Sleep. 1999 November 1; 22(7): 891-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10566907&dopt=Abstract
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Daytime consequences and correlates of insomnia in the United States: results of the 1991 National Sleep Foundation Survey. II. Author(s): Roth T, Ancoli-Israel S. Source: Sleep. 1999 May 1; 22 Suppl 2: S354-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10394607&dopt=Abstract
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Daytime testing after laboratory or home-based polysomnography: comparisons of middle-aged insomnia sufferers and normal sleepers. Author(s): Edinger JD, Glenn DM, Bastian LA, Marsh GR, Dailey D, Hope TV, Young M, Shaw E, Meeks G. Source: Journal of Sleep Research. 2003 March; 12(1): 43-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12603786&dopt=Abstract
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Depression and insomnia. Author(s): Morawetz D. Source: Aust Fam Physician. 2000 November; 29(11): 1016. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11127055&dopt=Abstract
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Detecting insomnia: comparison of four self-report measures of sleep in a young adult population. Author(s): Smith S, Trinder J. Source: Journal of Sleep Research. 2001 September; 10(3): 229-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11696076&dopt=Abstract
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Detection of insomnia in primary care. Author(s): Doghramji PP. Source: The Journal of Clinical Psychiatry. 2001; 62 Suppl 10: 18-26. Review. Erratum In: J Clin Psychiatry 2001 August; 62(8): 658. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11388586&dopt=Abstract
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Development of an adjective checklist to measure five FACES of fatigue and sleepiness. Data from a national survey of insomniacs. Author(s): Shapiro CM, Flanigan M, Fleming JA, Morehouse R, Moscovitch A, Plamondon J, Reinish L, Devins GM. Source: Journal of Psychosomatic Research. 2002 June; 52(6): 467-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12069871&dopt=Abstract
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Diagnose and treat primary insomnia. Author(s): Cochran H. Source: The Nurse Practitioner. 2003 September; 28(9): 13-27; Quiz 27-29. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14501552&dopt=Abstract
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Diagnosis and management of insomnia. Author(s): Roth T. Source: Clinical Cornerstone. 2000; 2(5): 28-38. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10875044&dopt=Abstract
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Diagnosis and treatment of insomnia. Author(s): Bonnet MH, Arand DL. Source: Respir Care Clin N Am. 1999 September; 5(3): 333-48, Vii. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10419579&dopt=Abstract
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Differential effects of nefazodone and cognitive behavioral analysis system of psychotherapy on insomnia associated with chronic forms of major depression. Author(s): Thase ME, Rush AJ, Manber R, Kornstein SG, Klein DN, Markowitz JC, Ninan PT, Friedman ES, Dunner DL, Schatzberg AF, Borian FE, Trivedi MH, Keller MB. Source: The Journal of Clinical Psychiatry. 2002 June; 63(6): 493-500. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12088160&dopt=Abstract
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Differential rates of psychopathology symptoms in periodic limb movement disorder, obstructive sleep apnea, psychophysiological insomnia, and insomnia with psychiatric disorder. Author(s): Aikens JE, Vanable PA, Tadimeti L, Caruana-Montaldo B, Mendelson WB. Source: Sleep. 1999 September 15; 22(6): 775-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10505823&dopt=Abstract
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Does cognitive-behavioral insomnia therapy alter dysfunctional beliefs about sleep? Author(s): Edinger JD, Wohlgemuth WK, Radtke RA, Marsh GR, Quillian RE. Source: Sleep. 2001 August 1; 24(5): 591-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11480656&dopt=Abstract
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Does the prion protein gene 129 codon polymorphism influence sleep? Evidence from a fatal familial insomnia kindred. Author(s): Plazzi G, Montagna P, Beelke M, Nobili L, De Carli F, Cortelli P, Vandi S, Avoni P, Tinuper P, Gambetti P, Lugaresi E, Ferrillo F. Source: Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. 2002 December; 113(12): 1948-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12464332&dopt=Abstract
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Doxepin in the treatment of primary insomnia: a placebo-controlled, double-blind, polysomnographic study. Author(s): Hajak G, Rodenbeck A, Voderholzer U, Riemann D, Cohrs S, Hohagen F, Berger M, Ruther E. Source: The Journal of Clinical Psychiatry. 2001 June; 62(6): 453-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11465523&dopt=Abstract
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Dreaming and insomnia: dream recall and dream content of patients with insomnia. Author(s): Schredl M, Schafer G, Weber B, Heuser I. Source: Journal of Sleep Research. 1998 September; 7(3): 191-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9785274&dopt=Abstract
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Drug treatment of patients with insomnia and excessive daytime sleepiness: pharmacokinetic considerations. Author(s): Nishino S, Mignot E. Source: Clinical Pharmacokinetics. 1999 October; 37(4): 305-30. Review. Erratum In: Clin Pharmacokinet 2000 January; 38(1): 40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10554047&dopt=Abstract
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Dysautonomia in fatal familial insomnia as an indicator of the potential role of the thalamus in autonomic control. Author(s): Benarroch EE, Stotz-Potter EH. Source: Brain Pathology (Zurich, Switzerland). 1998 July; 8(3): 527-30. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9669703&dopt=Abstract
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Effect of a fixed valerian-Hop extract combination (Ze 91019) on sleep polygraphy in patients with non-organic insomnia: a pilot study. Author(s): Fussel A, Wolf A, Brattstrom A. Source: European Journal of Medical Research. 2000 September 18; 5(9): 385-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11003973&dopt=Abstract
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Effect of the prion 129 polymorphism on nocturnal sleep and insomnia complaints: a population-based study. Author(s): Pedrazzoli M, Ling L, Young TB, Finn L, Tufik S, Mignot E. Source: Journal of Sleep Research. 2002 December; 11(4): 357-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12464104&dopt=Abstract
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Effects of chronic insomnia and use of benzodiazepines on daytime performance in older adults. Author(s): Vignola A, Lamoureux C, Bastien CH, Morin CM. Source: The Journals of Gerontology. Series B, Psychological Sciences and Social Sciences. 2000 January; 55(1): P54-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10728124&dopt=Abstract
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Effects of hormone replacement therapy on perceptual and cognitive event-related potentials in menopausal insomnia. Author(s): Anderer P, Semlitsch HV, Saletu B, Saletu-Zyhlarz G, Gruber D, Metka M, Huber J, Graser T, Oettel M. Source: Psychoneuroendocrinology. 2003 April; 28(3): 419-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12573306&dopt=Abstract
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Effects of reboxetine on anxiety, agitation, and insomnia: results of a pooled evaluation of randomized clinical trials. Author(s): Stahl SM, Mendels J, Schwartz GE. Source: Journal of Clinical Psychopharmacology. 2002 August; 22(4): 388-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12172338&dopt=Abstract
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Effects of sleep deprivation on daytime sleepiness in primary insomnia. Author(s): Stepanski E, Zorick F, Roehrs T, Roth T. Source: Sleep. 2000 March 15; 23(2): 215-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10737338&dopt=Abstract
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Efficacy and tolerability of valerian extract LI 156 compared with oxazepam in the treatment of non-organic insomnia--a randomized, double-blind, comparative clinical study. Author(s): Ziegler G, Ploch M, Miettinen-Baumann A, Collet W. Source: European Journal of Medical Research. 2002 November 25; 7(11): 480-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12568976&dopt=Abstract
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Efficacy of cognitive-behavioral therapy for insomnia in women treated for nonmetastatic breast cancer. Author(s): Quesnel C, Savard J, Simard S, Ivers H, Morin CM. Source: Journal of Consulting and Clinical Psychology. 2003 February; 71(1): 189-200. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12602439&dopt=Abstract
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Efficacy of two behavioral treatment programs for comorbid geriatric insomnia. Author(s): Rybarczyk B, Lopez M, Benson R, Alsten C, Stepanski E. Source: Psychology and Aging. 2002 June; 17(2): 288-98. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12061413&dopt=Abstract
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Eight weeks of non-nightly use of zolpidem for primary insomnia. Author(s): Walsh JK, Roth T, Randazzo A, Erman M, Jamieson A, Scharf M, Schweitzer PK, Ware JC. Source: Sleep. 2000 December 15; 23(8): 1087-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11145323&dopt=Abstract
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Electroconvulsive therapy and cardiovascular complications in patients taking trazodone for insomnia. Author(s): Krahn LE, Hanson CA, Pileggi TS, Rummans TA. Source: The Journal of Clinical Psychiatry. 2001 February; 62(2): 108-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11247094&dopt=Abstract
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Epidemiology of insomnia: what we know and what we still need to learn. Author(s): Ohayon MM. Source: Sleep Medicine Reviews. 2002 April; 6(2): 97-111. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12531146&dopt=Abstract
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Epidemiology of severe insomnia and its consequences in Germany. Author(s): Hajak G; SINE Study Group. Study of Insomnia in Europe. Source: European Archives of Psychiatry and Clinical Neuroscience. 2001; 251(2): 49-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11407438&dopt=Abstract
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Evaluation and management of insomnia in menopause. Author(s): Jones CR, Czajkowski L. Source: Clinical Obstetrics and Gynecology. 2000 March; 43(1): 184-97. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10694999&dopt=Abstract
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Evaluation of chronic insomnia. An American Academy of Sleep Medicine review. Author(s): Sateia MJ, Doghramji K, Hauri PJ, Morin CM. Source: Sleep. 2000 March 15; 23(2): 243-308. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10737342&dopt=Abstract
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Evaluation of severe insomnia in the general population: results of a European multinational survey. Author(s): Chevalier H, Los F, Boichut D, Bianchi M, Nutt DJ, Hajak G, Hetta J, Hoffmann G, Crowe C. Source: Journal of Psychopharmacology (Oxford, England). 1999; 13(4 Suppl 1): S21-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10667452&dopt=Abstract
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Evaluation of severe insomnia in the general population--implications for the management of insomnia: focus on results from Belgium. Author(s): Hoffmann G. Source: Journal of Psychopharmacology (Oxford, England). 1999; 13(4 Suppl 1): S31-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10667456&dopt=Abstract
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Evaluation of severe insomnia in the general population--implications for the management of insomnia: focus on results from Ireland. Author(s): Crowe C. Source: Journal of Psychopharmacology (Oxford, England). 1999; 13(4 Suppl 1): S29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10667454&dopt=Abstract
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Evaluation of severe insomnia in the general population--implications for the management of insomnia: insomnia, quality of life and healthcare consumption in Sweden. Author(s): Hetta J, Broman JE, Mallon L. Source: Journal of Psychopharmacology (Oxford, England). 1999; 13(4 Suppl 1): S35-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10667458&dopt=Abstract
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Evaluation of severe insomnia in the general population--implications for the management of insomnia: the German perspective. Author(s): Hajak G. Source: Journal of Psychopharmacology (Oxford, England). 1999; 13(4 Suppl 1): S30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10667455&dopt=Abstract
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Evaluation of severe insomnia in the general population--implications for the management of insomnia: the UK perspective. Author(s): Nutt DJ, Wilson S. Source: Journal of Psychopharmacology (Oxford, England). 1999; 13(4 Suppl 1): S33-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10667457&dopt=Abstract
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Event-related current density in primary insomnia. Author(s): Szelenberger W, Niemcewicz S. Source: Acta Neurobiol Exp (Wars). 2001; 61(4): 299-308. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11905151&dopt=Abstract
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Evidence based complementary intervention for insomnia. Author(s): Lopez HH, Bracha AS, Bracha HS. Source: Hawaii Med J. 2002 September; 61(9): 192, 213. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12422383&dopt=Abstract
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Experience in differentiation and treatment of stubborn insomnia. Author(s): Qian Y. Source: J Tradit Chin Med. 2001 September; 21(3): 168-73. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11789318&dopt=Abstract
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Factor structure and measurement invariance of the Women's Health Initiative Insomnia Rating Scale. Author(s): Levine DW, Kaplan RM, Kripke DF, Bowen DJ, Naughton MJ, Shumaker SA. Source: Psychological Assessment. 2003 June; 15(2): 123-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12847773&dopt=Abstract
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Factors associated with insomnia among post-acute traumatic brain injury survivors. Author(s): Fichtenberg NL, Millis SR, Mann NR, Zafonte RD, Millard AE. Source: Brain Injury : [bi]. 2000 July; 14(7): 659-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10914647&dopt=Abstract
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Failure of timed bright light exposure to alleviate age-related sleep maintenance insomnia. Author(s): Suhner AG, Murphy PJ, Campbell SS. Source: Journal of the American Geriatrics Society. 2002 April; 50(4): 617-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11982660&dopt=Abstract
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Familial and sporadic fatal insomnia. Author(s): Montagna P, Gambetti P, Cortelli P, Lugaresi E. Source: Lancet. Neurology. 2003 March; 2(3): 167-76. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12849238&dopt=Abstract
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Familial Creutzfeldt-Jakob disease with D178N-129M mutation of PRNP presenting as cerebellar ataxia without insomnia. Author(s): Taniwaki Y, Hara H, Doh-Ura K, Murakami I, Tashiro H, Yamasaki T, Shigeto H, Arakawa K, Araki E, Yamada T, Iwaki T, Kira J. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2000 March; 68(3): 388. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10787305&dopt=Abstract
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Familial incidence of insomnia. Author(s): Bastien CH, Morin CM. Source: Journal of Sleep Research. 2000 March; 9(1): 49-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10733689&dopt=Abstract
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Fatal familial insomnia around the world. Introduction. Author(s): Budka H. Source: Brain Pathology (Zurich, Switzerland). 1998 July; 8(3): 553. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9669707&dopt=Abstract
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Fatal familial insomnia in a new Italian kindred. Author(s): Padovani A, D'Alessandro M, Parchi P, Cortelli P, Anzola GP, Montagna P, Vignolo LA, Petraroli R, Pocchiari M, Lugaresi E, Gambetti P. Source: Neurology. 1998 November; 51(5): 1491-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9818894&dopt=Abstract
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Fatal familial insomnia: a new Austrian family. Author(s): Almer G, Hainfellner JA, Brucke T, Jellinger K, Kleinert R, Bayer G, Windl O, Kretzschmar HA, Hill A, Sidle K, Collinge J, Budka H. Source: Brain; a Journal of Neurology. 1999 January; 122 ( Pt 1): 5-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10050890&dopt=Abstract
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Fatal familial insomnia: clinical and pathologic heterogeneity in genetic half brothers. Author(s): Johnson MD, Vnencak-Jones CL, McLean MJ. Source: Neurology. 1998 December; 51(6): 1715-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9855529&dopt=Abstract
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Fatal familial insomnia: clinical features and molecular genetics. Author(s): Cortelli P, Gambetti P, Montagna P, Lugaresi E. Source: Journal of Sleep Research. 1999 June; 8 Suppl 1: 23-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10389103&dopt=Abstract
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Fatal familial insomnia: clinical, neuropathological, and genetic description of a Spanish family. Author(s): Tabernero C, Polo JM, Sevillano MD, Munoz R, Berciano J, Cabello A, Baez B, Ricoy JR, Carpizo R, Figols J, Cuadrado N, Claveria LE. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2000 June; 68(6): 774-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10811705&dopt=Abstract
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Future directions in the management of insomnia. Author(s): Richardson GS, Roth T. Source: The Journal of Clinical Psychiatry. 2001; 62 Suppl 10: 39-45. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11388590&dopt=Abstract
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Gabapentin treatment for insomnia associated with alcohol dependence. Author(s): Karam-Hage M, Brower KJ. Source: The American Journal of Psychiatry. 2000 January; 157(1): 151. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10618048&dopt=Abstract
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Gender differences in insomnia--a study in the Hong Kong Chinese population. Author(s): Li RH, Wing YK, Ho SC, Fong SY. Source: Journal of Psychosomatic Research. 2002 July; 53(1): 601-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12127178&dopt=Abstract
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Genetic dissection of psychopathological symptoms: insomnia in mood disorders and CLOCK gene polymorphism. Author(s): Serretti A, Benedetti F, Mandelli L, Lorenzi C, Pirovano A, Colombo C, Smeraldi E. Source: American Journal of Medical Genetics. 2003 August 15; 121B(1): 35-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12898572&dopt=Abstract
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Gerstmann-Straussler-Scheinker syndrome,fatal familial insomnia, and kuru: a review of these less common human transmissible spongiform encephalopathies. Author(s): Collins S, McLean CA, Masters CL. Source: Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia. 2001 September; 8(5): 387-97. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11535002&dopt=Abstract
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Heart rate variability in insomniacs and matched normal sleepers. Author(s): Bonnet MH, Arand DL. Source: Psychosomatic Medicine. 1998 September-October; 60(5): 610-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9773766&dopt=Abstract
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Helping patients who say they cannot sleep. Practical ways to evaluate and treat insomnia. Author(s): Attarian HP. Source: Postgraduate Medicine. 2000 March; 107(3): 127-30, 133-7, 140-2. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10728140&dopt=Abstract
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Herbal treatment of insomnia. Author(s): Wing YK. Source: Hong Kong Medical Journal = Xianggang Yi Xue Za Zhi / Hong Kong Academy of Medicine. 2001 December; 7(4): 392-402. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11773674&dopt=Abstract
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High prevalence of insomnia in an outpatient population with HIV infection. Author(s): Rubinstein ML, Selwyn PA. Source: Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology : Official Publication of the International Retrovirology Association. 1998 November 1; 19(3): 260-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9803968&dopt=Abstract
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Higher efavirenz plasma levels correlate with development of insomnia. Author(s): Nunez M, Gonzalez de Requena D, Gallego L, Jimenez-Nacher I, GonzalezLahoz J, Soriano V. Source: Journal of Acquired Immune Deficiency Syndromes (1999). 2001 December 1; 28(4): 399-400. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11707679&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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Hospitalized patients' preference in the treatment of insomnia: pharmacological versus non-pharmacological. Author(s): Azad N, Byszewski A, Sarazin FF, McLean W, Koziarz P. Source: Can J Clin Pharmacol. 2003 Summer; 10(2): 89-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12879147&dopt=Abstract
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How age and daytime activities are related to insomnia in the general population: consequences for older people. Author(s): Ohayon MM, Zulley J, Guilleminault C, Smirne S, Priest RG. Source: Journal of the American Geriatrics Society. 2001 April; 49(4): 360-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11347777&dopt=Abstract
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How many nights are enough? The short-term stability of sleep parameters in elderly insomniacs and normal sleepers. Author(s): Wohlgemuth WK, Edinger JD, Fins AI, Sullivan RJ Jr. Source: Psychophysiology. 1999 March; 36(2): 233-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10194970&dopt=Abstract
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How useful is cognitive behavioral therapy (CBT) for the treatment of chronic insomnia? Author(s): Phillips TG, Holdsworth J, Cook S. Source: The Journal of Family Practice. 2001 July; 50(7): 569. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11485698&dopt=Abstract
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Hypercalcemia and insomnia in hemodialysis patients. Author(s): Virga G, Stanic L, Mastrosimone S, Gastaldon F, da Porto A, Bonadonna A. Source: Nephron. 2000 May; 85(1): 94-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10773764&dopt=Abstract
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Individualizing therapy for early, middle-of-the-night and late-night insomnia. Author(s): Scharf MB. Source: Int J Clin Pract Suppl. 2001 January; (116): 20-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11219329&dopt=Abstract
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Insomnia and alpha sleep in chronic non-organic pain as compared to primary insomnia. Author(s): Schneider-Helmert D, Whitehouse I, Kumar A, Lijzenga C. Source: Neuropsychobiology. 2001 January; 43(1): 54-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11150900&dopt=Abstract
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Insomnia and cognitive decline. Author(s): Finucane TE. Source: Journal of the American Geriatrics Society. 2002 September; 50(9): 1604-5; Discussion 1605. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12383169&dopt=Abstract
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Insomnia and fronto-basal tumor: a case report. Author(s): Szucs A, Bodizs R, Barsi P, Halasz P. Source: European Neurology. 2001; 46(1): 54-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11455188&dopt=Abstract
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Insomnia and global sleep dissatisfaction in Finland. Author(s): Ohayon MM, Partinen M. Source: Journal of Sleep Research. 2002 December; 11(4): 339-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12464102&dopt=Abstract
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Insomnia and hypnotic use in Campo Grande general population, Brazil. Author(s): Souza JC, Magna LA, Reimao R. Source: Arquivos De Neuro-Psiquiatria. 2002 September; 60(3-B): 702-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12364933&dopt=Abstract
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Insomnia as an interaction between sleep-interfering and sleep-interpreting processes. Author(s): Lundh LG, Broman JE. Source: Journal of Psychosomatic Research. 2000 November; 49(5): 299-310. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11164054&dopt=Abstract
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Insomnia in children. Author(s): Navelet Y, Chambry J, Ferrari P. Source: Suppl Clin Neurophysiol. 2000; 53: 355-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12741019&dopt=Abstract
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Insomnia in men-a 10-year prospective population based study. Author(s): Janson C, Lindberg E, Gislason T, Elmasry A, Boman G. Source: Sleep. 2001 June 15; 24(4): 425-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11403527&dopt=Abstract
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Insomnia in the context of cancer: a review of a neglected problem. Author(s): Savard J, Morin CM. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2001 February 1; 19(3): 895-908. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11157043&dopt=Abstract
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Insomnia in the elderly: a review for the primary care practitioner. Author(s): Ancoli-Israel S. Source: Sleep. 2000 February 1; 23 Suppl 1: S23-30; Discussion S36-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10755805&dopt=Abstract
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Insomnia on dialysis nights. Author(s): Parker KP. Source: Seminars in Dialysis. 2003 January-February; 16(1): 77-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12535307&dopt=Abstract
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Insomnia screening in postacute traumatic brain injury: utility and validity of the Pittsburgh Sleep Quality Index. Author(s): Fictenberg NL, Putnam SH, Mann NR, Zafonte RD, Millard AE. Source: American Journal of Physical Medicine & Rehabilitation / Association of Academic Physiatrists. 2001 May; 80(5): 339-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11327555&dopt=Abstract
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Insomnia, fatigue, anxiety, depression, and quality of life of cancer patients undergoing chemotherapy. Author(s): Redeker NS, Lev EL, Ruggiero J. Source: Sch Inq Nurs Pract. 2000 Winter; 14(4): 275-90; Discussion 291-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11372188&dopt=Abstract
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Insomnia, metabolic rate and sleep restoration. Author(s): Bonnet MH, Arand DL. Source: Journal of Internal Medicine. 2003 July; 254(1): 23-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12823640&dopt=Abstract
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Insomnia, self-medication, and relapse to alcoholism. Author(s): Brower KJ, Aldrich MS, Robinson EA, Zucker RA, Greden JF. Source: The American Journal of Psychiatry. 2001 March; 158(3): 399-404. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11229980&dopt=Abstract
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Insomnia. Author(s): Epstein DR, Bootzin RR. Source: Nurs Clin North Am. 2002 December; 37(4): 611-31. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12587364&dopt=Abstract
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Insomnia. Diagnosis and management. Author(s): Grunstein R. Source: Aust Fam Physician. 2002 November; 31(11): 995-1000. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12471955&dopt=Abstract
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Insomniac artists explore night's terrain. Author(s): Lamberg L. Source: Jama : the Journal of the American Medical Association. 2003 May 7; 289(17): 2200-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734119&dopt=Abstract
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Intractable insomnia after cessation of treatment with thalidomide. Author(s): Fox MR, Harris A. Source: Gastroenterology. 2001 May; 120(6): 1567-8. Erratum In: Gastroenterology 2001 September; 121(3): 747. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11339241&dopt=Abstract
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JAMA patient page. Insomnia. Author(s): Parmet S, Lynm C, Glass RM. Source: Jama : the Journal of the American Medical Association. 2003 May 21; 289(19): 2602. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12759329&dopt=Abstract
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Kava and valerian in the treatment of stress-induced insomnia. Author(s): Wheatley D. Source: Phytotherapy Research : Ptr. 2001 September; 15(6): 549-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11536390&dopt=Abstract
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Lack of residual sedation following middle-of-the-night zaleplon administration in sleep maintenance insomnia. Author(s): Walsh JK, Pollak CP, Scharf MB, Schweitzer PK, Vogel GW. Source: Clinical Neuropharmacology. 2000 January-February; 23(1): 17-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10682226&dopt=Abstract
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Lamotrigine associated with insomnia. Author(s): Sadler M. Source: Epilepsia. 1999 March; 40(3): 322-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10080513&dopt=Abstract
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Limitations on the use of benzodiazepines in anxiety and insomnia: are they justified? Author(s): Lader MH. Source: European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology. 1999 December; 9 Suppl 6: S399-405. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10622686&dopt=Abstract
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Long-term effectiveness of a short-term cognitive-behavioral group treatment for primary insomnia. Author(s): Backhaus J, Hohagen F, Voderholzer U, Riemann D. Source: European Archives of Psychiatry and Clinical Neuroscience. 2001; 251(1): 35-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11315517&dopt=Abstract
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Major depression and insomnia in chronic pain. Author(s): Wilson KG, Eriksson MY, D'Eon JL, Mikail SF, Emery PC. Source: The Clinical Journal of Pain. 2002 March-April; 18(2): 77-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11882770&dopt=Abstract
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Management of chronic insomnia in the elderly. Author(s): Ring D. Source: Clin Excell Nurse Pract. 2001; 5(1): 13-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11154388&dopt=Abstract
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Management of insomnia in patients with chronic obstructive pulmonary disease. Author(s): George CF, Bayliff CD. Source: Drugs. 2003; 63(4): 379-87. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12558460&dopt=Abstract
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Management of insomnia--the role of zaleplon. Author(s): Richardson GS, Roth T, Kramer JA. Source: Medgenmed [electronic Resource] : Medscape General Medicine. 2002 March 14; 4(1): 9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11965211&dopt=Abstract
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Managing insomnia in the primary care setting: raising the issues. Author(s): Richardson GS. Source: Sleep. 2000 February 1; 23 Suppl 1: S9-12; Discussion S13-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10755803&dopt=Abstract
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Measuring outcomes in randomized clinical trials of insomnia treatments. Author(s): Morin CM. Source: Sleep Medicine Reviews. 2003 June; 7(3): 263-79. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12927124&dopt=Abstract
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Medical and socio-professional impact of insomnia. Author(s): Leger D, Guilleminault C, Bader G, Levy E, Paillard M. Source: Sleep. 2002 September 15; 25(6): 625-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12224841&dopt=Abstract
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Medication use in the treatment of pediatric insomnia: results of a survey of community-based pediatricians. Author(s): Owens JA, Rosen CL, Mindell JA. Source: Pediatrics. 2003 May; 111(5 Pt 1): E628-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12728122&dopt=Abstract
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Melatonin add-on in manic patients with treatment resistant insomnia. Author(s): Bersani G, Garavini A. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2000 February; 24(2): 185-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10800742&dopt=Abstract
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Melatonin as a chronobiotic for circadian insomnia. Clinical observations and animal models. Author(s): Armstrong SM. Source: Advances in Experimental Medicine and Biology. 1999; 460: 283-97. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10810524&dopt=Abstract
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Melatonin for chronic sleep onset insomnia in children: a randomized placebocontrolled trial. Author(s): Smits MG, Nagtegaal EE, van der Heijden J, Coenen AM, Kerkhof GA. Source: Journal of Child Neurology. 2001 February; 16(2): 86-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11292231&dopt=Abstract
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Melatonin in children and adolescents with insomnia: a retrospective study. Author(s): Ivanenko A, Crabtree VM, Tauman R, Gozal D. Source: Clinical Pediatrics. 2003 January-February; 42(1): 51-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12635982&dopt=Abstract
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Melatonin in elderly patients with insomnia. A systematic review. Author(s): Olde Rikkert MG, Rigaud AS. Source: Zeitschrift Fur Gerontologie Und Geriatrie : Organ Der Deutschen Gesellschaft Fur Gerontologie Und Geriatrie. 2001 December; 34(6): 491-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11828891&dopt=Abstract
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Melatonin in medically ill patients with insomnia: a double-blind, placebo-controlled study. Author(s): Andrade C, Srihari BS, Reddy KP, Chandramma L. Source: The Journal of Clinical Psychiatry. 2001 January; 62(1): 41-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11235927&dopt=Abstract
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Melatonin therapy: from benzodiazepine-dependent insomnia to authenticity and autonomy. Author(s): Bursztajn HJ. Source: Archives of Internal Medicine. 1999 November 8; 159(20): 2393-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10665885&dopt=Abstract
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Melatonin treatment for age-related insomnia. Author(s): Zhdanova IV, Wurtman RJ, Regan MM, Taylor JA, Shi JP, Leclair OU. Source: The Journal of Clinical Endocrinology and Metabolism. 2001 October; 86(10): 4727-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11600532&dopt=Abstract
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Meta-analysis of benzodiazepine use in the treatment of insomnia. Author(s): Holbrook AM, Crowther R, Lotter A, Cheng C, King D. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 2000 January 25; 162(2): 225-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10674059&dopt=Abstract
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Mirtazapine may be useful in treating nausea and insomnia of cancer chemotherapy. Author(s): Kast RE. Source: Supportive Care in Cancer : Official Journal of the Multinational Association of Supportive Care in Cancer. 2001 September; 9(6): 469-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11585276&dopt=Abstract
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Mismatch negativity and personality traits in chronic primary insomniacs. Author(s): Wang W, Zhu SZ, Pan LC, Hu AH, Wang YH. Source: Funct Neurol. 2001 January-March; 16(1): 3-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11396269&dopt=Abstract
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Mortality associated with sleep duration and insomnia. Author(s): Kripke DF, Garfinkel L, Wingard DL, Klauber MR, Marler MR. Source: Archives of General Psychiatry. 2002 February; 59(2): 131-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11825133&dopt=Abstract
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Neuroendocrine dysregulation in primary insomnia. Author(s): Rodenbeck A, Hajak G. Source: Revue Neurologique. 2001 November; 157(11 Pt 2): S57-61. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11924040&dopt=Abstract
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Neuroimaging of NREM sleep in primary insomnia: a Tc-99-HMPAO single photon emission computed tomography study. Author(s): Smith MT, Perlis ML, Chengazi VU, Pennington J, Soeffing J, Ryan JM, Giles DE. Source: Sleep. 2002 May 1; 25(3): 325-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12003163&dopt=Abstract
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Neuronal apoptosis in fatal familial insomnia. Author(s): Dorandeu A, Wingertsmann L, Chretien F, Delisle MB, Vital C, Parchi P, Montagna P, Lugaresi E, Ironside JW, Budka H, Gambetti P, Gray F. Source: Brain Pathology (Zurich, Switzerland). 1998 July; 8(3): 531-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9669704&dopt=Abstract
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New drugs for insomnia: comparative tolerability of zopiclone, zolpidem and zaleplon. Author(s): Terzano MG, Rossi M, Palomba V, Smerieri A, Parrino L. Source: Drug Safety : an International Journal of Medical Toxicology and Drug Experience. 2003; 26(4): 261-82. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12608888&dopt=Abstract
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New perspectives on the pharmacologic management of insomnia. Author(s): Roth T. Source: Int J Clin Pract Suppl. 2001 January; (116): 2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11219328&dopt=Abstract
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New trends in insomnia management. Author(s): Roth T. Source: Journal of Psychopharmacology (Oxford, England). 1999; 13(4 Suppl 1): S37-40. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10667459&dopt=Abstract
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Nocturnal catecholamines and immune function in insomniacs, depressed patients, and control subjects. Author(s): Irwin M, Clark C, Kennedy B, Christian Gillin J, Ziegler M. Source: Brain, Behavior, and Immunity. 2003 October; 17(5): 365-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12946658&dopt=Abstract
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Nocturnal cortisol and melatonin secretion in primary insomnia. Author(s): Riemann D, Klein T, Rodenbeck A, Feige B, Horny A, Hummel R, Weske G, Al-Shajlawi A, Voderholzer U. Source: Psychiatry Research. 2002 December 15; 113(1-2): 17-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12467942&dopt=Abstract
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Noise-induced sleep maintenance insomnia: hypnotic and residual effects of zaleplon. Author(s): Stone BM, Turner C, Mills SL, Paty I, Patat A, Darwish M, Danjou P. Source: British Journal of Clinical Pharmacology. 2002 February; 53(2): 196-202. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11851645&dopt=Abstract
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Nonpharmacologic group treatment of insomnia: a preliminary study with cancer survivors. Author(s): Davidson JR, Waisberg JL, Brundage MD, MacLean AW. Source: Psycho-Oncology. 2001 September-October; 10(5): 389-97. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11536417&dopt=Abstract
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Nonpharmacologic treatment of chronic insomnia. An American Academy of Sleep Medicine review. Author(s): Morin CM, Hauri PJ, Espie CA, Spielman AJ, Buysse DJ, Bootzin RR. Source: Sleep. 1999 December 15; 22(8): 1134-56. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10617176&dopt=Abstract
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Non-pharmacological management of primary and secondary insomnia among older people: review of assessment tools and treatments. Author(s): Petit L, Azad N, Byszewski A, Sarazan FF, Power B. Source: Age and Ageing. 2003 January; 32(1): 19-25. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12540343&dopt=Abstract
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Nonpharmacological treatment of late-life insomnia. Author(s): Morin CM, Mimeault V, Gagne A. Source: Journal of Psychosomatic Research. 1999 February; 46(2): 103-16. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10098820&dopt=Abstract
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Non-pharmacological treatments of insomnia. Author(s): Lushington K, Lack L. Source: The Israel Journal of Psychiatry and Related Sciences. 2002; 39(1): 36-49. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12013709&dopt=Abstract
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Novel twelve-generation kindred of fatal familial insomnia from germany representing the entire spectrum of disease expression. Author(s): Harder A, Jendroska K, Kreuz F, Wirth T, Schafranka C, Karnatz N, TheallierJanko A, Dreier J, Lohan K, Emmerich D, Cervos-Navarro J, Windl O, Kretzschmar HA, Nurnberg P, Witkowski R. Source: American Journal of Medical Genetics. 1999 December 3; 87(4): 311-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10588836&dopt=Abstract
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NREM sleep EEG frequency spectral correlates of sleep complaints in primary insomnia subtypes. Author(s): Krystal AD, Edinger JD, Wohlgemuth WK, Marsh GR. Source: Sleep. 2002 September 15; 25(6): 630-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12224842&dopt=Abstract
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Occult sleep apnea in a recruited sample of older adults with insomnia. Author(s): Lichstein KL, Riedel BW, Lester KW, Aguillard RN. Source: Journal of Consulting and Clinical Psychology. 1999 June; 67(3): 405-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10369061&dopt=Abstract
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On the comparability of pharmacotherapy and behavior therapy for chronic insomnia. Commentary and implications. Author(s): Perlis ML, Smith MT, Cacialli DO, Nowakowski S, Orff H. Source: Journal of Psychosomatic Research. 2003 January; 54(1): 51-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12505555&dopt=Abstract
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P300 amplitude in subjects with primary insomnia is modulated by their sleep quality. Author(s): Devoto A, Violani C, Lucidi F, Lombardo C. Source: Journal of Psychosomatic Research. 2003 January; 54(1): 3-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12505550&dopt=Abstract
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Pain, anxiety and insomnia--a global perspective on the relief of suffering: comparative review. Author(s): Ghodse H. Source: The British Journal of Psychiatry; the Journal of Mental Science. 2003 July; 183: 15-21. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12835238&dopt=Abstract
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Perfectionism and chronic insomnia. Author(s): Vincent NK, Walker JR. Source: Journal of Psychosomatic Research. 2000 November; 49(5): 349-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11164059&dopt=Abstract
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Perspectives on the management of insomnia in patients with chronic respiratory disorders. Author(s): George CF. Source: Sleep. 2000 February 1; 23 Suppl 1: S31-5; Discussion S36-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10755806&dopt=Abstract
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Place of chronic insomnia in the course of depressive and anxiety disorders. Author(s): Ohayon MM, Roth T. Source: Journal of Psychiatric Research. 2003 January-February; 37(1): 9-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12482465&dopt=Abstract
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Polysomnographic evaluation of the hypnotic effect of Valeriana edulis standardized extract in patients suffering from insomnia. Author(s): Herrera-Arellano A, Luna-Villegas G, Cuevas-Uriostegui ML, Alvarez L, Vargas-Pineda G, Zamilpa-Alvarez A, Tortoriello J. Source: Planta Medica. 2001 November; 67(8): 695-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11731907&dopt=Abstract
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Practical geriatrics: insomnia in late life. Author(s): Goldstein MZ. Source: Psychiatric Services (Washington, D.C.). 2001 December; 52(12): 1573-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11726744&dopt=Abstract
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Predicting clinically significant response to cognitive behavior therapy for chronic insomnia in general medical practice: analysis of outcome data at 12 months posttreatment. Author(s): Espie CA, Inglis SJ, Harvey L. Source: Journal of Consulting and Clinical Psychology. 2001 February; 69(1): 58-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11302278&dopt=Abstract
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Predicting longer-term outcomes following psychological treatment for hypnoticdependent chronic insomnia. Author(s): Morgan K, Thompson J, Dixon S, Tomeny M, Mathers N. Source: Journal of Psychosomatic Research. 2003 January; 54(1): 21-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12505552&dopt=Abstract
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Presleep cognitions in patients with insomnia secondary to chronic pain. Author(s): Smith MT, Perlis ML, Carmody TP, Smith MS, Giles DE. Source: Journal of Behavioral Medicine. 2001 February; 24(1): 93-114. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11296472&dopt=Abstract
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Pre-sleep imagery under the microscope: a comparison of patients with insomnia and good sleepers. Author(s): Nelson J, Harvey AG. Source: Behaviour Research and Therapy. 2003 March; 41(3): 273-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12600399&dopt=Abstract
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Prevalence of insomnia and associated factors in South Korea. Author(s): Ohayon MM, Hong SC. Source: Journal of Psychosomatic Research. 2002 July; 53(1): 593-600. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12127177&dopt=Abstract
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Prevalence of insomnia in the adult Norwegian population. Author(s): Pallesen S, Nordhus IH, Nielsen GH, Havik OE, Kvale G, Johnsen BH, Skjotskift S. Source: Sleep. 2001 November 1; 24(7): 771-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11683480&dopt=Abstract
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Prevalence of insomnia in various psychiatric diagnostic categories. Author(s): Okuji Y, Matsuura M, Kawasaki N, Kometani S, Shimoyama T, Sato M, Oga K, Abe K. Source: Psychiatry and Clinical Neurosciences. 2002 June; 56(3): 239-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12047575&dopt=Abstract
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Prevalence of insomnia symptoms in patients with sleep-disordered breathing. Author(s): Krakow B, Melendrez D, Ferreira E, Clark J, Warner TD, Sisley B, Sklar D. Source: Chest. 2001 December; 120(6): 1923-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11742923&dopt=Abstract
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Prevalence, clinical characteristics, and risk factors for insomnia in the context of breast cancer. Author(s): Savard J, Simard S, Blanchet J, Ivers H, Morin CM. Source: Sleep. 2001 August 1; 24(5): 583-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11480655&dopt=Abstract
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Primary versus secondary insomnia in older adults: subjective sleep and daytime functioning. Author(s): Lichstein KL, Durrence HH, Bayen UJ, Riedel BW. Source: Psychology and Aging. 2001 June; 16(2): 264-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11405314&dopt=Abstract
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Psychological characteristics of elderly insomniacs. Author(s): Pallesen S, Nordhus IH, Kvale G, Havik OE, Nielsen GH, Johnsen BH, Skjotskift S, Hjeltnes L. Source: Scandinavian Journal of Psychology. 2002 December; 43(5): 425-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12500782&dopt=Abstract
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Psychological status and levels of sleepiness-alertness among patients with insomnia. Author(s): Rosenthal LD, Meixner RM. Source: Cns Spectr. 2003 February; 8(2): 114-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12612496&dopt=Abstract
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Psychosocial aspects of insomnia. Results of a study in general practice. Author(s): Kappler C, Hohagen F. Source: European Archives of Psychiatry and Clinical Neuroscience. 2003 February; 253(1): 49-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12664315&dopt=Abstract
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Quality of life in older adults receiving medications for anxiety, depression, or insomnia: findings from a community-based study. Author(s): Stein MB, Barrett-Connor E. Source: The American Journal of Geriatric Psychiatry : Official Journal of the American Association for Geriatric Psychiatry. 2002 September-October; 10(5): 568-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12213691&dopt=Abstract
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Quality of life in people with insomnia. Author(s): Zammit GK, Weiner J, Damato N, Sillup GP, McMillan CA. Source: Sleep. 1999 May 1; 22 Suppl 2: S379-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10394611&dopt=Abstract
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Quantitative criteria for insomnia. Author(s): Lichstein KL, Durrence HH, Taylor DJ, Bush AJ, Riedel BW. Source: Behaviour Research and Therapy. 2003 April; 41(4): 427-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12643966&dopt=Abstract
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Rapid eye movement-localized apnea in a female patient with chronic insomnia. Author(s): Kayukawa Y, Okada T, Hayakawa T, Imai M, Tomita S, Terashima M, Lan L, Ohta T. Source: Psychiatry and Clinical Neurosciences. 2002 June; 56(3): 321-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12047615&dopt=Abstract
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Re: Sadler's article regarding lamotrigine-associated insomnia in an adult tertiary care epilepsy out-patient clinic. Author(s): Nagarajan L. Source: Epilepsia. 2000 July; 41(7): 920-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10897172&dopt=Abstract
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Rebound insomnia after hypnotic withdrawal in insomniac outpatients. Author(s): Hajak G, Clarenbach P, Fischer W, Rodenbeck A, Bandelow B, Broocks A, Ruther E. Source: European Archives of Psychiatry and Clinical Neuroscience. 1998; 248(3): 148-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9728734&dopt=Abstract
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Relationship between insomnia, depression, and mortality: a 12-year follow-up of older adults in the community. Author(s): Mallon L, Broman JE, Hetta J. Source: Int Psychogeriatr. 2000 September; 12(3): 295-306. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11081951&dopt=Abstract
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Relationships between insomnia and sleep-disordered breathing. Author(s): Chung KF. Source: Chest. 2003 January; 123(1): 310-1; Author Reply 311-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12527644&dopt=Abstract
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Relaxation and sleep compression for late-life insomnia: a placebo-controlled trial. Author(s): Lichstein KL, Riedel BW, Wilson NM, Lester KW, Aguillard RN. Source: Journal of Consulting and Clinical Psychology. 2001 April; 69(2): 227-39. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11393600&dopt=Abstract
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Relaxation therapy for insomnia: nighttime and day time effects. Author(s): Means MK, Lichstein KL, Epperson MT, Johnson CT. Source: Behaviour Research and Therapy. 2000 July; 38(7): 665-78. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10875189&dopt=Abstract
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Reliability and validity of the Women's Health Initiative Insomnia Rating Scale. Author(s): Levine DW, Kripke DF, Kaplan RM, Lewis MA, Naughton MJ, Bowen DJ, Shumaker SA. Source: Psychological Assessment. 2003 June; 15(2): 137-48. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12847774&dopt=Abstract
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Reported chronic insomnia is independent of poor sleep as measured by electroencephalography. Author(s): Rosa RR, Bonnet MH. Source: Psychosomatic Medicine. 2000 July-August; 62(4): 474-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10949091&dopt=Abstract
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Risperidone for insomnia in PDDs. Author(s): Doan RJ. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 1998 December; 43(10): 1050-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9868572&dopt=Abstract
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Safety of zaleplon in the treatment of insomnia. Author(s): Israel AG, Kramer JA. Source: The Annals of Pharmacotherapy. 2002 May; 36(5): 852-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11978165&dopt=Abstract
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Scalp and body acupuncture for treatment of senile insomnia--a report of 83 cases. Author(s): Lu Z. Source: J Tradit Chin Med. 2002 September; 22(3): 193-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12400425&dopt=Abstract
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Self-reported nap behavior and polysomnography at home in midlife women with and without insomnia. Author(s): Johnston SK, Landis CA, Lentz MJ, Shaver JL. Source: Sleep. 2001 December 15; 24(8): 913-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11766161&dopt=Abstract
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Serial positron emission tomographic findings in an atypical presentation of fatal familial insomnia. Author(s): Bar KJ, Hager F, Nenadic I, Opfermann T, Brodhun M, Tauber RF, Patt S, Schulz-Schaeffer W, Gottschild D, Sauer H. Source: Archives of Neurology. 2002 November; 59(11): 1815-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12433271&dopt=Abstract
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SF-36: evaluation of quality of life in severe and mild insomniacs compared with good sleepers. Author(s): Leger D, Scheuermaier K, Philip P, Paillard M, Guilleminault C. Source: Psychosomatic Medicine. 2001 January-February; 63(1): 49-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11211064&dopt=Abstract
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Short-term training increases diagnostic and treatment rate for insomnia in general practice. Author(s): Backhaus J, Junghanns K, Mueller-Popkes K, Broocks A, Riemann D, Hajak G, Hohagen F. Source: European Archives of Psychiatry and Clinical Neuroscience. 2002 June; 252(3): 99-104. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12192465&dopt=Abstract
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Single-factor theories of insomnia--handle with care. Author(s): Morgan K. Source: Age and Ageing. 2003 March; 32(2): 123-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12615552&dopt=Abstract
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Sleep architecture and its relationship to insomnia. Author(s): Erman MK. Source: The Journal of Clinical Psychiatry. 2001; 62 Suppl 10: 9-17. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11388592&dopt=Abstract
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Sleep disorders. Obstructive sleep apnea syndrome, restless legs syndrome, and insomnia in geriatric patients. Author(s): Barthlen GM. Source: Geriatrics. 2002 November; 57(11): 34-9; Quiz 40. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12442567&dopt=Abstract
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Sleep duration, insomnia and behavioral problems among Chinese adolescents. Author(s): Liu X, Zhou H. Source: Psychiatry Research. 2002 August 5; 111(1): 75-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12140122&dopt=Abstract
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Sleep EEG power spectra, insomnia, and chronic use of benzodiazepines. Author(s): Bastien CH, LeBlanc M, Carrier J, Morin CM. Source: Sleep. 2003 May 1; 26(3): 313-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12749551&dopt=Abstract
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Sleep in the laboratory and sleep at home II: comparisons of middle-aged insomnia sufferers and normal sleepers. Author(s): Edinger JD, Glenn DM, Bastian LA, Marsh GR, Daile D, Hope TV, Young M, Shaw E, Meeks G. Source: Sleep. 2001 November 1; 24(7): 761-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11683479&dopt=Abstract
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Somatic and psychological complaints and their correlates with insomnia in the Japanese general population. Author(s): Kim K, Uchiyama M, Liu X, Shibui K, Ohida T, Ogihara R, Okawa M. Source: Psychosomatic Medicine. 2001 May-June; 63(3): 441-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11382271&dopt=Abstract
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Some basic features of the new sleep-aid tea (SAT) for the treatment of insomnia. Author(s): Shiyi L. Source: Sleep Res Online. 2000; 3(2): 49-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11382900&dopt=Abstract
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Strategies for evaluating adherence to sleep restriction treatment for insomnia. Author(s): Riedel BW, Lichstein KL. Source: Behaviour Research and Therapy. 2001 February; 39(2): 201-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11153973&dopt=Abstract
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Strategies to overcome insomnia. Author(s): Thobaben M. Source: Home Care Provider. 2001 April; 6(2): 46-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11295680&dopt=Abstract
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Stress exposure, psychological distress, and physiological stress activation in midlife women with insomnia. Author(s): Shaver JL, Johnston SK, Lentz MJ, Landis CA. Source: Psychosomatic Medicine. 2002 September-October; 64(5): 793-802. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12271110&dopt=Abstract
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Substance use for insomnia in Metropolitan Detroit. Author(s): Roehrs T, Hollebeek E, Drake C, Roth T. Source: Journal of Psychosomatic Research. 2002 July; 53(1): 571-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12127173&dopt=Abstract
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Subtyping primary insomnia: is sleep state misperception a distinct clinical entity? Author(s): Edinger JD, Krystal AD. Source: Sleep Medicine Reviews. 2003 June; 7(3): 203-14. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12927120&dopt=Abstract
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Symptom reports in severe chronic insomnia. Author(s): Moul DE, Nofzinger EA, Pilkonis PA, Houck PR, Miewald JM, Buysse DJ. Source: Sleep. 2002 August 1; 25(5): 553-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12150322&dopt=Abstract
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Temporal and stagewise distribution of high frequency EEG activity in patients with primary and secondary insomnia and in good sleeper controls. Author(s): Perlis ML, Kehr EL, Smith MT, Andrews PJ, Orff H, Giles DE. Source: Journal of Sleep Research. 2001 June; 10(2): 93-104. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11422723&dopt=Abstract
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Tenses of insomnia epidemiology. Author(s): Ohayon MM, Shapiro CM. Source: Journal of Psychosomatic Research. 2002 July; 53(1): 525-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12127167&dopt=Abstract
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Test-retest reliability and validity of the Pittsburgh Sleep Quality Index in primary insomnia. Author(s): Backhaus J, Junghanns K, Broocks A, Riemann D, Hohagen F. Source: Journal of Psychosomatic Research. 2002 September; 53(3): 737-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12217446&dopt=Abstract
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The clinical effectiveness of cognitive behaviour therapy for chronic insomnia: implementation and evaluation of a sleep clinic in general medical practice. Author(s): Espie CA, Inglis SJ, Tessier S, Harvey L. Source: Behaviour Research and Therapy. 2001 January; 39(1): 45-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11125723&dopt=Abstract
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The diagnosis of primary insomnia and treatment alternatives. Author(s): Perlis ML, Youngstedt SD. Source: Compr Ther. 2000 Winter; 26(4): 298-306. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11126102&dopt=Abstract
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The differential functions of imagery and verbal thought in insomnia. Author(s): Nelson J, Harvey AG. Source: Journal of Abnormal Psychology. 2002 November; 111(4): 665-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12428780&dopt=Abstract
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The insomnia plague: a Gabriel Garcia Marquez story. Author(s): Sghirlanzoni A, Carella F. Source: Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2000 August; 21(4): 251-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11214666&dopt=Abstract
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The key-lock principle in the diagnosis and treatment of nonorganic insomnia related to psychiatric disorders: sleep laboratory investigations. Author(s): Saletu-Zyhlarz GM, Arnold O, Saletu B, Anderer P. Source: Methods Find Exp Clin Pharmacol. 2002; 24 Suppl D: 37-49. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12575467&dopt=Abstract
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The long-term effects of auricular therapy using magnetic pearls on elderly with insomnia. Author(s): Suen LK, Wong TK, Leung AW, Ip WC. Source: Complementary Therapies in Medicine. 2003 June; 11(2): 85-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12801493&dopt=Abstract
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The relationship between psychiatric diseases and insomnia. Author(s): Roth T. Source: Int J Clin Pract Suppl. 2001 January; (116): 3-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11219330&dopt=Abstract
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The role of benzodiazepines in the treatment of insomnia: meta-analysis of benzodiazepine use in the treatment of insomnia. Author(s): Holbrook A, Crowther R, Lotter A, Endeshaw Y. Source: Journal of the American Geriatrics Society. 2001 June; 49(6): 824-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11454123&dopt=Abstract
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The use of actigraphy revised: the value for clinical practice in insomnia. Author(s): Verbeek I, Klip EC, Declerck AC. Source: Percept Mot Skills. 2001 June; 92(3 Pt 1): 852-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11453214&dopt=Abstract
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To breathe, perchance to sleep: sleep-disordered breathing and chronic insomnia among trauma survivors. Author(s): Krakow B, Melendrez D, Warner TD, Dorin R, Harper R, Hollifield M. Source: Sleep & Breathing = Schlaf & Atmung. 2002 December; 6(4): 189-202. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12524572&dopt=Abstract
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Trait anxiety and sleep-onset insomnia: evaluation of treatment using anxiety management training. Author(s): Viens M, De Koninck J, Mercier P, St-Onge M, Lorrain D. Source: Journal of Psychosomatic Research. 2003 January; 54(1): 31-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12505553&dopt=Abstract
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Treatment for insomnia. Author(s): Finucane TE. Source: Lancet. 2002 April 20; 359(9315): 1434; Author Reply 1434. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11978363&dopt=Abstract
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Treatment of insomnia with zaleplon, a novel sleep medication. Author(s): Doghramji PP. Source: Int J Clin Pract. 2001 June; 55(5): 329-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11452683&dopt=Abstract
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Treatment of phlegm- and heat-induced insomnia by acupuncture in 120 cases. Author(s): Cui R, Zhou D. Source: J Tradit Chin Med. 2003 March; 23(1): 57-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12747205&dopt=Abstract
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Treatment of primary insomnia with melatonin: a double-blind, placebo-controlled, crossover study. Author(s): Almeida Montes LG, Ontiveros Uribe MP, Cortes Sotres J, Heinze Martin G. Source: Journal of Psychiatry & Neuroscience : Jpn. 2003 May; 28(3): 191-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12790159&dopt=Abstract
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Treatment preference and patient satisfaction in chronic insomnia. Author(s): Vincent N, Lionberg C. Source: Sleep. 2001 June 15; 24(4): 411-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11403525&dopt=Abstract
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Trimipramine in primary insomnia: results of a polysomnographic double-blind controlled study. Author(s): Riemann D, Voderholzer U, Cohrs S, Rodenbeck A, Hajak G, Ruther E, Wiegand MH, Laakmann G, Baghai T, Fischer W, Hoffmann M, Hohagen F, Mayer G, Berger M. Source: Pharmacopsychiatry. 2002 September; 35(5): 165-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12237787&dopt=Abstract
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Ultrastructural pathology of Creutzfeldt-Jakob disease and fatal familial insomnia. Author(s): Liberski PP, Giraud P, Kopp N. Source: Folia Neuropathol. 2000; 38(4): 171-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11693721&dopt=Abstract
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Understanding insomnia and its management. Author(s): Ariff KM. Source: Med J Malaysia. 2001 September; 56(3): 386-94. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11732089&dopt=Abstract
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Upper airway resistance syndrome, insomnia, and functional somatic syndromes. Author(s): Guilleminault C, Dave R. Source: Chest. 2003 January; 123(1): 12-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12527594&dopt=Abstract
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Use of sleep hygiene in the treatment of insomnia. Author(s): Stepanski EJ, Wyatt JK. Source: Sleep Medicine Reviews. 2003 June; 7(3): 215-25. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12927121&dopt=Abstract
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What are the benefits and risks associated with the use of benzodiazepines to treat insomnia? Author(s): Lord RW Jr. Source: The Journal of Family Practice. 2000 May; 49(5): 468-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10836784&dopt=Abstract
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What are the contributing factors for insomnia in the general population? Author(s): Ohayon MM, Roth T. Source: Journal of Psychosomatic Research. 2001 December; 51(6): 745-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11750297&dopt=Abstract
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Zaleplon - a review of a novel sedative hypnotic used in the treatment of insomnia. Author(s): Heydorn WE. Source: Expert Opinion on Investigational Drugs. 2000 April; 9(4): 841-58. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11060714&dopt=Abstract
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Zaleplon improves sleep without producing rebound effects in outpatients with insomnia. Zaleplon Clinical Study Group. Author(s): Fry J, Scharf M, Mangano R, Fujimori M. Source: International Clinical Psychopharmacology. 2000 May; 15(3): 141-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10870872&dopt=Abstract
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Zaleplon shortens subjective sleep latency and improves subjective sleep quality in elderly patients with insomnia. The Zaleplon Clinical Investigator Study Group. Author(s): Hedner J, Yaeche R, Emilien G, Farr I, Salinas E. Source: International Journal of Geriatric Psychiatry. 2000 August; 15(8): 704-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10960882&dopt=Abstract
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Zaleplon: a review of its use in the treatment of insomnia. Author(s): Dooley M, Plosker GL. Source: Drugs. 2000 August; 60(2): 413-45. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10983740&dopt=Abstract
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Zolpidem “as needed” for the treatment of primary insomnia: a double-blind, placebo-controlled study. Author(s): Walsh JK. Source: Sleep Medicine Reviews. 2002 October; 6 Suppl 1: S7-10; Discussion S10-1, S31-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12607571&dopt=Abstract
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Zolpidem for insomnia related to PTSD. Author(s): Dieperink ME, Drogemuller L. Source: Psychiatric Services (Washington, D.C.). 1999 March; 50(3): 421. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10096658&dopt=Abstract
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Zolpidem for persistent insomnia in SSRI-treated depressed patients. Author(s): Asnis GM, Chakraburtty A, DuBoff EA, Krystal A, Londborg PD, Rosenberg R, Roth-Schechter B, Scharf MB, Walsh JK. Source: The Journal of Clinical Psychiatry. 1999 October; 60(10): 668-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10549683&dopt=Abstract
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Zolpidem, a valuable alternative to benzodiazepine hypnotics for chronic insomnia? Author(s): Declerck A, Smits M. Source: J Int Med Res. 1999; 27(6): 253-63. Erratum In: J Int Med Res 2000; 28(1): 46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10726234&dopt=Abstract
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Zolpidem: an update of its pharmacology, therapeutic efficacy and tolerability in the treatment of insomnia. Author(s): Holm KJ, Goa KL. Source: Drugs. 2000 April; 59(4): 865-89. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10804040&dopt=Abstract
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Zopiclone and zaleplon vs benzodiazepines in the treatment of insomnia: Canadian consensus statement. Author(s): Montplaisir J, Hawa R, Moller H, Morin C, Fortin M, Matte J, Reinish L, Shapiro CM. Source: Human Psychopharmacology. 2003 January; 18(1): 29-38. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12532313&dopt=Abstract
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CHAPTER 2. NUTRITION AND INSOMNIA Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and insomnia.
Finding Nutrition Studies on Insomnia The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements; National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: 301-435-2920, Fax: 301-480-1845, E-mail:
[email protected]). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.7 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “insomnia” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.
7 Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.
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The following information is typical of that found when using the “Full IBIDS Database” to search for “insomnia” (or a synonym): •
“As needed” pharmacotherapy combined with stimulus control treatment in chronic insomnia--assessment of a novel intervention strategy in a primary care setting. Author(s): Department of Psychiatry and Psychotherapy, University of Regensburg, Germany.
[email protected] Source: Hajak, G Bandelow, B Zulley, J Pittrow, D Ann-Clin-Psychiatry. 2002 March; 14(1): 1-7 1040-1237
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46 cases of insomnia treated by semiconductor laser irradiation on auricular points. Author(s): Institute of Acupuncture and Moxibustion, China Academy of Traditional Chinese Medicine, Beijing. Source: Yao, S J-Tradit-Chin-Med. 1999 December; 19(4): 298-9 0254-6272
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Acupuncture treatment for insomnia and acupuncture analgesia. Author(s): Department of Physiology, Shanghai Second Medical University, China. Source: Lin, Y Psychiatry-Clin-Neurosci. 1995 May; 49(2): 119-20 1323-1316
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Anxiety, depression, and insomnia. Author(s): Department of Family Medicine, Louisiana State University Health Sciences Center, School of Medicine, 200 West Esplanade Avenue, Suite 510, Kenner, LA 70065, USA.
[email protected] Source: Larzelere, M M Wiseman, P Prim-Care. 2002 June; 29(2): 339-60, vii 0095-4543
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Beta-CIT SPECT demonstrates reduced availability of serotonin transporters in patients with Fatal Familial Insomnia. Author(s): Institute of Neurology, University of Vienna, Wahringer Gurtel 18-20, A-1090 Vienna, Austria. Source: Kloppel, S Pirker, W Brucke, T Kovacs, G G Almer, G J-Neural-Transm. 2002 July; 109(7-8): 1105-10 0300-9564
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Beyond benzodiazepines: alternative pharmacologic agents for the treatment of insomnia. Author(s): College of Pharmacy, Rutgers State University of New Jersey, Piscataway 08854, USA. Source: Wagner, J Wagner, M L Hening, W A Ann-Pharmacother. 1998 June; 32(6): 68091 1060-0280
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Caffeine use as a model of acute and chronic insomnia. Author(s): Dayton Veterans Administration Medical Center, Ohio. Source: Bonnet, M H Arand, D L Sleepage 1992 December; 15(6): 526-36 0161-8105
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Can valerian improve the sleep of insomniacs after benzodiazepine withdrawal? Author(s): Sleep Laboratory of the Department of Psychobiology, Universidade Federal de Sao Paulo, Sao Paulo, Brazil. Source: Poyares, D R Guilleminault, C Ohayon, M M Tufik, S ProgNeuropsychopharmacol-Biol-Psychiatry. 2002 April; 26(3): 539-45 0278-5846
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Clinical observation of 62 cases of insomnia treated by auricular point imbedding therapy. Source: Yang, C L J-Tradit-Chin-Med. 1988 September; 8(3): 190-2 0254-6272
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Continuous versus non-nightly use of zolpidem in chronic insomnia: results of a large-scale, double-blind, randomized, outpatient study. Author(s): Department of Psychiatry and Psychotherapy, University of Regensburg, Germany.
[email protected] Nutrition
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Source: Hajak, G Cluydts, R Declerck, A Estivill, S Eduard Middleton, A Sonka, K Unden, M Int-Clin-Psychopharmacol. 2002 January; 17(1): 9-17 0268-1315 •
Effect of a fixed valerian-Hop extract combination (Ze 91019) on sleep polygraphy in patients with non-organic insomnia: a pilot study. Author(s): Zeller AG, Seeblickstr. 4, CH-8590 Romanshorn, Switzerland. axel.
[email protected] Source: Fussel, A Wolf, A Brattstrom, A Eur-J-Med-Res. 2000 September 18; 5(9): 385-90 0949-2321
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Evidence based complementary intervention for insomnia. Author(s): National Center for PTSD, Department of Veterans Affairs, Spark M. Matsunaga Medical and Regional Office Center, 1132 Bishop St., Suite 307, Honolulu, HI 96813, USA. Source: Lopez, H H Bracha, A S Bracha, H S Hawaii-Med-J. 2002 September; 61(9): 192, 213 0017-8594
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Experience in differentiation and treatment of stubborn insomnia. Author(s): General Hospital of PLA Navy, 6 Fucheng Street, Haidian District, Beijing 100037. Source: Qian, Y J-Tradit-Chin-Med. 2001 September; 21(3): 168-73 0254-6272
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Herbal treatment of insomnia. Author(s): Department of Psychiatry, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong. Source: Wing, Y K Hong-Kong-Med-J. 2001 December; 7(4): 392-402 1024-2708
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Impulse magnetic-field therapy for insomnia: a double-blind, placebo-controlled study. Author(s): Universitat der Bundeswehr Munchen Neubiberg/Munich, Germany. Source: Pelka, R B Jaenicke, C Gruenwald, J Adv-Ther. 2001 Jul-August; 18(4): 174-80 0741-238X
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Insomnia in depression: differences in objective and subjective sleep and awakening quality to normal controls and acute effects of trazodone. Author(s): Department of Psychiatry, University of Vienna, Austria. Source: Saletu Zyhlarz, Gerda Maria Abu Bakr, Manal Hassan Anderer, Peter Gruber, Georg Mandl, Magdalena Strobl, Roland Gollner, Dietmar Prause, Wolfgang Saletu, Bernd Prog-Neuropsychopharmacol-Biol-Psychiatry. 2002 February; 26(2): 249-60 02785846
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Insomnia treated by auricular pressing therapy. Author(s): Department of TCM, General PLA Hospital of Chengdu Military Region. Source: Lian, N Yan, Q J-Tradit-Chin-Med. 1990 September; 10(3): 174-5 0254-6272
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Insomnia. Get a good night's sleep. Source: Anonymous Harv-Health-Lett. 1998 December; 24(2): 1-3 1052-1577
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Is possible to correct insomnia in an infant due to nutrition by a modification of the nutrition regime. Peut-on corriger l'insomnie du nourrisson et du jeune enfant par une modification du regime alimentaire. Source: Kahn, M.M.J. Rebuffat, A. Casimir, E. Duchateau, G. Sottiaux M, J. Proceedings of the Xth International Congress of Dietetics / held under the auspices of the I.C.D.A. (the International Committee of Dietetic Associations); edited by M.F. Moyal. London : Libbey Eurotext, c1988. volume 1 page 181-192.
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Kava and valerian in the treatment of stress-induced insomnia. Source: Wheatley, D. PTR,-Phytother-res. West Sussex : John Wiley & Sons Ltd. Sept 2001. volume 15 (6) page 549-551. 0951-418X
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Lectures on formulating acupuncture prescriptions--selection and matching of acupoints. Acupuncture treatment of insomnia. Source: Zhao, C X J-Tradit-Chin-Med. 1987 June; 7(2): 151-2 0254-6272
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Magnesium therapy for periodic leg movements-related insomnia and restless legs syndrome: an open pilot study. Author(s): Department of Psychiatry and Psychotherapy, Albert-Ludwigs-University, Freiburg, Germany. Source: Hornyak, M Voderholzer, U Hohagen, F Berger, M Riemann, D Sleepage 1998 August 1; 21(5): 501-5 0161-8105
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Melatonin add-on in manic patients with treatment resistant insomnia. Author(s): Department of Psychiatric Science and Psychological Medicine, University of Rome La Sapienza, Italy.
[email protected] Source: Bersani, G Garavini, A Prog-Neuropsychopharmacol-Biol-Psychiatry. 2000 February; 24(2): 185-91 0278-5846
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Melatonin and insomnia. Author(s): University Department of Neurology, King's College School of Medicine and Dentistry, London, UK. Source: Ellis, C M Lemmens, G Parkes, J D J-Sleep-Res. 1996 March; 5(1): 61-5 0962-1105
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Melatonin as a chronobiotic for circadian insomnia. Clinical observations and animal models. Author(s): Brain Sciences Institute, Swinburne University of Technology, Hawthorn, Victoria, Australia. Source: Armstrong, S M Adv-Exp-Med-Biol. 1999; 460283-97 0065-2598
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Melatonin in elderly patients with insomnia. A systematic review. Author(s): Dept. Geriatric Medicine, University Hospital Nijmegen, Code 318, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
[email protected] Source: Olde Rikkert, M G Rigaud, A S Z-Gerontol-Geriatr. 2001 December; 34(6): 491-7 0948-6704
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Melatonin treatment for age-related insomnia. Author(s): Department of Brain and Cognitive Sciences, Clinical Research Center, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA. Source: Zhdanova, I V Wurtman, R J Regan, M M Taylor, J A Shi, J P Leclair, O U J-ClinEndocrinol-Metab. 2001 October; 86(10): 4727-30 0021-972X
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Polysomnographic Evaluation of the Hypnotic Effect of Valeriana edulis Standardized Extract in Patients Suffering from Insomnia. Author(s): Centro de Investigacion Biomedica del Sur, IMSS., Morelos, Mexico. Source: Herrera Arellano, A Luna Villegas, G Cuevas Uriostegui, M L Alvarez, L Vargas Pineda, G Zamilpa Alvarez, A Tortoriello, J Planta-Med. 2001 November; 67(8): 695-9 0032-0943
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Prof. Kong Lingxu's experience in TCM treatment of insomnia. Author(s): Institute of TCM Basic Theories, China Academy of Traditional Chinese Medicine, Beijing. Source: Peng, J J-Tradit-Chin-Med. 1999 September; 19(3): 175-81 0254-6272
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Reversibility of para-chlorophenylalanine-induced insomnia by intrahypothalamic microinjection of L-5-hydroxytryptophan. Author(s): Departement de Medecine Experimentale, INSERM U52, CNRS UA1195, Faculte de Medecine, Universite Claude Bernard, Lyon, France. Source: Denoyer, M Sallanon, M Kitahama, K Aubert, C Jouvet, M Neuroscience. 1989; 28(1): 83-94 0306-4522
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Scalp and body acupuncture for treatment of senile insomnia--a report of 83 cases. Author(s): Fuyang Municipal Rehabilitation Hospital, Fuyang 236000, Anhui Province. Source: Lu, Z J-Tradit-Chin-Med. 2002 September; 22(3): 193-4 0254-6272
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Sleep disorders in Chinese culture: experiences from a study of insomnia in Taiwan. Author(s): Department of Psychiatry, School of Medicine, National Taiwan University, Taipei, Taiwan. Source: Lee, Y J Psychiatry-Clin-Neurosci. 1995 May; 49(2): 103-6 1323-1316
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Some basic features of the new sleep-aid tea (SAT) for the treatment of insomnia. Author(s): Shanghai Institute of Physiology, Academia Sinica Shanghai Huake Institute of Sleep and Anti-dementia (SHISA) Shanghai, China. Source: Shiyi, L Sleep-Res-Online. 2000; 3(2): 49-52 1096-214X
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The role of melatonin and circadian phase in age-related sleep-maintenance insomnia: assessment in a clinical trial of melatonin replacement. Author(s): Department of Psychiatry, School of Medicine, Oregon Health Sciences University, Portland, USA. Source: Hughes, R J Sack, R L Lewy, A J Sleepage 1998; 21(1): 52-68 0161-8105
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The therapeutic effect of mulberry in the treatment of constipation and insomnia in the elderly. Source: Weng, M H Chen, Z J-Tradit-Chin-Med. 1989 June; 9(2): 93-4 0254-6272
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The tryptophan depletion test: impact on sleep in primary insomnia - a pilot study. Author(s): Department of Psychiatry and Psychotherapy, University of Freiburg, Hauptstrasse 5, Germany.
[email protected] Source: Riemann, Dieter Feige, Bernd Hornyak, Magdolna Koch, Stephanie Hohagen, Fritz Voderholzer, Ulrich Psychiatry-Res. 2002 March 15; 109(2): 129-35 0165-1781
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The use of melatonin for the treatment of insomnia. Author(s): Department of Neurobiochemistry, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
[email protected] Source: Zisapel, N Biol-Signals-Recept. 1999 Jan-April; 8(1-2): 84-9 1422-4933
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Therapy of insomnia. Author(s): Division of Pulmonary, Sleep and Critical Care Medicine, Rhode Island Hospital, 593 Eddy Street, Providence, Rhode Island 02903, USA.
[email protected] Source: Millman, Richard P Med-Health-R-I. 2002 March; 85(3): 99-100 1086-5462
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Treatment of insomnia: an alternative approach. Author(s): Department of Anesthesia & Critical Care, The Pritzker School of Medicine, the University of Chicago, Chicago, IL, USA. Source: Attele, A S Xie, J T Yuan, C S Altern-Med-Revolume 2000 June; 5(3): 249-59 10895159
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Treatment of severe chronic insomnia with L-tryptophan and varying sleeping times. Author(s): Department of Psychiatry, Hospital of the University Frankfurt/M., FRG.
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Source: Demisch, K Bauer, J Georgi, K Pharmacopsychiatry. 1987 November; 20(6): 245-8 0176-3679
Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •
healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0
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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov
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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov
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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/
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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/
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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/
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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/
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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/
Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html
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Google: http://directory.google.com/Top/Health/Nutrition/
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Healthnotes: http://www.healthnotes.com/
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Open Directory Project: http://dmoz.org/Health/Nutrition/
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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/
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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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The following is a specific Web list relating to insomnia; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •
Vitamins Niacin Source: Integrative Medicine Communications; www.drkoop.com Vitamin B Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10067,00.html Vitamin B12 Source: Healthnotes, Inc.; www.healthnotes.com Vitamin B3 (niacin) Source: Integrative Medicine Communications; www.drkoop.com Vitamin C Source: Prima Communications, Inc.www.personalhealthzone.com Vitamin D Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,905,00.html
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Minerals Calcium Source: Integrative Medicine Communications; www.drkoop.com Calcium Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,884,00.html Calcium/magnesium Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,937,00.html Clorazepate Dipotassium Source: Healthnotes, Inc.; www.healthnotes.com Magnesium Source: Healthnotes, Inc.; www.healthnotes.com Magnesium Source: Integrative Medicine Communications; www.drkoop.com
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Food and Diet Chocolate Source: Healthnotes, Inc.; www.healthnotes.com Coffee Source: Healthnotes, Inc.; www.healthnotes.com Garlic Source: Prima Communications, Inc.www.personalhealthzone.com Oats Alternative names: Avena sativa Source: Healthnotes, Inc.; www.healthnotes.com Tea Source: Healthnotes, Inc.; www.healthnotes.com Yogurt Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,97,00.html
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CHAPTER 3. ALTERNATIVE MEDICINE AND INSOMNIA Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to insomnia. 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 insomnia 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 “insomnia” (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 insomnia: •
“Brain music” in the treatment of patients with insomnia. Author(s): Levin YaI. Source: Neuroscience and Behavioral Physiology. 1998 May-June; 28(3): 330-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9682240&dopt=Abstract
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46 cases of insomnia treated by semiconductor laser irradiation on auricular points. Author(s): Yao S. Source: J Tradit Chin Med. 1999 December; 19(4): 298-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10921138&dopt=Abstract
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86 cases of insomnia treated by double point needling--daling through to waiguan. Author(s): Ren Y.
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Source: J Tradit Chin Med. 1985 March; 5(1): 22. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3849624&dopt=Abstract •
A behavioral perspective on insomnia treatment. Author(s): Spielman AJ, Caruso LS, Glovinsky PB. Source: The Psychiatric Clinics of North America. 1987 December; 10(4): 541-53. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3332317&dopt=Abstract
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A breathing-retraining procedure in treatment of sleep-onset insomnia: theoretical basis and experimental findings. Author(s): Choliz M. Source: Percept Mot Skills. 1995 April; 80(2): 507-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7675582&dopt=Abstract
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A cognitive-behavioral therapy for sleep-maintenance insomnia in older adults. Author(s): Edinger JD, Hoelscher TJ, Marsh GR, Lipper S, Ionescu-Pioggia M. Source: Psychology and Aging. 1992 June; 7(2): 282-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1610517&dopt=Abstract
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A comparison of relaxation techniques with electrosleep therapy for chronic, sleeponset insomnia a sleep-EEG study. Author(s): Coursey RD, Frankel BL, Gaarder KR, Mott DE. Source: Biofeedback Self Regul. 1980 March; 5(1): 57-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6989409&dopt=Abstract
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A preliminary study comparing sleep restriction and relaxation treatments for insomnia in older adults. Author(s): Friedman L, Bliwise DL, Yesavage JA, Salom SR. Source: J Gerontol. 1991 January; 46(1): P1-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1986039&dopt=Abstract
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A wake-up call for caution. If insomnia is the patient's problem, is over-the-counter melatonin the cure? Author(s): Butler RN. Source: Geriatrics. 1996 February; 51(2): 14, 16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8631528&dopt=Abstract
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Active and placebo effects in treatment of moderate and severe insomnia. Author(s): Carr-Kaffashan L, Woolfolk RL. Source: Journal of Consulting and Clinical Psychology. 1979 December; 47(6): 1072-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=41856&dopt=Abstract
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Acupuncture treatment for insomnia and acupuncture analgesia. Author(s): Lin Y. Source: Psychiatry and Clinical Neurosciences. 1995 May; 49(2): 119-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8726127&dopt=Abstract
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Acupuncture treatment of insomnia--a report of 28 cases. Author(s): Shi D. Source: J Tradit Chin Med. 2003 June; 23(2): 136-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12875082&dopt=Abstract
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An evaluation of behavioral treatments for insomnia in the older adult. Author(s): Engle-Friedman M, Bootzin RR, Hazlewood L, Tsao C. Source: Journal of Clinical Psychology. 1992 January; 48(1): 77-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1556221&dopt=Abstract
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An evaluation of tailored psychological treatment of insomnia. Author(s): Espie CA, Brooks DN, Lindsay WR. Source: Journal of Behavior Therapy and Experimental Psychiatry. 1989 June; 20(2): 14353. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2685045&dopt=Abstract
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An hypnotic technique for treating insomnia. Author(s): Bauer KE, McCanne TR. Source: Int J Clin Exp Hypn. 1980 January; 28(1): 1-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7353922&dopt=Abstract
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An open-label trial of evidence-based cognitive behavior therapy for nightmares and insomnia in crime victims with PTSD. Author(s): Krakow B, Johnston L, Melendrez D, Hollifield M, Warner TD, ChavezKennedy D, Herlan MJ. Source: The American Journal of Psychiatry. 2001 December; 158(12): 2043-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11729023&dopt=Abstract
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An untenable rationale for treating insomnia. Author(s): van den Hout M, Kroeze S. Source: Percept Mot Skills. 1995 August; 81(1): 316-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8532474&dopt=Abstract
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Anxiety, depression, and insomnia. Author(s): Larzelere MM, Wiseman P.
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Source: Primary Care. 2002 June; 29(2): 339-60, Vii. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12391715&dopt=Abstract •
Behavioral self-management in treating sleep-maintenance insomnia. Author(s): Thoresen CE, Coates TJ, Kirmil-Gray K, Rosekind MR. Source: Journal of Behavioral Medicine. 1981 March; 4(1): 41-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7026793&dopt=Abstract
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Behavioral treatment for chronic insomnia. Author(s): Arnedt JT, Martin JL, Posner DA. Source: Medicine and Health, Rhode Island. 2002 March; 85(3): 90-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11917751&dopt=Abstract
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Behavioral treatment of chronic insomnia in psychiatrically ill patients. Author(s): Dashevsky BA, Kramer M. Source: The Journal of Clinical Psychiatry. 1998 December; 59(12): 693-9; Quiz 700-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9921709&dopt=Abstract
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Behavioral treatment of insomnia in older adults: an open clinical trial comparing two interventions. Author(s): Pallesen S, Nordhus IH, Kvale G, Nielsen GH, Havik OE, Johnsen BH, Skjotskift S. Source: Behaviour Research and Therapy. 2003 January; 41(1): 31-48. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12488118&dopt=Abstract
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Behavioral treatment of insomnia: the Wilford Hall Insomnia Program. Author(s): Hryshko-Mullen AS. Source: Military Medicine. 2000 March; 165(3): 200-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10741083&dopt=Abstract
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Best bets for managing insomnia: drug therapy, behavioral interventions. Author(s): Rollins G. Source: Rep Med Guidel Outcomes Res. 2001 April 5; 12(7): 10, 12. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12075628&dopt=Abstract
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Comparative studies on the effects of the combination drug lorazepam plus diphenhydramine (Somnium) versus lorazepam on the noopsyche, thymopsyche and psychophysiology in nonorganic insomnia related to generalized anxiety disorder. Author(s): Grunberger J, Saletu B, Linzmayer L, Bock G, Weissgram S, Brandstaatter N, Frey R, Saletu-Zyhlarz G. Source: Methods Find Exp Clin Pharmacol. 1997 November; 19(9): 645-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9500129&dopt=Abstract
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Controlled comparison of progressive relaxation, stimulus control, and paradoxical intention therapies for insomnia. Author(s): Turner RM, Ascher LM.
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Effects of metronome-conditioned relaxation, metronome-induced relaxation, and progressive muscle relaxation on insomnia. Author(s): Pendleton LR, Tasto DL. Source: Behaviour Research and Therapy. 1976; 14(2): 165-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=779760&dopt=Abstract
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Effects of passive body heating on the sleep of older female insomniacs. Author(s): Dorsey CM, Lukas SE, Teicher MH, Harper D, Winkelman JW, Cunningham SL, Satlin A.
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Efficacy and tolerability of valerian extract LI 156 compared with oxazepam in the treatment of non-organic insomnia--a randomized, double-blind, comparative clinical study. Author(s): Ziegler G, Ploch M, Miettinen-Baumann A, Collet W. Source: European Journal of Medical Research. 2002 November 25; 7(11): 480-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12568976&dopt=Abstract
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Efficiency of transcranial electrostimulation on anxiety and insomnia symptoms during a washout period in depressed patients. A double-blind study. Author(s): Philip P, Demotes-Mainard J, Bourgeois M, Vincent JD. Source: Biological Psychiatry. 1991 March 1; 29(5): 451-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2018818&dopt=Abstract
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Evaluation and management of insomnia in menopause. Author(s): Jones CR, Czajkowski L. Source: Clinical Obstetrics and Gynecology. 2000 March; 43(1): 184-97. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10694999&dopt=Abstract
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Evaluation of short-term nonpharmacological treatment of insomnia in a clinical setting. Author(s): Verbeek I, Schreuder K, Declerck G. Source: Journal of Psychosomatic Research. 1999 October; 47(4): 369-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10616231&dopt=Abstract
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Evidence based complementary intervention for insomnia. Author(s): Lopez HH, Bracha AS, Bracha HS. Source: Hawaii Med J. 2002 September; 61(9): 192, 213. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12422383&dopt=Abstract
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Hospitalized patients' preference in the treatment of insomnia: pharmacological versus non-pharmacological. Author(s): Azad N, Byszewski A, Sarazin FF, McLean W, Koziarz P. Source: Can J Clin Pharmacol. 2003 Summer; 10(2): 89-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12879147&dopt=Abstract
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How useful is cognitive behavioral therapy (CBT) for the treatment of chronic insomnia? Author(s): Phillips TG, Holdsworth J, Cook S. Source: The Journal of Family Practice. 2001 July; 50(7): 569. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11485698&dopt=Abstract
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Immunity and depression: insomnia, retardation, and reduction of natural killer cell activity. Author(s): Cover H, Irwin M.
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Insomnia and the attack on barbiturates. Author(s): Humphries SV. Source: Cent Afr J Med. 1978 January; 24(1): 13-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=346229&dopt=Abstract
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Melatonin for insomnia and jet lag. Author(s): Turow V. Source: Pediatrics. 1996 March; 97(3): 439. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8604288&dopt=Abstract
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Multifactor behavioral treatment of chronic sleep-onset insomnia using stimulus control and the relaxation response. A preliminary study. Author(s): Jacobs GD, Rosenberg PA, Friedman R, Matheson J, Peavy GM, Domar AD, Benson H. Source: Behavior Modification. 1993 October; 17(4): 498-509. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8216184&dopt=Abstract
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Polysomnographic evaluation of the hypnotic effect of Valeriana edulis standardized extract in patients suffering from insomnia. Author(s): Herrera-Arellano A, Luna-Villegas G, Cuevas-Uriostegui ML, Alvarez L, Vargas-Pineda G, Zamilpa-Alvarez A, Tortoriello J. Source: Planta Medica. 2001 November; 67(8): 695-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11731907&dopt=Abstract
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Prof. Kong Lingxu's experience in TCM treatment of insomnia. Author(s): Peng J. Source: J Tradit Chin Med. 1999 September; 19(3): 175-81. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10921145&dopt=Abstract
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Progressive relaxation, EMG biofeedback and biofeedback placebo in the treatment of sleep-onset insomnia. Author(s): Nicassio PM, Boylan MB, McCabe TG. Source: The British Journal of Medical Psychology. 1982 June; 55(Pt 2): 159-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7104246&dopt=Abstract
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Psychological treatment of secondary insomnia. Author(s): Lichstein KL, Wilson NM, Johnson CT. Source: Psychology and Aging. 2000 June; 15(2): 232-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10879578&dopt=Abstract
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Psychophysiological insomnia: combined effects of pharmacotherapy and relaxationbased treatments. Author(s): Rosen RC, Lewin DS, Goldberg L, Woolfolk RL. Source: Sleep Medicine. 2000 October 1; 1(4): 279-288. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11040460&dopt=Abstract
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Relaxation and hypnosis in the treatment of insomnia. Author(s): Graham KR, Wright GW, Toman WJ, Mark CB. Source: Am J Clin Hypn. 1975 July; 18(1): 39-42. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1163461&dopt=Abstract
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Relaxation and sleep compression for late-life insomnia: a placebo-controlled trial. Author(s): Lichstein KL, Riedel BW, Wilson NM, Lester KW, Aguillard RN. Source: Journal of Consulting and Clinical Psychology. 2001 April; 69(2): 227-39. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11393600&dopt=Abstract
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Relaxation for insomnia and hypnotic medication use in older women. Author(s): Lichstein KL, Johnson RS. Source: Psychology and Aging. 1993 March; 8(1): 103-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8461107&dopt=Abstract
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Relaxation therapy for insomnia: nighttime and day time effects. Author(s): Means MK, Lichstein KL, Epperson MT, Johnson CT. Source: Behaviour Research and Therapy. 2000 July; 38(7): 665-78. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10875189&dopt=Abstract
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Relaxation training and attention placebo in the treatment of severe insomnia. Author(s): Lick JR, Heffler D. Source: Journal of Consulting and Clinical Psychology. 1977 April; 45(2): 153-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=321491&dopt=Abstract
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Relaxation treatment for insomnia: a component analysis. Author(s): Woolfolk RL, McNulty TF. Source: Journal of Consulting and Clinical Psychology. 1983 August; 51(4): 495-503. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6352753&dopt=Abstract
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Relaxation treatment of pseudoinsomnia and idiopathic insomnia: an electroencephalographic evaluation. Author(s): Borkovec TD, Grayson JB, O'Brien GT, Weerts TC. Source: J Appl Behav Anal. 1979 Spring; 12(1): 37-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=381276&dopt=Abstract
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Replacement of drug treatment for insomnia by ambient odour. Author(s): Hardy M, Kirk-Smith MD, Stretch DD. Source: Lancet. 1995 September 9; 346(8976): 701. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7658836&dopt=Abstract
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Resolving the relationships between placebos, misattribution, and insomnia: an individual-differences perspective. Author(s): Brockner J, Swap WC. Source: Journal of Personality and Social Psychology. 1983 July; 45(1): 32-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6886968&dopt=Abstract
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Responses of psychophysiologic and subjective insomniacs to auditory stimuli during sleep: a replication and extension. Author(s): Haynes SN, Fitzgerald SG, Shute G, O'Meary M.
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Source: Journal of Abnormal Psychology. 1985 August; 94(3): 338-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4031231&dopt=Abstract •
Scalp and body acupuncture for treatment of senile insomnia--a report of 83 cases. Author(s): Lu Z. Source: J Tradit Chin Med. 2002 September; 22(3): 193-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12400425&dopt=Abstract
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Sleep and the treatment of insomnia. Author(s): Kavanagh P. Source: Aust Nurses J. 1976 May; 5(11): 20. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1048006&dopt=Abstract
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Sleep disorders in Chinese culture: experiences from a study of insomnia in Taiwan. Author(s): Lee YJ. Source: Psychiatry and Clinical Neurosciences. 1995 May; 49(2): 103-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8726123&dopt=Abstract
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Sleep disorders. Liver damage warning with insomnia remedy. Author(s): Shepherd C. Source: Bmj (Clinical Research Ed.). 1993 May 29; 306(6890): 1477. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8357398&dopt=Abstract
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Sleep restriction for the inpatient treatment of insomnia. Author(s): Morin CM, Kowatch RA, O'Shanick G. Source: Sleep. 1990 April; 13(2): 183-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2330476&dopt=Abstract
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Sleep: insomnia in the elderly. Author(s): Kearnes S. Source: Nurs Times. 1989 November 22-28; 85(47): 32-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2690021&dopt=Abstract
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Slow wave sleep deficiency insomnia: a problem in thermo-downregulation at sleep onset. Author(s): Sewitch DE. Source: Psychophysiology. 1987 March; 24(2): 200-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3602272&dopt=Abstract
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Some basic features of the new sleep-aid tea (SAT) for the treatment of insomnia. Author(s): Shiyi L.
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Source: Sleep Res Online. 2000; 3(2): 49-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11382900&dopt=Abstract •
Stress-induced insomnia treated with kava and valerian: singly and in combination. Author(s): Wheatley D. Source: Human Psychopharmacology. 2001 June; 16(4): 353-356. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12404572&dopt=Abstract
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Substituting behavioural treatment for drugs in the treatment of insomnia: an exploratory study. Author(s): Espie CA, Lindsay WR, Brooks DN. Source: Journal of Behavior Therapy and Experimental Psychiatry. 1988 March; 19(1): 51-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3292591&dopt=Abstract
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Teaching round: insomnia. Author(s): Ji XP. Source: J Tradit Chin Med. 1987 March; 7(1): 73-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3613644&dopt=Abstract
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The behavioral treatment of insomnia an alternative to drug therapy. Author(s): Ribordy SC, Denney DR. Source: Behaviour Research and Therapy. 1977; 15(1): 39-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13779&dopt=Abstract
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The diagnosis of primary insomnia and treatment alternatives. Author(s): Perlis ML, Youngstedt SD. Source: Compr Ther. 2000 Winter; 26(4): 298-306. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11126102&dopt=Abstract
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The differential functions of imagery and verbal thought in insomnia. Author(s): Nelson J, Harvey AG. Source: Journal of Abnormal Psychology. 2002 November; 111(4): 665-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12428780&dopt=Abstract
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The effectiveness of various treatment techniques on different degrees and durations of sleep-onset insomnia. Author(s): Shealy RC. Source: Behaviour Research and Therapy. 1979; 17(6): 541-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=393245&dopt=Abstract
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The etiology and management of insomnia. Author(s): Bond T, Wooten V. Source: Va Med Q. 1996 Fall; 123(4): 254-5. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8909147&dopt=Abstract
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The long-term effects of auricular therapy using magnetic pearls on elderly with insomnia. Author(s): Suen LK, Wong TK, Leung AW, Ip WC. Source: Complementary Therapies in Medicine. 2003 June; 11(2): 85-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12801493&dopt=Abstract
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The management of unwanted pre-sleep thoughts in insomnia: distraction with imagery versus general distraction. Author(s): Harvey AG, Payne S. Source: Behaviour Research and Therapy. 2002 March; 40(3): 267-77. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11863237&dopt=Abstract
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The mesograde amnesia of sleep may be attenuated in subjects with primary insomnia. Author(s): Perlis ML, Smith MT, Orff HJ, Andrews PJ, Giles DE. Source: Physiology & Behavior. 2001 September 1-15; 74(1-2): 71-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11564454&dopt=Abstract
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The power of suggestion: another examination of misattribution and insomnia. Author(s): Bootzin RR, Herman CP, Nicassio P. Source: Journal of Personality and Social Psychology. 1976 October; 34(4): 673-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=993978&dopt=Abstract
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The scared little boy with insomnia. Author(s): Joseph E. Source: Aust Fam Physician. 1984 December; 13(12): 895. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6525109&dopt=Abstract
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The therapeutic effect of mulberry in the treatment of constipation and insomnia in the elderly. Author(s): Weng MH, Chen Z. Source: J Tradit Chin Med. 1989 June; 9(2): 93-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2779283&dopt=Abstract
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The treatment of psychophysiologic insomnia with biofeedback: a replication study. Author(s): Hauri PJ, Percy L, Hellekson C, Hartmann E, Russ D.
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Source: Biofeedback Self Regul. 1982 June; 7(2): 223-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7138954&dopt=Abstract •
The use of EEG theta biofeedback in the treatment of a patient with sleep-onset insomnia. Author(s): Bell JS. Source: Biofeedback Self Regul. 1979 September; 4(3): 229-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=486589&dopt=Abstract
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The use of indirect hypnotic suggestions for insomnia arising from generalized anxiety: a case report. Author(s): Cochrane G. Source: Am J Clin Hypn. 1989 January; 31(3): 199-203. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2919574&dopt=Abstract
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Trait anxiety and sleep-onset insomnia: evaluation of treatment using anxiety management training. Author(s): Viens M, De Koninck J, Mercier P, St-Onge M, Lorrain D. Source: Journal of Psychosomatic Research. 2003 January; 54(1): 31-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12505553&dopt=Abstract
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Treating insomnia: a practical guide for managing chronic sleeplessness, circa 1975. Author(s): Regestein QR. Source: Comprehensive Psychiatry. 1976 July-August; 17(4): 517-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=786543&dopt=Abstract
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Treating insomnia: pharmacological and nonpharmacological approaches. Author(s): Bliwise DL. Source: J Psychoactive Drugs. 1991 October-December; 23(4): 335-41. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1813605&dopt=Abstract
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Treating psychophysiologic insomnia with biofeedback. Author(s): Hauri P. Source: Archives of General Psychiatry. 1981 July; 38(7): 752-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7247638&dopt=Abstract
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Treatment of insomnia in cancer patients using muscle relaxation training. Author(s): Cannici J, Malcolm R, Peek LA. Source: Journal of Behavior Therapy and Experimental Psychiatry. 1983 September; 14(3): 251-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6358270&dopt=Abstract
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Treatment of insomnia in depressed patients by hypnosis and cerebral electrotherapy. Author(s): Barabasz AF. Source: Am J Clin Hypn. 1976 October; 19(2): 120-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=790935&dopt=Abstract
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Treatment of insomnia: an alternative approach. Author(s): Attele AS, Xie JT, Yuan CS. Source: Alternative Medicine Review : a Journal of Clinical Therapeutic. 2000 June; 5(3): 249-59. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10869104&dopt=Abstract
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Treatment of phlegm- and heat-induced insomnia by acupuncture in 120 cases. Author(s): Cui R, Zhou D. Source: J Tradit Chin Med. 2003 March; 23(1): 57-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12747205&dopt=Abstract
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Treatment plans across psychologists assessing the same case of insomnia. Author(s): Fewtrell WD. Source: Psychological Reports. 1986 August; 59(1): 240-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3526378&dopt=Abstract
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Use of progressive relaxation training for chronic alcoholics with insomnia. Author(s): Greeff AP, Conradie WS. Source: Psychological Reports. 1998 April; 82(2): 407-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9621711&dopt=Abstract
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Valerian for insomnia: a systematic review of randomized clinical trials. Author(s): Stevinson C, Ernst E. Source: Sleep Medicine. 2000 April 1; 1(2): 91-99. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10767649&dopt=Abstract
Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •
Alternative Medicine Foundation, Inc.: http://www.herbmed.org/
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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats
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Chinese Medicine: http://www.newcenturynutrition.com/
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drkoop.com®: http://www.drkoop.com/InteractiveMedicine/IndexC.html
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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm
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Google: http://directory.google.com/Top/Health/Alternative/
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Healthnotes: http://www.healthnotes.com/
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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine
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Open Directory Project: http://dmoz.org/Health/Alternative/
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HealthGate: http://www.tnp.com/
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WebMD®Health: http://my.webmd.com/drugs_and_herbs
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/
The following is a specific Web list relating to insomnia; 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 Acne Source: Integrative Medicine Communications; www.drkoop.com Aids and Hiv Source: Integrative Medicine Communications; www.drkoop.com Alcohol Withdrawal Source: Healthnotes, Inc.; www.healthnotes.com Alcoholism Source: Integrative Medicine Communications; www.drkoop.com Alzheimer's Disease Source: Integrative Medicine Communications; www.drkoop.com Anorexia Nervosa Source: Integrative Medicine Communications; www.drkoop.com Anxiety Source: Healthnotes, Inc.; www.healthnotes.com Anxiety and Panic Attacks Source: Prima Communications, Inc.www.personalhealthzone.com Asthma Source: Prima Communications, Inc.www.personalhealthzone.com Attention Deficit Hyperactivity Disorder Source: Integrative Medicine Communications; www.drkoop.com
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Benign Prostatic Hyperplasia Source: Integrative Medicine Communications; www.drkoop.com Cancer Prevention (Reducing the Risk) Source: Prima Communications, Inc.www.personalhealthzone.com Chronic Fatigue Syndrome Source: Healthnotes, Inc.; www.healthnotes.com Chronic Fatigue Syndrome Source: Integrative Medicine Communications; www.drkoop.com Chronic Obstructive Pulmonary Disease Source: Healthnotes, Inc.; www.healthnotes.com Colds and Flus Source: Prima Communications, Inc.www.personalhealthzone.com Colorectal Cancer Source: Integrative Medicine Communications; www.drkoop.com Congestive Heart Failure Source: Integrative Medicine Communications; www.drkoop.com Depression Source: Healthnotes, Inc.; www.healthnotes.com Depression Source: Integrative Medicine Communications; www.drkoop.com Depression (Mild to Moderate) Source: Prima Communications, Inc.www.personalhealthzone.com Fibromyalgia Source: Healthnotes, Inc.; www.healthnotes.com Fibromyalgia Source: Integrative Medicine Communications; www.drkoop.com Gallstones Source: Healthnotes, Inc.; www.healthnotes.com Hepatitis Source: Healthnotes, Inc.; www.healthnotes.com High Blood Pressure Source: Integrative Medicine Communications; www.drkoop.com High Cholesterol Source: Prima Communications, Inc.www.personalhealthzone.com
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HIV and AIDS Source: Integrative Medicine Communications; www.drkoop.com Hypertension Source: Integrative Medicine Communications; www.drkoop.com Hypochondriasis Source: Integrative Medicine Communications; www.drkoop.com Insomnia Source: Healthnotes, Inc.; www.healthnotes.com Insomnia Source: Prima Communications, Inc.www.personalhealthzone.com Jet Lag Source: Healthnotes, Inc.; www.healthnotes.com Low Back Pain Source: Integrative Medicine Communications; www.drkoop.com Lupus Source: Integrative Medicine Communications; www.drkoop.com Menopausal Symptoms (Other Than Osteoporosis) Source: Prima Communications, Inc.www.personalhealthzone.com Menopause Source: Healthnotes, Inc.; www.healthnotes.com Menopause Source: Integrative Medicine Communications; www.drkoop.com Migraine Headaches Source: Healthnotes, Inc.; www.healthnotes.com Obesity Source: Integrative Medicine Communications; www.drkoop.com PMS Source: Integrative Medicine Communications; www.drkoop.com Post Traumatic Stress Disorder Source: Integrative Medicine Communications; www.drkoop.com Premenstrual Syndrome Source: Integrative Medicine Communications; www.drkoop.com Prostate Enlargement Source: Integrative Medicine Communications; www.drkoop.com
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Restless Legs Syndrome Source: Healthnotes, Inc.; www.healthnotes.com Sleep Apnea Source: Integrative Medicine Communications; www.drkoop.com Sleeplessness Source: Integrative Medicine Communications; www.drkoop.com Stress Source: Integrative Medicine Communications; www.drkoop.com Stroke Source: Integrative Medicine Communications; www.drkoop.com Systemic Lupus Erythematosus Source: Integrative Medicine Communications; www.drkoop.com Tinnitus Source: Healthnotes, Inc.; www.healthnotes.com Wounds Source: Integrative Medicine Communications; www.drkoop.com •
Alternative Therapy Acupressure Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,662,00.html Acupuncture Source: Healthnotes, Inc.; www.healthnotes.com Aromatherapy Source: Integrative Medicine Communications; www.drkoop.com Aromatherapy Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,664,00.html Ayurveda Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,672,00.html Bach Flower Remedies Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,673,00.html
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Biofeedback Source: Healthnotes, Inc.; www.healthnotes.com Biofeedback Source: Integrative Medicine Communications; www.drkoop.com Biofeedback Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,675,00.html Crystal Healing Alternative names: crystal therapeutics crystal therapy crystal work Source: The Canoe version of A Dictionary of Alternative-Medicine Methods, by Priorities for Health editor Jack Raso, M.S., R.D. Hyperlink: http://www.canoe.ca/AltmedDictionary/c.html Feldenkrais Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,695,00.html Hydrotherapy Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,705,00.html Light Therapy Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,713,00.html Macrobiotics Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,714,00.html Magnet Therapy Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,715,00.html Meditation Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,717,00.html Qigong Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,729,00.html
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Reflexology Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,730,00.html Relaxation Techniques Source: Integrative Medicine Communications; www.drkoop.com Repressed Memory Therapy Alternative names: RMT Source: The Canoe version of A Dictionary of Alternative-Medicine Methods, by Priorities for Health editor Jack Raso, M.S., R.D. Hyperlink: http://www.canoe.ca/AltmedDictionary/r.html Shiatsu Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,733,00.html •
Chinese Medicine Ankun Zanyu Wan Alternative names: (An Kun Zan Yu Wan) Source: Pharmacopoeia Commission of the Ministry of Health, People's Republic of China Anshen Buxin Wan Alternative names: Anshen Buxin Pills Source: Pharmacopoeia Commission of the Ministry of Health, People's Republic of China Baihe Alternative names: Lily Bulb; Baihe (Bai He); Bulbus Lilii Source: Chinese Materia Medica Baizi Yangxin Wan Alternative names: Baizi Yangxin Pills Source: Pharmacopoeia Commission of the Ministry of Health, People's Republic of China Baiziren Alternative names: Chinese Arborvitae Kernel; Semen Platycladi Source: Chinese Materia Medica Bushen Yinao Pian Alternative names: Bushen Yinao Tablets Source: Pharmacopoeia Commission of the Ministry of Health, People's Republic of China
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Cishi Alternative names: Magnetite; Magnetitum Source: Chinese Materia Medica Colla Corii Asini Alternative names: Donkey-hide Glue; %Colla Corii Asini%% Source: Pharmacopoeia Commission of the Ministry of Health, People's Republic of China Dandouchi Alternative names: Fermented Soybean; Semen Sojae Preparatum Source: Chinese Materia Medica Danshen Alternative names: Danshen Root; Radix Salviae Miltiorrhizae Source: Chinese Materia Medica Dengxincao Alternative names: Common Rush; Medulla Junci Source: Chinese Materia Medica Fuling Alternative names: Indian Bread; Poria Source: Chinese Materia Medica Gengnian'an Pian Alternative names: Gengnian'an Tablets Source: Pharmacopoeia Commission of the Ministry of Health, People's Republic of China Hyperlink: http://www.newcenturynutrition.com/cgilocal/patent_herbs_db/db.cgi?db=default&Chinese=Gengnian%27an%20Pian&mh =10&sb=---&view_records=View+Records Hamayou Alternative names: Forest Frog's Oviduct; Oviductus Ranae Source: Chinese Materia Medica Hehuanhua Alternative names: Albizia Flower; Flos Albiziae Source: Chinese Materia Medica Hehuanpi Alternative names: Silktree Albizia Bark; Cortex Albiziae Source: Chinese Materia Medica Huanglian Alternative names: Golden Thread; Rhizoma Coptidis Source: Chinese Materia Medica Huashanshen Alternative names: Funneled Physochlaina Root; Radix Physochlainae Source: Chinese Materia Medica
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Lianzi Alternative names: Szechwan Chinaberry Fruit; Chuanlianzi; Fructus Toosendan Source: Chinese Materia Medica Lianzixin Alternative names: Lotus Plumule; Plumula Nelumbinis Source: Chinese Materia Medica Longyanrou Alternative names: Longan Aril; Longyanrou (Long Yan Rou); Arillus Longan Source: Chinese Materia Medica Luobumaye Alternative names: Dogbane Leaf; Folium Apocyni Veneti Source: Chinese Materia Medica Maidong Alternative names: Liriope Root Tuber; Shanmaidong; Radix Liriopes Source: Chinese Materia Medica Mayou Alternative names: Castor Oil; Bimayou; Oleum Ricini Source: Chinese Materia Medica Muli Alternative names: Oyster Shell; Concha Ostreae Source: Chinese Materia Medica Naolejing Alternative names: Naolejing Syrup Source: Pharmacopoeia Commission of the Ministry of Health, People's Republic of China Qingnao Jiangya Pian Alternative names: Qingnao Jiangya Tablets Source: Pharmacopoeia Commission of the Ministry of Health, People's Republic of China Qiwei Guangzao Wan Alternative names: Qiwei Guangzao Pills Source: Pharmacopoeia Commission of the Ministry of Health, People's Republic of China Renshen Alternative names: Ginseng Leaf; Renshenye (Ren Shen Ye); Folium Ginseng Source: Chinese Materia Medica Sangshen Alternative names: Mulberry Fruit; Fructus Mori Source: Chinese Materia Medica
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Shanmaidong Alternative names: Liriope Root Tuber; Radix Liriopes Source: Chinese Materia Medica Shiwuwei Chenxiang Wan Alternative names: Shiwuwei Chenxiang Pills; Shiwuwei Chenxiang Wan
(Shi Wu Wei Chen Xiang Wan) Source: Pharmacopoeia Commission of the Ministry of Health, People's Republic of China Shouwuteng Alternative names: Tuber Fleeceflower Stem; Caulis Polygoni Multiflori Source: Chinese Materia Medica Suanzaoren Alternative names: Spine Date Seed; Semen Ziziphi Spinosae Source: Chinese Materia Medica Tianwang Buxin Wan Alternative names: Tianwang Buxin Pills; Tianwang Buxin Wan
(Ti An Wang Bu Xin Wan) Source: Pharmacopoeia Commission of the Ministry of Health, People's Republic of China Wuweizi Alternative names: Chinese Magnoliavine Fruit; Fructus Schisandrae Source: Chinese Materia Medica Yuanzhi Alternative names: Thinleaf Milkwort Root; Radix Polygalae Source: Chinese Materia Medica Zhenzhu Alternative names: Nacre; Zhenzhumu; Concha Margaritifera Usta Source: Chinese Materia Medica Zhenzhumu Alternative names: Nacre; Concha Margaritifera Usta Source: Chinese Materia Medica Zhuru Alternative names: Bamboo Shavings; Caulis Bambusae in Taeniam Source: Chinese Materia Medica Zhusha Alternative names: Cinnabar; Cinnabaris Source: Chinese Materia Medica Zishiyin Alternative names: Fluorite; Fluoritum Source: Chinese Materia Medica
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Homeopathy Aconitum Napellus Source: Healthnotes, Inc.; www.healthnotes.com Arsenicum Album Source: Healthnotes, Inc.; www.healthnotes.com Calcarea Phosphorica Source: Healthnotes, Inc.; www.healthnotes.com Cocculus Source: Healthnotes, Inc.; www.healthnotes.com Coffee Cruda Source: Healthnotes, Inc.; www.healthnotes.com Ignatia Source: Healthnotes, Inc.; www.healthnotes.com Kali Phosophoricum Source: Healthnotes, Inc.; www.healthnotes.com Lycopodium Source: Healthnotes, Inc.; www.healthnotes.com Nux Vomica Source: Healthnotes, Inc.; www.healthnotes.com Silicea (Silica) Source: Healthnotes, Inc.; www.healthnotes.com Sulphur Source: Healthnotes, Inc.; www.healthnotes.com Zincum Metallicum Source: Healthnotes, Inc.; www.healthnotes.com
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Herbs and Supplements 5-htp Source: Integrative Medicine Communications; www.drkoop.com 5-htp (5-hydroxytryptophan) Source: Prima Communications, Inc.www.personalhealthzone.com 5-hydroxytryptophan Source: Healthnotes, Inc.; www.healthnotes.com 5-hydroxytryptophan (5-htp) Source: Integrative Medicine Communications; www.drkoop.com
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Acanthopanax Senticosus Source: Integrative Medicine Communications; www.drkoop.com Adrenal Extract Source: Healthnotes, Inc.; www.healthnotes.com American Ginseng Alternative names: Panax quinquefolius Source: Healthnotes, Inc.; www.healthnotes.com American Ginseng Alternative names: Panax quinquefolium Source: Integrative Medicine Communications; www.drkoop.com American Scullcap Alternative names: Scutellaria lateriflora Source: Healthnotes, Inc.; www.healthnotes.com Amino Acids Overview Source: Healthnotes, Inc.; www.healthnotes.com Andrographis Source: Prima Communications, Inc.www.personalhealthzone.com Antibiotic Combination: Sulfa Drugs Source: Integrative Medicine Communications; www.drkoop.com Antituberculosis Agents Source: Integrative Medicine Communications; www.drkoop.com Arctostaphylos Uva Ursi Source: Integrative Medicine Communications; www.drkoop.com Ashwagandha Source: Prima Communications, Inc.www.personalhealthzone.com Asian Ginseng Alternative names: Panax ginseng Source: Healthnotes, Inc.; www.healthnotes.com Asian Ginseng Alternative names: Panax ginseng Source: Integrative Medicine Communications; www.drkoop.com Astragalus Source: Prima Communications, Inc.www.personalhealthzone.com Ava Source: Integrative Medicine Communications; www.drkoop.com Barbiturates Source: Healthnotes, Inc.; www.healthnotes.com
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Bearberry Source: Integrative Medicine Communications; www.drkoop.com Beargrape Source: Integrative Medicine Communications; www.drkoop.com Benzodiazepines Source: Healthnotes, Inc.; www.healthnotes.com Benzodiazepines Source: Prima Communications, Inc.www.personalhealthzone.com Black Cohosh Alternative names: Cimicifuga racemosa Source: Healthnotes, Inc.; www.healthnotes.com Brahmi Alternative names: Centella asiatica , Centella, March Pennywort, Indian Pennywort, Hydrocotyle, Brahmi (Sanskrit), Luei Gong Gen (Chinese)(Note: Gotu kola should not be confused with kola nut.) Source: Integrative Medicine Communications; www.drkoop.com Camellia Sinensis Source: Integrative Medicine Communications; www.drkoop.com Catnip Alternative names: Nepeta cataria Source: Healthnotes, Inc.; www.healthnotes.com Centella Source: Integrative Medicine Communications; www.drkoop.com Centella Asiatica Alternative names: Centella asiatica , Centella, March Pennywort, Indian Pennywort, Hydrocotyle, Brahmi (Sanskrit), Luei Gong Gen (Chinese)(Note: Gotu kola should not be confused with kola nut.) Source: Integrative Medicine Communications; www.drkoop.com Cephalosporins Source: Integrative Medicine Communications; www.drkoop.com Chamomile Alternative names: Matricaria recutita Source: Healthnotes, Inc.; www.healthnotes.com Chamomile Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,766,00.html
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Coleus Alternative names: Coleus forskohlii Source: Healthnotes, Inc.; www.healthnotes.com Coleus Forskohlii Source: Prima Communications, Inc.www.personalhealthzone.com Corydalis Alternative names: Corydalis turtschaninovii, Corydalis yanhusuo Source: Healthnotes, Inc.; www.healthnotes.com Diphenhydramine Source: Healthnotes, Inc.; www.healthnotes.com Dmae Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10023,00.html Dong Quai Source: Prima Communications, Inc.www.personalhealthzone.com Doxylamine Source: Healthnotes, Inc.; www.healthnotes.com Eleuthero Source: Healthnotes, Inc.; www.healthnotes.com Eleuthero Source: Integrative Medicine Communications; www.drkoop.com Eleutherococcus Senticosus Source: Integrative Medicine Communications; www.drkoop.com English Lavendar Source: Integrative Medicine Communications; www.drkoop.com Ephedra Alternative names: Ephedra sinica, Ephedra intermedia, Ephedra equisetina Source: Healthnotes, Inc.; www.healthnotes.com Ephedra Alternative names: Ephedra sinensis, Ma huang Source: Integrative Medicine Communications; www.drkoop.com Ephedra Source: Prima Communications, Inc.www.personalhealthzone.com Ephedra (Ma Huang) Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,777,00.html
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Ephedra Sinensis Source: Integrative Medicine Communications; www.drkoop.com French Lavendar Source: Integrative Medicine Communications; www.drkoop.com Gaba Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10027,00.html Ginseng Source: Prima Communications, Inc.www.personalhealthzone.com Ginseng (panax) Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10029,00.html Glutamine Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10030,00.html Gotu Kola Alternative names: Centella asiatica , Centella, March Pennywort, Indian Pennywort, Hydrocotyle, Brahmi (Sanskrit), Luei Gong Gen (Chinese)(Note: Gotu kola should not be confused with kola nut.) Source: Integrative Medicine Communications; www.drkoop.com Green Tea Alternative names: Camellia sinensis Source: Healthnotes, Inc.; www.healthnotes.com Green Tea Alternative names: Camellia sinensis Source: Integrative Medicine Communications; www.drkoop.com Green Tea Source: Prima Communications, Inc.www.personalhealthzone.com Green Tea Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10032,00.html He Shou Wu Source: Prima Communications, Inc.www.personalhealthzone.com Herbal Decongestant Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com
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Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,949,00.html Herbal Medicine Source: Healthnotes, Inc.; www.healthnotes.com Hops Alternative names: Humulus lupulus Source: Healthnotes, Inc.; www.healthnotes.com Hops Source: Prima Communications, Inc.www.personalhealthzone.com Hops Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Hydantoin Derivatives Source: Integrative Medicine Communications; www.drkoop.com Hydrocotyle Source: Integrative Medicine Communications; www.drkoop.com Hypericum Perforatum Source: Integrative Medicine Communications; www.drkoop.com Indian Pennywort Source: Integrative Medicine Communications; www.drkoop.com Jamaica Dogwood Alternative names: Piscidia erythrina, Piscidia piscipula Source: Integrative Medicine Communications; www.drkoop.com Jamaican Dogwood Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Kava Source: Prima Communications, Inc.www.personalhealthzone.com Kava Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,798,00.html Kava Kava Alternative names: Piper methysticum, Ava Source: Integrative Medicine Communications; www.drkoop.com Klamathweed Source: Integrative Medicine Communications; www.drkoop.com
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Lavandula Angustifolia Source: Integrative Medicine Communications; www.drkoop.com Lavender Alternative names: Lavandula officinalis Source: Healthnotes, Inc.; www.healthnotes.com Lavender Alternative names: Lavandula angustifolia, English Lavendar, French Lavendar Source: Integrative Medicine Communications; www.drkoop.com Lavender Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,799,00.html Lemon Balm Alternative names: Melissa officinalis Source: Healthnotes, Inc.; www.healthnotes.com Loop Diuretics Source: Integrative Medicine Communications; www.drkoop.com Ma Huang Source: Integrative Medicine Communications; www.drkoop.com Macrolides Source: Integrative Medicine Communications; www.drkoop.com Mad-dog Skullcap Source: Integrative Medicine Communications; www.drkoop.com Marsh Pennywort Alternative names: Centella asiatica , Centella, March Pennywort, Indian Pennywort, Hydrocotyle, Brahmi (Sanskrit), Luei Gong Gen (Chinese)(Note: Gotu kola should not be confused with kola nut.) Source: Integrative Medicine Communications; www.drkoop.com Melatonin Source: Healthnotes, Inc.; www.healthnotes.com Melatonin Source: Integrative Medicine Communications; www.drkoop.com Melatonin Source: Prima Communications, Inc.www.personalhealthzone.com Melatonin Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,804,00.html
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Melissa Source: Prima Communications, Inc.www.personalhealthzone.com NADH Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10047,00.html Oxazepam Source: Healthnotes, Inc.; www.healthnotes.com Panax Ginseng Source: Integrative Medicine Communications; www.drkoop.com Panax Quinquefolium Source: Integrative Medicine Communications; www.drkoop.com Passiflora Alternative names: Passion Flower; Passiflora alata L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Passiflora Incarnata Alternative names: Passionflower Source: Integrative Medicine Communications; www.drkoop.com Passion Flower Alternative names: Passiflora incarnata Source: Healthnotes, Inc.; www.healthnotes.com Passion Flower Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Passionflower Alternative names: Passiflora incarnata Source: Integrative Medicine Communications; www.drkoop.com Passionflower Source: Prima Communications, Inc.www.personalhealthzone.com Penicillin Derivatives Source: Integrative Medicine Communications; www.drkoop.com Phenelzine Source: Healthnotes, Inc.; www.healthnotes.com Phenobarbital Source: Healthnotes, Inc.; www.healthnotes.com Phosphatidylserine (PS) Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com
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Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,813,00.html Piper Methysticum Source: Integrative Medicine Communications; www.drkoop.com Piscidia Erythrina Source: Integrative Medicine Communications; www.drkoop.com Piscidia Piscipula Source: Integrative Medicine Communications; www.drkoop.com Pregnenolone Source: Healthnotes, Inc.; www.healthnotes.com Quinolones Source: Integrative Medicine Communications; www.drkoop.com Reishi Alternative names: Ganoderma lucidum Source: Healthnotes, Inc.; www.healthnotes.com SAMe (S-Adenosylmethionine) Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,818,00.html Schisandra Alternative names: Schisandra chinensis Source: Healthnotes, Inc.; www.healthnotes.com Scutellaria Lateriflora Source: Integrative Medicine Communications; www.drkoop.com Siberian Ginseng Alternative names: Eleutherococcus senticosus, Acanthopanax senticosus, Eleuthero Source: Integrative Medicine Communications; www.drkoop.com Siberian Ginseng Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,821,00.html Skullcap Alternative names: Scutellaria lateriflora, Mad-dog Skullcap Source: Integrative Medicine Communications; www.drkoop.com Skullcap Source: Prima Communications, Inc.www.personalhealthzone.com
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Skullcap Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca St. John's Wort Alternative names: Hypericum perforatum, Klamathweed Source: Integrative Medicine Communications; www.drkoop.com St. John's Wort Source: Prima Communications, Inc.www.personalhealthzone.com St. John's Wort Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,824,00.html Tetracycline Derivatives Source: Integrative Medicine Communications; www.drkoop.com Theophylline Derivatives Source: Integrative Medicine Communications; www.drkoop.com Triazolam Source: Healthnotes, Inc.; www.healthnotes.com Uva Ursi Alternative names: Arctostaphylos uva ursi, Bearberry, Beargrape Source: Integrative Medicine Communications; www.drkoop.com Valerian Alternative names: Valeriana officinalis Source: Healthnotes, Inc.; www.healthnotes.com Valerian Alternative names: Valeriana officinalis Source: Integrative Medicine Communications; www.drkoop.com Valerian Source: Prima Communications, Inc.www.personalhealthzone.com Valerian Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Valerian Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10064,00.html Valeriana Alternative names: Valerian; Valeriana officinalis Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org
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Valeriana Officinalis Source: Integrative Medicine Communications; www.drkoop.com Vasodilators Source: Integrative Medicine Communications; www.drkoop.com Wormwood Alternative names: Artemisia absinthium Source: Healthnotes, Inc.; www.healthnotes.com Yohimbe Alternative names: Pausinystalia yohimbe Source: Healthnotes, Inc.; www.healthnotes.com Zizyphus Alternative names: Jujube; Ziziphus sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Zolpidem Source: Healthnotes, Inc.; www.healthnotes.com
General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.
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CHAPTER 4. DISSERTATIONS ON INSOMNIA Overview In this chapter, we will give you a bibliography on recent dissertations relating to insomnia. 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 “insomnia” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on insomnia, we have not necessarily excluded non-medical dissertations in this bibliography.
Dissertations on Insomnia 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 insomnia. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: •
A Comparison of Relaxation and 'structured Day' As Treatment for Insomnia by Lynch, Eileen Marie, PhD from Boston College, 1988, 142 pages http://wwwlib.umi.com/dissertations/fullcit/8922250
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A Cross-sectional Analysis of Depression, Anxiety, and Insomnia by Taylor, Daniel John; PhD from The University of Memphis, 2003, 39 pages http://wwwlib.umi.com/dissertations/fullcit/3095685
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An Examination of Effectiveness of a Sleep Induction Audiotape in Conjunction with a Standardized Behavioral Treatment Protocol on Anxiety, Depression, Psychosocial Functioning, and Sleep among a Clinical Population with Insomnia by Dunn, Jeffrey Allan; PhD from The Florida State University, 2001, 304 pages http://wwwlib.umi.com/dissertations/fullcit/3021555
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Auricular Therapy and Insomnia in the Elderly by Suen, Kwai Ping Lorna; PhD from Hong Kong Polytechnic University (People's Republic of China), 2002, 269 pages http://wwwlib.umi.com/dissertations/fullcit/3039238
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Critical Insomnia: Reading and Rereading Joyce, Proust, and Beckett (ireland; France; Great Britain) by Nesbitt, Lois Ellen, PhD from Princeton University, 1988, 261 pages http://wwwlib.umi.com/dissertations/fullcit/8800321
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Effects of a Paradoxical 'giving-up' Treatment for Chronic, Self-defined Insomnia by Fogle, Dale O; PhD from University of Waterloo (Canada), 1980 http://wwwlib.umi.com/dissertations/fullcit/NK49770
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Effects of Therapist Contact and a Self-help Manual in the Treatment of Sleep-onset Insomnia by Bailey, Carole Anne; PhD from Concordia University (Canada), 1982 http://wwwlib.umi.com/dissertations/fullcit/NK61896
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Insomnia (original Writing) by Minerva, Elizabeth Anne, PhD from The Florida State University, 1997, 290 pages http://wwwlib.umi.com/dissertations/fullcit/9729709
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Locus-of-control and Adjustment Related to Outcome of Two Treatments for Insomnia. by Koffmann, Andrew, PhD from The University of Connecticut, 1976, 177 pages http://wwwlib.umi.com/dissertations/fullcit/7714474
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Non-specific Effects in the Behavioural Treatment of Insomnia by Tookey, Herbert B; PhD from York University (Canada), 1980 http://wwwlib.umi.com/dissertations/fullcit/NK47865
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On the Edge of Night: an Existential Phenomenological Investigation of Transient/situational Insomnias by Polizzi, Liesel Marx; PhD from Duquesne University, 2003, 152 pages http://wwwlib.umi.com/dissertations/fullcit/3080968
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Predictors of Interest in Non-pharmacologic Treatment for Insomnia among Older Primary Care Patients with Disturbed Sleep: an Application of the Self-regulatory Model of Illness Behavior by Cahn, Stacey Colman; PhD from Rutgers the State University of New Jersey - New Brunswick, 2003, 113 pages http://wwwlib.umi.com/dissertations/fullcit/3092921
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The Circadian Rhythms of Core Body Temperature, Serum Cortisol and Serum Melatonin Patterns of Disruption in Chronic Insomnia of Chronobiologic Origin by MacFarlane, James Gordon; PhD from McMaster University (Canada), 1990 http://wwwlib.umi.com/dissertations/fullcit/NL57959
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The Efficacy of Short-term Group Cognitive-behavioral Therapy in the Treatment of Insomnia in the Severely and Persistently Mentally Ill by Mitchell, Jessica Louise; PhD from City University of New York, 2002, 62 pages http://wwwlib.umi.com/dissertations/fullcit/3037423
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The Use of Flotation Rest in the Treatment of Persistent Psychophysiological Insomnia by Ballard, Elizabeth Jean; PhD from The University of British Columbia (Canada), 1989 http://wwwlib.umi.com/dissertations/fullcit/NL50648
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 INSOMNIA Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning insomnia.
Recent Trials on Insomnia The following is a list of recent trials dedicated to insomnia.8 Further information on a trial is available at the Web site indicated. •
Behavioral and Pharmacological Treatment for Insomnia Condition(s): Sleep Initiation and Maintenance Disorders; Sleep Disorders, Intrinsic Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The specific aims of this study are to (a) evaluate the short- and longterm effects of cognitive-behavior therapy (CBT), alone and in combination with medication (zolpidem), for chronic insomnia; (b) compare the efficacy of different maintenance strategies for combining drug and nondrug insomnia therapies to optimize long-term outcomes; and (c) examine the clinical impact of treatment on daytime functioning and psychological well-being. Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00042146
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Combined Behavioral/Pharmacological Therapy for Insomnia Condition(s): Sleep Initiation and Maintenance Disorders; Sleep Deprivation Study Status: This study is currently recruiting patients.
8
These are listed at www.ClinicalTrials.gov.
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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 •
Valerian to Improve Sleep in Patients with Parkinson's Disease Condition(s): Insomnia; Parkinson's Disease Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Complementary and Alternative Medicine (NCCAM) Purpose - Excerpt: The purpose of this trial is to test the short-term effectiveness of valerian, a medicinal herb, to improve sleep in patients with Parkinson's disease (PD). Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00070928
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Yoga as a Treatment for Insomnia Condition(s): Insomnia Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Complementary and Alternative Medicine (NCCAM) Purpose - Excerpt: The purpose of this study is to evaluate the effectiveness of a daily, 8week treatment for insomnia using yoga, relaxation exercises or sleep hygiene. ***PARTICIPANTS MUST LIVE IN THE METROPOLITAN BOSTON AREA IN ORDER TO ENROLL IN THIS STUDY*** Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00033865
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Behavioral Insomnia Therapy for Fibromyalgia Condition(s): Fibromyalgia; Insomnia Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: This study tests the effectiveness of a nondrug treatment for the insomnia that often occurs in people with fibromyalgia. The treatment is a type of psychotherapy called cognitive-behavioral therapy. Cognitive-behavioral therapy combines cognitive therapy, which can modify or eliminate thought patterns contributing to the person's symptoms, and behavioral therapy, which aims to help the person change his or her behavior.
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Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000397 •
Pharmacological and Behavioral Treatment of Insomnia Condition(s): Lung Diseases; Sleep; Sleep Initiation and Maintenance Disorders Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: to develop the maximally effective treatment strategy for chronic sleep-onset insomnia and to reduce its impact on psychological functioning, health, and economic sequelae. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005753
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Study of Melatonin: Sleep Problems in Alzheimer's Disease Condition(s): Alzheimer Disease; Dyssomnias Study Status: This study is completed. Sponsor(s): National Institute on Aging (NIA) Purpose - Excerpt: This protocol is a multicenter clinical trial of melatonin for sleep disturbances associated with Alzheimer's disease (AD). Frequent nocturnal awakening is a common behavioral symptom of AD. Nighttime wandering and agitated behavior may result in injuries and sleep disruption for caregivers. Alternatives are sorely needed to the currently available sleep medications that have marginal efficacy and serious side effects. Melatonin is a naturally occurring hormone secreted by the pineal gland. It has soporific effects with oral administration and is well tolerated. It enhances sleep in normal older people. Melatonin also may help sleep disturbances associated with AD; however, this remains to be proven. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000171
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
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5,400 visitors daily. To access this database, simply go to the Web site at http://www.clinicaltrials.gov/ and search by “insomnia” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: •
For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/
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For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html
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For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/
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For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm
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For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm
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For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm
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For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp
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For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm
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For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/
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For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm
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For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm
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For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm
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For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm
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For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm
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For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials
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CHAPTER 6. PATENTS ON INSOMNIA Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.9 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “insomnia” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on insomnia, we have not necessarily excluded non-medical patents in this bibliography.
Patents on Insomnia By performing a patent search focusing on insomnia, 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
9Adapted
from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.
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will tell you how to obtain this information later in the chapter. The following is an example of the type of information that you can expect to obtain from a patent search on insomnia: •
Assessment and modification of a subject's endogenous circadian cycle Inventor(s): Allan; James S. (Pittsburgh, PA), Czeisler; Charles A. (Cambridge, MA), Kronauer; Richard E. (Cambridge, MA) Assignee(s): Brigham and Women's Hospital (Boston, MA) Patent Number: 5,163,426 Date filed: June 26, 1987 Abstract: A method for accurately assessing and rapidly modifying the phase and amplitude of the endogenous circadian pacemaker is disclosed. A circadian cycle modification capacity assessment method comprises (before and after a stimulus) eliminating activity-related confounding factors associated with the sleep-rest cycle which otherwise mask the state of the endogenous circadian pacemaker. Based on either individual or normative assessment data, the circadian phase and amplitude modification method involves the application of bright (about 9,500 lux) light and, advantageously, episodes of imposed darkness, at critically chosen phases to achieve rapid and stable changes in phase and amplitude. The timing of the episodes of bright light may be chosen either by reference to empirically-derived phase response data, or by using a mathematical model in which the endogenous circadian pacemaker is a van der Pol oscillator. A forcing function in the model is substantially proportional to changes in the cube root of the surrounding illuminance, in lux. The amplitude of the endogenous circadian pacemaker may actually be reduced to substantially zero, so as to bring about dramatic phase modifications in diminishingly small periods of time. The methods find special utility in treating "jet lag" sufferers, shift workers, advanced circadian phase experienced by many elderly subjects, and those afflicted with delayed sleep phase insomnia. Excerpt(s): This invention relates to methods and devices for assessing and modifying the circadian cycle in humans. More specifically, the invention relates to methods and devices for using scheduled exposure to bright light, and advantageously also periods of darkness, to alter the circadian cycle of humans to a desired phase and amplitude. It is known in the art that humans exhibit circadian (daily) cycles in a variety of physiologic, cognitive, and behavioral functions. The cycles are driven by an internal biological clock or circadian pacemaker which has been located in the brain and are not just passive responses to periodic environmental changes. It is known that humans exhibit different degrees of alertness, performance, and proneness to accidents at different phases in their circadian cycle. Often, the activities in which humans wish to engage do not coincide in time with the most appropriate point in the circadian cycle. For instance, transmeridian travelers experience what is commonly referred to as "jet lag." This phenomenon occurs when the internal, physiological circadian phase of the traveler has not yet adapted to the geophysical time of his destination. Individuals who travel from west to east often experience sleeplessness late in the evening at their destination, with a corresponding difficulty in awakening on time in the morning. Similarly, those who travel from east to west often experience a tendency to sleep earlier in the evening and arise earlier in the morning than is appropriate for the locale of their destination. The travelers' internal, physiological cycle lags (or leads) their desired activity-rest cycle. Symptoms are worse and last longer when travelers must cross more than three or four time zones, especially when traveling west to east. West to east travel is more difficult than east to west travel
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because the intrinsic period of the human circadian pacemaker is greater than 24 hours (averaging about 24.3 to 25.0 hours in normal young men). Therefore, in the absence of an environmental synchronizing cue, the phase position of the pacemaker tends to drift to a later hour (i.e., in a manner equivalent to westward travel at a rate of about one time zone per 2 days). The insomnia associated with jet lag may be postponed two or three days if the travelers are sleep-deprived as a result of the journey, since sleep deprivation makes it easier to sleep at any circadian phase. However, the essential circadian nature of jet lag is demonstrated by nocturnal insomnia and excessive daytime sleepiness which typically occur within two to three days of arrival. Web site: http://www.delphion.com/details?pn=US05163426__ •
Coffee substitute Inventor(s): Zhao; Iris G (1969 Zonal Ave., Los Angeles, CA 90033) Assignee(s): none reported Patent Number: 6,171,635 Date filed: January 27, 1999 Abstract: A coffee-type beverage base is prepared by light roast method under 200.degree. C. and originated from grain and legume. This coffee substitute has a pleasant aroma, and can be used as a carrier of nutritional supplement or herb therapy as well as an additive of coffee, tea, or chocolate. This novel drink is especially suitable for individuals who suffer from conditions making them coffee intolerant, e.g., pregnancy, or those who suffer form hypoglycemia, hypertension, arrhythmia, insomnia, or gastric irritation. Excerpt(s): The present invention relates to coffee substitutes and, more particularly, to a non-caffeine beverage base produced from grain and legume, which provide synergetic coaction among the ingredients. Until the middle of this century, development of medical treatment for human disease was intimately connected with the plant kingdom. Major breakthroughs such as digitalis, aspirin, morphine, vincristin and antibiotics have resulted from the study and usage of natural products. Gaps remain between the prescribed pharmaceutical pills and natural food therapy. The human body contains about 55-60% water. Humans by nature enjoy drinking liquids. Liquids containing energy supply, mineral, nutritional supplement and medicine are always the first choice for a patient after surgery and IV nutrition. Coffee possesses a pleasant aroma and is an enjoyable taste experience that many believe reduces stress during the workday. Consequently, the United States consumes about 70% of the world's coffee crop, or about 3 cups a day for each American. Coffee beverages contain about 100 mg caffeine per cup (per 8 ounces). Coffee stimulates the central nervous system, increases diuresis, dilates the vascular system and combats sleep, which is possibly linked to the caffeinemediated glycogen sparing effect secondary to an increased rate of lipolysis. Web site: http://www.delphion.com/details?pn=US06171635__
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Cranial nerve stimulation treatments using neurocybernetic prosthesis Inventor(s): Zabara; Jacob (200 Locust, Apt. 22D, Philadelphia, PA 19106) Assignee(s): none reported Patent Number: 5,540,734 Date filed: September 28, 1994 Abstract: The treatment, control or prevention of medical, psychiatric or neurological disorders may be accomplished by application of modulating electric signals to one or both of a patient's trigeminal and glossopharyngeal nerves. The disorders treatable, controllable or preventable by such nerve stimulation include voluntary and involuntary disorders, migraine, epileptic seizure, motor disorders, Parkinson's disease, cerebral palsy, spasticity, chronic nervous illnesses and involuntary movement; pancreatic endocrine disorders including diabetes and hypoglycemia; dementia including cortical, subcortical, multi-infarct, Alzheimer's disease and Pick's disease; sleep disorders including central sleep apnea, insomnia and hypersomnia; eating disorders including anorexia nervosa, bulimia and compulsive overeating; and neuropsychiatric disorders including schizophrenia, depression and borderline personality disorder. Excerpt(s): The present invention generally relates to methods for treating, controlling or preventing medical, psychiatric or neurological disorders by application of modulating electrical signals to a selected nerve or nerve bundle of a patient, and more particularly to techniques for treating patients with migraine, epileptic seizures, involuntary motor disorders, chronic nervous illnesses, pancreatic endocrine disorders, dementia, eating disorders and neuropsychiatric disorders. Methods and apparatus for treating or controlling medical, psychiatric or neurological disorders by application of modulating electrical signals to a selected nerve or nerve bundle of the patient, are recognized in the art. The majority of these techniques stimulate one or more nerves which terminate on the target tissue. For example, it is known to stimulate the phrenic nerve, which terminates on the diaphragm, to effect respiration. There are relatively few reports of methods and apparatus which function to stimulate the brain and thereby cause the brain to send signals to the target tissue. The prior art directed to this latter approach to treat or control medical, psychiatric or neurological disorders is directed to the application of electric signals to the vagus and carotid sinus nerves, using an implantable or external neurostimulating device. The use of nerve stimulation to treat endocrine disorders is disclosed in U.S. Pat. No. 5,231,988, which states that electrical stimulation of the vagus nerve can treat the pancreatic disorders of hypoglycemia and diabetes mellitus. Web site: http://www.delphion.com/details?pn=US05540734__
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Drug-withdrawal-syndrome auricle-therapeutic device Inventor(s): Qingmin; Wu (Room 102, Flat 4, 17# Huaxin Xiang, Nanjing, Jiangsu Province, CN) Assignee(s): none reported Patent Number: 6,296,652 Date filed: May 26, 1999
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Abstract: A device for treating the undesirable symptoms resulting from cessation of habitual drug use, which can include insomnia, anxiety, tremors, loss of appetite, drowsiness, nausea, and sweating, and for reducing the rate of recurrence of drug use following treatment through the use of a programmed series of acupuncture, massage, and/or moxibustion treatments of acupuncture points in a subject's ear(s). The device includes a housing that conforms to the contour of a human ear containing a plurality of acupuncture needles held in an elastomeric structure and connected to a movable elongate member such that the plurality of needles may be brought into intermittent contact with the inner surface of the ear with an approximately equal force. The device further includes a control circuit adapted to automatically control the application of acupuncture stimulating current, moxibustion, and/or massage in a programmable manner. The device allows a user to program a treatment regimen into the device, removably affix the device adjacent at least one of a subject's ears, and provide the programmed acupuncture, moxibustion, and/or massage treatments to a plurality of known acupuncture points on the inner surface of the subject's ear(s). In one embodiment, the acupuncture needles are made of a permanently magnetic material to include an auxiliary magnetic treatment. In an alternative embodiment, the device also includes a vocal and/or musical sound generating component as additional therapy. Excerpt(s): The invention concerns a therapeutic device, particularly, a therapeutic device for treating drug withdrawal syndrome. What is called drug withdrawal syndrome means such serious syndrome as being anger for drug, anxiety, frequently giving yawn, sweating, running with tears, running nose, drowsing, dilated pupil, being goose flesh, tremor, shivering, muscle aching, headache, losing appetite, insomnia, even blood pressure rising, frequency and depth of breath increasing, pulse quickening, restless, nausea, curling, vomiting, diarrhea, spermatorrhea, etc. occurred after stopping drug-taking. Chemotherapy of entire course integrated the three phases addictionremoving, consolidation and rehabilitation is adopted in drug-giving-up treatment now. Body acupuncture and ear acupuncture therapies by hand-needling or electroimpulse output only are used for an auxiliary means. Modern drug-giving-up therapy is a pure chemotherapy. Addiction-removing therapy taking opium acceptor analeptic such as methadone, opium, dihydroetorphine and others or opium acceptor partial analeptic-buprenorphine as alternatives, or addiction-removing taking non-opium clonidine, existing preserving treatment taking naltrexone or methadone in consolidation therapy. The above-mentioned therapies, generally speaking, have many advantages such as reliable efficiency, fast addiction-removing action and relative safety. While there exist problems with them. These include more undesirable reaction, heavier toxic side effects, undetermined effect in giving up abuse of many drugs due to addiction to narcotic drug, trend of some medicines producing dependence, consequently treating medicines having been turned new narcotic drugs and leading new addiction to them. After addiction-removed by modern drug-giving-up treatment, some procrastinated withdrawal syndromes still exists at different extents with sufferers, even though taking naltrexone to consolidate effect, 90.about.95% drug-retaking rate still occurs during six months after addiction-removing treatment using different giving-up medicines in modern drug-giving-up therapy, in result, the vicious circle of habituation--addictionremoving--Addiction-recovering--addiction-re-removi ng almost can not be broken. The existing acupuncture or ear acupuncture therapy and electronics designed based the principle of science of acupuncture and moxibustion is a pure physical therapy, and is only used as an auxiliary means. Hand-needling treatment is not easy to master exactly and may cause pain and infection due to improper operation. Drug-giving-up effect may be unsatisfactory and unsteady when design of the devices is unreasonable, or the
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devices are not convenient to use due to their low automatic degree. Consequently, popularization of the treatment method in the drug-giving-up field is blocked. Web site: http://www.delphion.com/details?pn=US06296652__ •
Herbal formulations with nacre Inventor(s): Yng-Wong; Quing Non (5524 MacArthur Blvd., Washington, DC 20016) Assignee(s): none reported Patent Number: 5,807,554 Date filed: April 11, 1997 Abstract: Various complex formulations including the nacre form of calcium as a primary constituent are provided for dealing with a number of human ailments including insomnia, skin inflammation and itching, and anxiety disorders, and for increasing bone density. For bone density increase nacre is the main constituent, but the complex also includes sources of plant and/or animal collagen. The other compositions include nacre along with herbs to facilitate use of the nacre for treatment of various ailments or conditions. Excerpt(s): Nacre (also known as Pearl Powder, Concha Margarita, Amber Poria Pearl, Concha Margaritaferae, marine calcium, and Mother of Pearl) is an excellent source of calcium and has been used by generations of Chinese to soothe restlessness, anxiety, and stress. It has been used with children, even newborn infants, to calm or cure seizures, epileptic episodes, and brain functions. It is also used with adults for these same conditions and also for senile memory problems. Western laboratory sciences have tracked neurotransmission to the molecular level of electron exchanges. Calcium is central in receiving and sending signals from one nerve cell to another. The balance of calcium within the nerve cell is crucial to maintaining the health of the cell, the life or death of the cell. Calcium helps maintain the electrical energy capacity within the appropriate range for the specific nerve cells and helps absorb and eject toxins when they enter a cell. It is not surprising, then, that the health of the calcium transport system at the cellular level in nerve cells both reflects the health of the body as whole and affects the capacity of the body to withstand injury, invasion and stress. In 1993, Chinese laboratory research found memory improved because acetylcholinesterase activity was inhibited with nacre based formulae. Calcium utilization, however, is low compared with calcium intake in the normal U.S. diet. Until recent identification of the preference of amino acids for nacre over other sources of calcium there has been no satisfactory explanation for this. One likely reason amino acids prefer nacre as their source of calcium was identified in Chinese laboratory research which identified amino acids as proportionately high in nacre. This makes it easy for alien amino acids to be attached to and to utilize nacre as a source of calcium and is an advantage other inorganic calcium sources cannot provide. Web site: http://www.delphion.com/details?pn=US05807554__
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Low dose temazepam Inventor(s): Sterling; William R. (Pine Brook, NJ) Assignee(s): Sandoz Pharm. Corp. (E. Hanover, NJ) Patent Number: 5,030,632 Date filed: August 17, 1990 Abstract: This invention relates to a hard gelatin capsule containing no more than 5 to 10 milligrams of crystalline temazepam and its use in the treatment of transient insomnia. Excerpt(s): This invention relates to a new pharmaceutical form of temazepam and its use as a hypnotic agent. More particularly, it relates to a low dose hard gelatin temazepam capsule and its use in the treatment of insomnia, especially, transient insomnia. Temazepam, whose chemical name is 7-chloro-1,3-dihydro-3-hydroxy-1methyl-5-phenyl-2H-1,4-benzodiazepin-2-on e is a well known hypnotic agent used in the treatment of insomnia. The commercial product is sold in the United States in the form of hard gelatin capsules containing 15 and 30 milligrams of temazepam. Soft gelatin capsules containing 10 and 20 milligrams of temazepam are also available abroad. The hard gelatin capsule has been studied in great depth and has been found to be generally effective at doses of 15 and 30 milligrams of temazepam. At doses of 10 and 20 milligrams, the soft gelatin capsules have also been found to be effective, although Nicholson, et al. (Br. J. Clin. Pharmac., 3,543-550,1976) have reported that at 10 milligrams, no change in total sleep time was found, whereas at 20 milligrams, total sleep time was markedly increased. Lower dose forms of temazepam containing 5 milligrams of the compound have been used in a number of investigations (LaReforma Medica, 16,425-427, 1970; Bombay Hosp. J., 16,222-223,1974; Neuropsychobiology 9(1),52-65,1983) but have never been found to be useful in treating insomnia. In the Neuropsychobiology publication, the authors indicate that at 5 milligrams, temazepam is known to be of no clinical importance as a hypnotic agent. Web site: http://www.delphion.com/details?pn=US05030632__
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Massaging and combing helmet for insomnia Inventor(s): In; Cho N. (5 Wayside La., Ashland, MA 01721) Assignee(s): none reported Patent Number: 5,081,986 Date filed: September 7, 1990 Abstract: A massaging helmet contains an endless belt which rubs the wearer's head with belt areas of various textures. The belt runs over two rollers located inside the helmet near the forehead and nape. An electric motor and batteries power the belt, which rubs the scalp from front to back. The rear roller is adjustable for tensioning the belt. The belt surface, of soft plastic, has both an embossed area to mimic the human hand, and another area with rows of upright plastic fingers which comb the hair. Excerpt(s): The present invention relates to head-massaging machines to relieve insomnia. Head massage for relaxation is very old. Primitive man, lacking implements, used the palms of the hands for head massage, and fingers to comb the hair. Head massage and grooming are practiced by all peoples and also by all animals related to man, such as the baboons who spend much time grooming one another's heads to remove insects and dirt. Head massage is used by parents to sooth and reward their
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children; the related act of head patting indicates approval or affection to children and adults both. The universal human use of these actions probably indicates that they are genetically based. Because head massage induces warm and contented feelings, it is an effective relaxation promoter. Because it is relaxing, it is also effective against insomnia. Web site: http://www.delphion.com/details?pn=US05081986__ •
Matrix which contains nephrite jade powder as a main component Inventor(s): Kim; Jun-Han (#102-902 Hanjoo Apartment, Twaegye-dong 944, Choonchun-Shi, Kangwon-do, KR) Assignee(s): none reported Patent Number: 5,879,797 Date filed: August 15, 1996 Abstract: The present invention relates to a novel matrix containing nephrite jade powder as a main component. By using the matrix, a variety of goods in the field of medical goods, utensil goods, equipments for leisure time, vessels, interior goods, agricultural goods, industrial goods, fishery goods, traffic goods, transportation goods, equipments for sports, electronic instruments, precision instrument, or the like can be prepared. The goods made of the matrix can show excellent effects of treating pathological symptoms (headache, numb feeling, indigestion, insomnia, or the like), removing impurities (such as heavy metals), improving the quality of water, promoting the growth of plants by virtue of the inherent properties of nephrite jade. Excerpt(s): The present invention relates to a matrix containing fine powder of nephrite jade as a main component. More specifically, the present invention relates to the matrix containing fine powder of nephrite jade of very fine combination weave fibrous microstructure of cryptocrystalline tremolite type. By using the matrix, a variety of goods in the field of medical goods, utensil goods, equipments for leisure time, vessels, interior goods, agricultural goods, industrial goods, fishery goods, traffic goods, transportation goods, equipments for sports, electronic instruments, precision instrument, or the like can be prepared. The goods made of the matrix can show excellent effects of treating pathological symptoms (headache, numb feeling, indigestion, insomnia, or the like), removing impurities (such as heavy metals), improving the quality of water, promoting the growth of plants by virtue of the inherent properties of nephrite jade. As is generally known, jade is largely divided into jadeite and nephrite jade. Web site: http://www.delphion.com/details?pn=US05879797__
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Method and system for applying low energy emission therapy Inventor(s): Barbault; Alexandre (Colmar, FR), Chang; Rea-Woun (Singapore, SG), Kunz; Henry (Zurich, CH), Kuster; Niels (Zurich, CH), Lebet; Jean-Pierre (Montreaux, CH), Pasche; Boris (New York, NY) Assignee(s): Symtonic, S.A. (CH) Patent Number: 5,441,528 Date filed: September 25, 1992
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Abstract: A low energy emission therapy system is provided which includes an emitter of low energy electromagnetic emissions and a probe for applying the emissions to a patient under treatment. The emitter emits a high frequency electromagnetic emission in the form of a carrier signal modulated by a plurality of modulation signals. The invention also includes an impedance transformer located intermediate the emitter and the probe in order to match the impedance of the patient with that of the output of the emitter. Particular modulation signal frequencies and application times and sequences are provided for the treatment of insomnia, and for the treatment of general anxiety disorder which may include panic attacks. Excerpt(s): The invention relates to systems and methods for applying low energy emission therapy for the treatment of central nervous system disorders. Low energy emission therapy involving application of low energy electromagnetic emissions to a patient has been found to be an effective mode of treating a patient suffering from central nervous system (CNS) disorders such as generalized anxiety disorders, panic disorders, sleep disorders including insomnia, circadian rhythm disorders such as delayed sleep, psychiatric disorders such as depression, obsessive compulsive disorders, disorders resulting from substance abuse, sociopathy, post traumatic stress disorders or other disorders of the central nervous system. Apparatus and methods for carrying out such treatment are described in U.S. Pat. Nos. 4,649,935 and 4,765,322, assigned to the same assignee as the present application, the disclosures of which are expressly incorporated herein by reference. Since the time of these earlier disclosures, a substantially greater understanding of the mechanisms of the treatment and how to secure best results has been gained, which has led to important developments being made to the apparatus (herein described as a system). Although the apparatus and methods described in the above patents have provided satisfactory results in many cases, consistency and significance of results has sometimes been lacking. Also, it was not always possible to properly control or monitor the duration of treatment or the quantities or nature of the low energy emissions being applied to the patient. Furthermore, the efficiency of transfer of the low energy emissions to the patient was limited and was affected by such factors as patient movement, outside interference and the like. Web site: http://www.delphion.com/details?pn=US05441528__ •
Method for increasing the amplitude of P300 waves in the human brain Inventor(s): Braverman; Eric (844 Rte. 518, Skillman, NJ 08558) Assignee(s): none reported Patent Number: 5,163,444 Date filed: October 5, 1990 Abstract: A cranial electrotherapy stimulation ("CES") device which generates electrical pulses is applied between the forehead and wrist area of a human being in order to affect electrical activity in the brain and thereby decrease the individual's craving for controlled substances such as alcohol and drugs and reduce anxiety, insomnia and depression. A portable cranial electrical stimulator is preferably attached to the arm area or about the waist of a patient. A first electrode is attached to the forehead of the patient, preferably above the bridge of the nose between the eyes, and a second electrode is attached to the wrist area of one arm, preferably at the radial artery. Electrical pulses having an amplitude in the range of 0.1 to 1.5 mA and a frequency of approximately 100 Hz are applied for at least 20 minutes at a 20% duty cycle between the forehead and the
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wrist electrodes. As a result, electrical activity in the brain is affected, in particular, the amplitude of P300 electrical brain activity is increased. Since decreased P300 activity is associated with increased patient interest in drugs and alcohol, the use of the CES in this way makes it less likely that the patient will desire such controlled substances. Excerpt(s): The invention relates to a method and apparatus for increasing electrical brain activity, in particular the amplitude of P300 waves, thereby decreasing cravings for addictive substances by providing cranial electrical stimulation between the forehead and wrist area of a patient. P300 waves are electrical waves which occur in the human brain. They are a cognitive evoked potential in response to a stimulus to the brain known as an "oddball paradigm of beeps". The P300 wave occurs at approximately 300 ms from the initial stimulation of a patient with the oddball paradigm and are measured using a quantified EEG machine such as a device known as a BEAM ("Brain Electrical Activity Map"). The "P" stands for "Positive". Various researchers have correlated a diminished activity of P300 waves with an increase in craving for alcohol and other addictive drugs. See e.g., Begleiter & Projesz, Neuroele Processes in Individuals at Risk for Alcoholism, Alcohol & Alcoholism, Vol, 25:251-256 (1990); Begleiter, Projesz, Rawlinos & Echardt, Auditory Recovery Function and P3 in Boys at High Risk for Alcoholism, Alcohol, Vol. 4:315-321 (1987); Begleiter & Projesz, The P300 Component of the Event-Related Brain Potential in Psychiatric Patients, Evoked Potential, 529-535, New York: Alan R. Liss, Inc. (1986); Whipple, Parker & Noble, An Atypical Neurocognitive Profile in Alcoholic Fathers and Their Sons, Journal of Studies on Alcohol, Vol. 43:240-244 (1988); Polich, Burns, & Bloom, P300 and the Risk for Alcoholism. Clinical and Experimental Research, Vol. 12:248-254 (1988); Schukits, Gold, Croot, Finn & Polich, P300 Latency After Ethanol Inoestion in Sons of Alcoholics and in Controls. Biological Psychiatry, Vol. 24:310-315 (1988); O'Connor, Hesselbroch, Tasman, Depalma, P3 Amplitudes in Two Distinct Tasks are Decreased in Young Men with a History of Paternal Alcoholism, Alcohol Vol. 4:323-330 (1987). The amplitude of P300 waves is a measure of concentration, attention and anxiety. An increase in P300 wave amplitude probably has applications beyond a decrease in cravings for alcohol and drugs (i.e., reduction of anxiety, depression and insomnia). Cranial Electrotherapy Stimulation ("CES") is a term applied by the U.S. Food and Drug Administration ("FDA") to the transcranial application of small amounts of electricity, usually less than 1.5 mA at 100 Hz, to the head of a human being. It was originally used in the 1960's to induce sleep. Web site: http://www.delphion.com/details?pn=US05163444__ •
Method for treating anxiety, anxiety disorders and insomnia Inventor(s): Chouinard; Guy (4015 Chemin Trafalgar, Montreal, CA) Assignee(s): none reported Patent Number: 6,372,792 Date filed: January 29, 1998 Abstract: Treatment of the anxiety disorders and insomnia in humans may be accomplished by administering gabapentin in an effective amount. Excerpt(s): This invention relates to treatment of anxiety, including all of the anxiety disorders, and insomnia in humans by administration of gabapentin, its derivatives and pharmaceutically acceptable salts. Gabapentin is a generic term used to identify the chemical compound (1-aminomethyl)-1-cyclohexaneacetic acid. It is useful in therapy of
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certain cerebral disorders such as certain forms of epilepsy, faintness attacks, hypokinesia and cranial traumas. U.S. Pat. Nos. 4,024,175 and 4,087,544 cover the compound and its uses. They also disclose an acid salt, i.e. gabapentin hydrochloride hydrate in a ratio of 4:4:1 and a sodium salt of gabapentin hydrate in a ratio of 2:1. These patents are hereby incorporated by reference. Pregabalin is a long-acting form of gabapentin with the formula (S)-3-(aminomethyl)-5-methyl-hexanoic acid and CAS Registry Number: 148553-50-8, CI 1008. The compounds are described in U.S. Pat. Nos. 5,608,090 and 5,599,973, the disclosure of which are incorporated herein by reference to show additional forms of gabapentin usable in this invention. U.S. Pat. No. 5,084,479 states that compounds such as gabapentin are used for treating neurodegenerative disorders, perinatal asphyxia, status epilepticus, Alzheimer's, Huntington's, Parkinson's, and Amyotrophic Lateral Sclerosis. That invention covers treating neurodegenerative disorders termed acute brain injury. These include but are not limited to: stroke, head trauma, and asphyxia. Web site: http://www.delphion.com/details?pn=US06372792__ •
Method for treating insomnia Inventor(s): Tran; Pierre Van (Carmel, IN) Assignee(s): Eli Lilly and Company (Indianapolis, IN) Patent Number: 5,744,470 Date filed: February 10, 1997 Abstract: The invention provides a method for treating insomnia comprising administering an effective amount of olanzapine to a patient in need thereof. Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/013,126, filed Mar. 11, 1996. This invention provides a method for using 2-methyl-4(4-methyl-1-piperazinyl)-10H-thieno›2,3-b!›1,5!benzodiazepine, (hereinafter referred as "olanzapine"), for the treatment of insomnia. Insomnia is one of the most common complaints in general medical practice. There is a one year prevalance of as high as 40%. DSM-IV, p. 553 (American Psychiatric Association, Washington, D.C. 1994). A variety of pharmacological agents are used to treat insomnia; however, the "perfect" agent would allow sleep to occur, with normal sleep architecture, rather than produce a pharmacologically altered sleep pattern. The "perfect" agent would not cause next-day effects, either rebound anxiety or continued sedation. There continues to be a need for more desirable drugs having at least several of the characteristics described for the "perfect" agent. Web site: http://www.delphion.com/details?pn=US05744470__
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Method of detecting prions in a sample and transgenic animal used for same Inventor(s): Prusiner; Stanley B. (San Francisco, CA), Scott; Michael R. (San Francisco, CA), Telling; Glenn (San Francisco, CA) Assignee(s): The Regents of the University of California (Alameda, CA) Patent Number: 5,565,186 Date filed: May 13, 1994
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Abstract: Prions are protein based infectious material that cause of variety of diseases such as Scrapie, bovine spongiform encephalopathy (also known as "Mad Cow" disease), Creutzfeldt Jakob Disease, Kuru, and fatal familial insomnia. The invention is directed to artificial prion genes that are made up of elements of the prion genes of a host and test species. When these artificial prion genes are inserted into a transgenic mouse, the resultant mouse becomes susceptible to infection with prions that infect the test species but do not normally infect mice. The transgenic animals are useful for testing for the presence of prions in a sample. Excerpt(s): This invention relates generally to chimeric genes, methods of assaying and to transgenic animals used in such assays. More specifically, this invention relates to artificial and chimeric PrP genes, assaying samples for pathogenic prions, and to transgenic mice containing an artificial or chimeric PrP gene. Prions are infectious pathogens that cause central nervous system spongiform encephalopathies in humans and animals. Prions are distinct from bacteria, viruses and viroids. The predominant hypothesis at present is that no nucleic acid component is necessary for infectivity of prion protein. Further, aprion which infects one species of animal (e.g., a human) will not infect another (e.g., a mouse). A major step in the study of prions and the diseases that they cause was the discovery and purification of a protein designated prion protein ("PrP") [Bolton et al., Science 218:1309-11 (1982); Prusiner et al., Biochemistry 21:6942-50 (1982); McKinley et al., Cell 35:57-62 (1983)]. Complete prion protein-encoding genes have since been cloned, sequenced and expressed in transgenic animals. PrP.sup.C is encoded by a single-copy host gene [Basler et al., Cell 46:417-28 (1986)] and is normally found at the outer surface of neurons. A leading hypothesis is that prion diseases result from conversion of PrP.sup.C into a modified form called PrP.sup.Sc. However, the actual biological or physiological function of PrP.sup.C is not known. Web site: http://www.delphion.com/details?pn=US05565186__ •
Methods and compositions for treating sleep disorders, convulsive seizures and other disorders using optically pure (+) zopiclone Inventor(s): Brandt; Steven (Marlborough, MA), Young; James W. (Palo Alto, CA) Assignee(s): Sepracor Inc. (Marlborough, MA) Patent Number: 5,786,357 Date filed: August 1, 1994 Abstract: Methods and compositions are disclosed utilizing the optically pure (+) isomer of zopiclone. This compound is a potent drug for the treatment of sleep disorders, such as insomnia, and convulsive disorders, such as epilepsy. Similarly, these novel compositions and methods are useful for the treatment of sleep disorders and convulsive disorders while avoiding the concomitant liability of adverse effects associated with the racemic mixture of zopiclone. The optically pure (+) isomer of zopiclone is also useful for treating disorders that are affected by the binding of agonists to central nervous system or peripheral benzodiazepine receptors. Also described are methods and compositions for treating disorders that are affected by binding of agonists to central nervous system or peripheral benzodiazepine receptors while avoiding the adverse effects associated with the administration of the racemic mixture of zopiclone. Excerpt(s): This invention relates to novel compositions of matter containing optically pure (+) zopiclone. These compositions possess potent activity in treating sleep disorders such as insomnia. These compositions also possess potent activity in treating
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sleep disorders while avoiding the usual adverse effects including but not limited to bitter taste in the mouth, drowsiness, tiredness in the morning and headache, which are associated with the administration of the racemic mixture of zopiclone. The novel compositions of this invention also possess potent activity in treating convulsive disorders such as epilepsy. These novel compositions useful in treating convulsive disorders avoid the adverse effects which are associated with the administration of the racemic mixture of zopiclone. Additionally, these novel compositions of matter containing optically pure (+) zopiclone are useful in treating disorders that are affected by the binding of agonists to central nervous system and peripheral benzodiazepine receptors. Such disorders include but are not limited to anxiety, aggressive behavior, muscle tension, behavioral disorders, depression, schizophrenia, and disorders associated with abnormal plasma hormone levels such as endocrine disorders. These novel compositions of matter are useful in treating disorders that are affected by the binding of agonists to central nervous system and peripheral benzodiazepine receptors while avoiding the adverse effects associated with the administration of the racemic mixture of zopiclone. Also disclosed are methods for treating the above-described conditions or disorders in a human by administering the (+) isomer of zopiclone to said human. Further disclosed are methods for treating the above-described conditions while avoiding the adverse effects that are associated with the racemic mixture of zopiclone, by administering the (+) isomer of zopiclone to said human. Web site: http://www.delphion.com/details?pn=US05786357__ •
Methods of using and compositions comprising N-desmethylzolpidem Inventor(s): Jerussi; Thomas P. (Framingham, MA) Assignee(s): Sepracor, Inc. (Marlborough, MA) Patent Number: 6,333,345 Date filed: May 4, 2000 Abstract: The invention is directed to compositions comprising, and methods of using, N-desmethylzolpidem in the treatment and prevention of diseases and conditions in mammals. Examples of such diseases and conditions include, but are not limited to: sleep disorders such as insomnia; affective disorders such as depression, attention deficit disorder, and attention deficit disorder with hyperactivity or attention deficit/hyperactivity disorder; convulsive disorders such as epilepsy; anxiety; aggressive behavior; spasticity or acute muscle spasm; behavioral disorders; schizophrenia; and disorders associated with abnormal plasma hormone levels such as endocrine disorders. Excerpt(s): The invention relates to compositions and methods for the treatment and prevention of sleep, convulsive, and related disorders. A 2:1 tartrate complex of zolpidem is sold under the tradename AMBIEN.RTM. and is indicated for the shortterm treatment of insomnia. Physicians' Desk Reference, 2929-2933 (53.sup.rd ed. 1999). The synthesis of zolpidem is described by U.S. Pat. Nos. 4,382,938 and 4,794,185. Zolpidem binds at or near benzodiazepine receptors, particularly those found within GABA.sub.A receptor chloride channel macromolecular complexes located in the central nervous system. Scatton, B., et al., J. Pharmacol. Exp. Ther. 237(2):659-665 (1986); Criswell, H. E., et al., Neuropharmacology 36(11-12):1641-1652 (1997); Buhr, A. and Sigel, E., Proc Natl. Acad Sci USA 94(16):8824-8829 (1997). At least three subtypes of benzodiazepine, or omega (.omega.), receptors are believed to exist within GABA.sub.A receptor complexes, but zolpidem preferentially binds in vitro to the.omega.sub.1
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receptor. Physicians' Desk Reference, 2929 (53.sup.rd ed. 1999). The sedative, anticonvulsant, anxiolytic, and myorelaxant properties of zolpidem are believed to be due to its ability to allosterically modulate the activity of GABA.sub.A complexes by increasing trans-membrane conductance of chloride ions. This stabilizes neuronal membrane potentials and dampens excitatory input. Id.; Goodman & Gilman's The Pharmacological Basis of Therapeutics, Hardman, J. G., et al., eds., 365-372 (9.sup.th ed., 1996). Web site: http://www.delphion.com/details?pn=US06333345__ •
Methods, compositions, and compounds for allosteric modulation of the GABA receptor by members of the androstane and pregnane series Inventor(s): Belelli; Delia (Rowland Heights, CA), Bolger; Michael (Los Alamitos, CA), Gee; Kelvin W. (Hacienda Heights, CA), Lan; Nancy C. (S. Pasadena, CA), Mirsadeghi; Seid (Sherman Oaks, CA), Purdy; Robert (San Antonio, TX) Assignee(s): University of Southern California (Los Angeles, CA) Patent Number: 5,232,917 Date filed: August 13, 1991 Abstract: Method, compositions, and compounds for modulating brain excitability to alleviate stress, anxiety, insomnia and seizure activity using certain steroid derivatives that act at a newly identified site on the gamma-aminobutyric acid receptor-chloride ionophore (GR) complex. Excerpt(s): The present invention is directed to a method, compositions, and compounds for modulating animal brain excitability via the gamma-aminobutyric acid (GABA) receptor-chloride ionophore complex (GR complex). Brain excitability is defined as the level of arousal of an animal, a continuum that ranges from coma to convulsions, and is regulated by various neurotransmitters. In general, neurotransmitters are responsible for regulating the conductance of ions across neuronal membranes. At rest, the neuronal membrane possesses a potential (or membrane voltage) of approximately -80 mV, the cell interior being negative with respect to the cell exterior. The potential (voltage) is the result of ion (K.sup.+, Na.sup.+, Cl.sup.-, organic anions) balance across the neuronal semi-permeable membrane. Neurotransmitters are stored in presynaptic vesicles and are released under the influence of neuronal action potentials When released into the synaptic cleft, an excitatory chemical transmitter such as acetylcholine will cause membrane depolarization (change of potential from -80 mV to -50 mV). This effect is mediated by postsynaptic nicotinic receptors which are stimulated by acetylcholine to increase membrane permeability to Na.sup.+ ions. The reduced membrane potential stimulates neuronal excitability in the form of a postsynaptic action potential. In the case of the GR complex, the effect on brain excitability is mediated by GABA, a neurotransmitter. GABA has a profound influence on overall brain excitability because up to 40% of the neurons in the brain utilize GABA as a neurotransmitter. GABA regulates the excitability of individual neurons by regulating the conductance of chloride ions across the neuronal membrane. GABA interacts with its recognition site on the GR complex to facilitate the flow of chloride ions down an electrochemical gradient of the GR complex into the cell. An intracellular increase in the levels of this anion causes hyperpolarization of the transmembrane potential, rendering the neuron less susceptible to excitatory inputs (i.e., reduced neuron excitability). In other words, the higher the chloride ion concentration, the lower the brain excitability (the level of arousal).
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Web site: http://www.delphion.com/details?pn=US05232917__ •
Optical device and method for using same Inventor(s): Anderson; Duncan J. (London, GB) Assignee(s): Migra Limited (GB) Patent Number: 5,092,669 Date filed: March 16, 1990 Abstract: Apparatus is disclosed for directing flashes of light into the eyes of a user. LED's 17 are mounted in the eyepieces of goggles 3 or spectacles 43 to face the eyes of a wearer. The goggles 3 or spectacles 43 are opaque and are provided with opaque flanges 9 to avoid ambient light reaching the eyes of a wearer. The frequency and brightness of the flashes is variable. The device is useful in the treatment of migraine, pre-menstrual syndrome, insomnia and nervous tension. Alternatives are disclosed using remote light sources 51 and optic fibres 53 or mirrors 57, mechanical or electro-optic shutters 59, 61, and arrangements using a common light source 51 for both eyes. Excerpt(s): The present invention relates to apparatus for delivering flashes of light to the eyes, and to methods of using the apparatus. The invention has particular, but not exclusive, application to the treatment and prevention of migraine, pre-menstrual syndrome, insomnia and nervous tension. Attention is directed to the applicant's publication "The Treatment of Migraine with Variable Frequency Photo-Stimulation" D. J. Anderson, Headache, Mar. 1989, pages 154 and 155, which is incorporated herein by reference. The following definition of migraine has been given in J. N. Blau "Towards a Definition of Migraine Headache", Lancet, 1984, 1, pages 444 to 445. "Episodic headache lasting from 2 to 72 hours with total freedom between attacks. The headaches must be associated with visual or gastrointestinal disturbance or both. The visual symptoms occur as an aura before and/or photophobia during the headache phase. If there are no visual but alimentary disturbances, then vomiting must feature in some attacks." An alternative definition is given in "Classification of headache disorders, cranial neuralgias and facial pain; and diagnostic criteria for primary headaches disorders" available from the International Headache Society and abbreviated from Cephalalgia 1988; 8 suppl. 7:169, which is incorporated herein by reference. Pre-menstrual syndrome has been defined as "the cyclic occurrence of symptoms that are of sufficient severity to interfere with some aspects of life and which appear with consistent and predictable relationship to menses" in Endicott J., Halbreich U., Schacht S. and Nee J. "Premenstrual changes and affective disorders" Journal of Psychosomatic Medicine 1981, Vol. 43, page 519, and quoted in "The Premenstrual Syndromes" ed. L. H. Gise, published 1988 by Churchill Livingstone, New York, Edinburgh, London, Melbourne. Web site: http://www.delphion.com/details?pn=US05092669__
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Physiological monitoring Inventor(s): Dadswell; Michael Richard (Oxon, GB), Laister; Mark Jeremy (Oxford, GB), Pardey; James (Oxford, GB), Tarassenko; Lionel (Oxford, GB) Assignee(s): Oxford Medical Limited (Oxon, GB) Patent Number: 5,999,846 Date filed: November 8, 1996
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Abstract: An insomnia or vigilance monitor comprising one or more electrodes (1a,1b) for obtaining an electrical signal from a subject over a period of epochs, the electrical signal being related to the sleep or wakefulness stage type being experienced by the subject; and a processor (5) adapted to analyze the electrical signal and assign a sleep or wakefulness stage type to each epoch to generate a hypnogram. Methods of monitoring sleep or vigilance using the mastoid site are also disclosed. Further disclosures relate to a method of training and testing a first neural network for use in a physiological monitor, and a method of assigning a class to an epoch of a physiological signal obtained from a subject as a set of samples. Excerpt(s): The present invention relates to improvements in physiological monitoring, in particular sleep or vigilance monitoring. The method currently employed world-wide for scoring sleep recordings is described in Rechtschaffen and Kales (1968), "A Manual of Standardized Technology, Techniques and Scoring System for Sleep Stages of Human Subjects". chin muscle tone (electromyogram (EMG))--from a pair of electrodes under the chin. Web site: http://www.delphion.com/details?pn=US05999846__ •
Prevention or treatment of insomnia with a neurokinin-1 receptor antagonist Inventor(s): Mendel; Carl M. (Short Hills, NJ), Waldstreicher; Joanne (Scotch Plains, NJ) Assignee(s): Merck & Co. Inc. (Rahway, NJ) Patent Number: 6,525,073 Date filed: October 16, 2001 Abstract: A tachykinin antagonist is useful, alone or in conjunction with other agents, for altering circadian rhythmicity and alleviating circadian rhythm disorders and for enhancing and improving the quality of sleep. Excerpt(s): Circadian rhythms are exhibited by all eukaryotic plants and animals, including man. Biological rhythms are periodic fluctuations in biological processes over time, including circadian as well as seasonal variations. Circadian, or approximately 24hour, rhythms include the production of biological molecules such as hormones, the regulation of body temperature, and behavior such as wakefulness, alertness, sleep and periods of activity. Circadian rhythms are endogenous, self-sustained oscillations over 24-hour periods found in organisms ranging from prokaryotes to humans (J S Takahashi, et al. Science. 217,1104-1111 (1982)). In nature, circadian rhythms are closely tied to environmental cues that impose a 24-hour pattern on many of these fluctuations. The regulation of circadian rhythms by signals from the environment involves "entrainment" of the circadian rhythm. The environmental signals which affect entrainment of the circadian rhythm are termed "zeitgebers", an example of which is the light-dark cycle. The control of many circadian rhythms in mammals is mediated by the portion of the brain called the suprachiasmatic nuclei (SCN). In humans as well as other mammals, the circadian clock, which controls all endogenous circadian rhythms, is located in the SCN of the hypothalamus. Activity, alertness, core body temperature, and many hormones all have endogenous circadian rhythms controlled by the SCN. The SCN is the primary pacemaker for circadian rhythms in mammals. Circadian rhythms are primarily entrained by the light-dark cycle. One of the most important and reproducible characteristics of a circadian clock is that it can respond to exogenous light/dark signals. The circadian clock is composed of three parts: light-input pathways, a clock, and effector pathways. Light signals are conveyed by the retina to the SCN, and
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the pineal gland produces melatonin (N-acetyl-5-methoxytryptamine), which is regulated by the SCN. Information regarding light is conveyed from the retina to the SCN via the direct retinohypothalamic tract (RHT), as well as indirectly via the lateral geniculate nucleus (LGN). Web site: http://www.delphion.com/details?pn=US06525073__ •
Rapid method of determining clearance of prion protein Inventor(s): Kozak; Robert W. (Foster City, CA), Lee; Douglas C. (Apex, NC), Petteway; Steve R. (Cary, NC) Assignee(s): Bayer Corporation (Pittsburgh, PA) Patent Number: 6,605,445 Date filed: February 22, 1999 Abstract: Transmissible spongiform encephalopathies (TSEs) are a class of fatal, neurodegenerative diseases found in many mammalian species. Human TSEs include kuru, Creutzfeldt-Jakob disease (CJD), and fatal familial insomnia. Non-human TSEs include sheep scrapie, bovine spongiform encephalopathy (BSE), feline spongiform encephalopathy, and chronic wasting diseases in elk and mule deer. These neurodegenerative diseases are caused by prions and display characteristic amyloid plaque deposition. The only known component of the infectious prion is an abnormal, disease-causing isoform of the prion protein (PrP), called PrP scrapie (PrP.sup.Sc). During a post-translational process, PrP.sup.Sc is formed from the normal, cellular PrP isoform (PrP.sup.C). The scrapie isoform is less soluble, more proteinase-resistant, and more susceptible to aggregation than the wildtype protein. The claimed invention is directed toward a rapid, specific, sensitive, and quantitative method for the detection of TSE clearance from a plasma product utilizing a chemiluminescent Western blot immunoassay. This immunoassay format can detect picogram concentrations of PrP.sup.RES (proteinase resistant PrP fragment) and is linear over a 3-5 log range. The invention is useful for tracking the clearance of PrP.sup.Sc during plasma manufacturing processes. Excerpt(s): The invention relates to a rapid method of detecting pathogen or prion protein that may be use to determine the clearance of pathogen protein, in general, and to a Western blot immunoassay method of relating pathogen protein clearance to infectivity clearance, in specific. The method has been applied to the quantitation of TSE protein clearance and its relationship to infectivity clearance. The Cohn-Oncley purification of therapeutic proteins from blood plasma, referred to herein in general as the Cohn process or scheme, employs a series ethanol additions and pH adjustments to purify or enrich for proteins which may be used in human therapies. Commonly purified proteins include immunoglobulins, anti-hemophiliac factors and albumin. While many manufacturers of such products utilize the basic Cohn scheme, frequently established steps may be modified or additional steps are implemented to increase either the purity and/or yield for a given product. Such steps are typically proprietary for a given manufacturer. Since the discovery that HIV could be carried and transmitted though the use of blood products, the interest and concern about the presence of such pathogenic agents in biological products derived from blood has increased. Most recently, there has been concern that CJD, Creutzfeldt-Jakob Disease, could be transmitted through the use of blood-derived product. CJD is one of the human transmissible spongiform encephalopathies (TSE), a collection of neurodegenerative diseases that are debilitating and fatal. Infectivity associated with CJD appears to be
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either associated with or caused by the prion protein (PrP). Although new disease carrying viruses may be generated at any time, manufacturers of blood-based products take precautions to obtain a blood product that is free of known transmissible diseases, to the extent for which these can be tested. Unfortunately, the primary test for possible TSE infectivity is a biological assay in which rodents are injected with the material of interest to see if infectivity develops. The results of such assays require nine months to a year to develop, frequently too long to hold a manufactured lot of plasma product prior to release for use. Web site: http://www.delphion.com/details?pn=US06605445__ •
Subliminal acoustic manipulation of nervous systems Inventor(s): Loos; Hendricus G. (3019 Cresta Wy., Laguna Beach, CA 92651) Assignee(s): none reported Patent Number: 6,017,302 Date filed: October 31, 1997 Abstract: In human subjects, sensory resonances can be excited by subliminal atmospheric acoustic pulses that are tuned to the resonance frequency. The 1/2 Hz sensory resonance affects the autonomic nervous system and may cause relaxation, drowsiness, or sexual excitement, depending on the precise acoustic frequency near 1/2 Hz used. The effects of the 2.5 Hz resonance include slowing of certain cortical processes, sleepiness, and disorientation. For these effects to occur, the acoustic intensity must lie in a certain deeply subliminal range. Suitable apparatus consists of a portable battery-powered source of weak subaudio acoustic radiation. The method and apparatus can be used by the general public as an aid to relaxation, sleep, or sexual arousal, and clinically for the control and perhaps treatment of insomnia, tremors, epileptic seizures, and anxiety disorders. There is further application as a nonlethal weapon that can be used in law enforcement standoff situations, for causing drowsiness and disorientation in targeted subjects. It is then preferable to use venting acoustic monopoles in the form of a device that inhales and exhales air with subaudio frequency. Excerpt(s): The central nervous system can be manipulated via sensory pathways. Of interest here is a resonance method wherein periodic sensory stimulation evokes a physiological response that peaks at certain stimulus frequencies. This occurs for instance when rocking a baby, which typically provides relaxation at frequencies near 1/2 Hz. The peaking of the physiological response versus frequency suggests that one is dealing here with a resonance mechanism, wherein the periodic sensory signals evoke an excitation of oscillatory modes in certain neural circuits. The sensory pathway involved in the rocking example is the vestibular nerve. However, a similar relaxing response at much the same frequencies can be obtained by gently stroking a child's hair, or by administering weak heat pulses to the skin, as discussed in U.S. Pat. No. 5,800,481, Sep. 1, 1998. These three types of stimulation involve different sensory modalities, but the similarity in responses and effective frequencies suggests that the resonant neural circuitry is the same. Apparently, the resonance can be excited either via vestibular pathways or via cutaneous sensory pathways that carry tactile or temperature information. Near 2.5 Hz another sensory resonance has been found that can be excited by weak heat pulses induced in the skin, as discussed in U.S. Pat. No. 5,800,481, Sep. 1, 1998. This sensory resonance brings on a slowing of certain cortical functions, as indicated by a pronounced increase in the time needed to silently count backward from 100 to 70 with the eyes closed. The effect is sharply dependent on frequency, as shown
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by a response peak a mere 0.13 Hz wide. The thermally excited 2.5 Hz resonance was found to also cause sleepiness, and after long exposure, dizziness and disorientation. Experiments have shown that atmospheric acoustic stimulation of deeply subliminal intensity can excite in a human subject the sensory resonances near 1/2 Hz and 2.5 Hz. The 1/2 Hz resonance is characterized by ptosis of the eyelids, relaxation, drowsiness, a tonic smile, tenseness, or sexual excitement, depending on the precise acoustic frequency near 1/2 Hz that is used. The observable effects of the 2.5 Hz resonance include a slowing of certain cortical functions, sleepiness, and, after long exposure, dizziness and disorientation. The finding that these sensory resonances can be excited by atmospheric acoustic signals of deeply subliminal intensity opens the way to an apparatus and method for acoustic manipulation of a subject's nervous system, wherein weak acoustic pulses are induced in the atmosphere at the subject's ears, and the pulse frequency is tuned to the resonance frequency of the selected sensory resonance. The method can be used by the general public for control of insomnia and anxiety, and for facilitation of relaxation and sexual arousal. Clinical use of the method includes the control and perhaps a treatment of anxiety disorders, tremors, and seizures. A suitable embodiment for these applications is a small portable battery-powered subaudio acoustic radiator which can be tuned to the resonance frequency of the selected sensory resonance. Web site: http://www.delphion.com/details?pn=US06017302__ •
Transdermal administration of short or intermediate half-life benzodiazepines Inventor(s): Dunbar; Darth M. (San Mateo, CA), Sharma; Kuldeepak (Mountain View, CA) Assignee(s): Cygnus Therapeutic Systems (Redwood City, CA) Patent Number: 5,225,198 Date filed: August 27, 1991 Abstract: Method and laminated composite for administering short or intermediate halflife benzodiazepines such as alprazolamine or triazolam transdermally to treat conditions such as anxiety in the case of alprazolam and insomnia in the case of triazolam. The composite comprises an impermeable backing layer and a reservoir layer containing the benzodiazepine and a permeation enhancer combined with a solventbased acrylic polymer adhesive with the amounts of benzodiazepine and enhancer being sufficient to cause the benzodiazepine to pass through the skin at a rate in excess of about one.mu.g/cm.sup.2 /hr. Excerpt(s): This invention relates to methods and devices for administering short- and intermediate-acting benzodiazepines, particularly alprazolam and triazolam, transdermally. Alprazolam (8-chloro-1-methyl-6-phenyl-4H-1,2,4-triazolo(4,3-a) (1,4)benzodiazepine) is a short to intermediate half-life benzodiazepine drug. It is sold commercially in the U.S. under the brand name Xanax in the form of tablets for treatment of anxiety, depression, and panic disorders. U.S. Pat. No. 3,987,052 describes the preparation and oral administration of alprazolam. It is given orally in doses of 0.25 to 0.5 mg with a maximum dose up to 4 mg for adults. Therapeutic plasma concentrations are typically in the 17 to 30 ng/ml range. (USP Drug Information for the Health Care Professional, page 595, 10th Ed., 1990.) The pharmacokinetics and pharmacodynamics of alprazolam after oral and intravenous administration are reported in J. Clin. Psychiatry (1983) 44 (8, Sec. 2) and Psychopharmacology (1984) 84:452-456. Triazolam (8-chloro-6-(2-chlorophenyl)-1-methyl-4H-1,2,4-triazolo-(4,3-a)-
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1,4-benzod iazepine is a short half-life benzodiazepine drug. It is sold commercially in the U.S. under the brand name Halcion in the form of oral tablets for treatment of insomnia. It is given orally at does of 125-250.mu.g. Web site: http://www.delphion.com/details?pn=US05225198__ •
Treatment for insomnia Inventor(s): Kavey; Neil B. (26 W. Orchard Rd., Chappagua, NY 10514) Assignee(s): none reported Patent Number: 5,502,047 Date filed: March 22, 1993 Abstract: A method for the treatment of chronic insomnia is disclosed which involves the administration of low dosages of a compound selected from the pharmaceutically acceptable forms of doxepin, trimipramine, amitriptyline, trazodone and mixtures hereof. Excerpt(s): This invention relates to a method for the treatment of individuals suffering from chronic insomnia. In a preferred embodiment, the present invention relates to a method for the treatment of chronic insomnia in individuals other than those suffering from depression. A large percentage of the adult population suffers from insomnia in some form at some time in their lives. This may vary from an occasional episode to chronic conditions and may involve onset and/or maintenance insomnia. Chronic insomnia is typically accepted to involve episodes greater than three (3) weeks in duration. The effects of sleep deprivation resulting from such insomnia are well known and need not be described herein other than to say that they are to be avoided. Currently, there exist treatments only for acute insomnia. These treatments involve the administration of medication, either of the non-barbiturate or barbiturate type, shortly before bedtime. While both types of sedatives may be used to effectively treat insomnia, neither is without its undesirable side effects. For instance, barbiturate type sedatives, such as secobarbital sodium (sold by Eli Lilly and Company under the tradename of Seconal.RTM.) are general depressants. While effective, these medications are well known to lose their effectiveness after a few days. They are further highly addictive and commonly abused. They are therefore no longer widely prescribed. Web site: http://www.delphion.com/details?pn=US05502047__
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Treatment of transient and short term insomnia Inventor(s): Kavey; Neil B. (26 W. Orchard Rd., Chappaqua, NY 10514) Assignee(s): none reported Patent Number: 6,211,229 Date filed: February 17, 2000 Abstract: The invention is directed to a method for the treatment of a patient suffering from transient or short term insomnia. The claimed method comprises the administration of a compound selected from the group consisting of the pharmaceutically acceptable forms of doxepin, amitriptyline, trimipramine, trazodone and mixtures thereof in dosages ranging from about 0.5 to about 20.0 milligrams.
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Excerpt(s): This invention relates to a method for the treatment of individuals suffering from transient or short term insomnia. A large percentage of the adult population suffers from insomnia in some form at some time in their lives. This may vary from a single episode of one night's duration to chronic conditions. Transient insomnia is an insomnia that is present for one to several days, and is less than one week in duration. Short term insomnia is an insomnia of one to three weeks in duration. Chronic insomnia is typically accepted to involve episodes greater than three (3) weeks in duration. The insomnia may further involve onset insomnia (difficulty in falling asleep) and/or maintenance insomnia (difficulty in maintaining uninterrupted sleep). It is well known that the sleep deprivation resulting from such insomnia adversely affects cognition, safety and quality of life. Known treatments for insomnia include the administration of medication, either of the non-barbiturate or barbiturate type, shortly before bedtime. While both types of sedatives may be used to effectively treat insomnia, neither is without its undesirable side effects. Barbiturate type sedatives, such as secobarbital (sold by Eli Lilly and Company under the tradename of Seconal.RTM.) are general depressants. While effective, these medications are well known to lose their effectiveness after a few days. Furthermore, they are highly addictive and commonly abused. They are therefore no longer widely prescribed. Web site: http://www.delphion.com/details?pn=US06211229__ •
Use of Gaba-analogues for treating insomnia Inventor(s): Magnus; Leslie (Livingston, NJ), Segal; Catherine A. (Chester, NJ) Assignee(s): Warner-Lambert Company (Morris Plains, NJ) Patent Number: 6,306,910 Date filed: January 9, 2001 Abstract: The instant invention is a method of using analogs of glutamic acid and gamma-aminobutyric acid to treat insomnia. Excerpt(s): The present invention relates to the use of analogs of glutamic acid and gamma-aminobutyric acid (GABA) for the treatment of insomnia. Insomnia and sleeplessness are common problems. Often, the insomnia or sleeplessness is precipitated by stress, emotional and physical causes. U.S. Pat. No. 5,510,381, directed to the use of gabapentin to treat mania, mentions one study in which gabapentin has also been found to enhance delta-wave (deep) sleep. This effect is beneficial in acute mania and also leads to reducing the risk for onset of a new episode of mania. Web site: http://www.delphion.com/details?pn=US06306910__
Patent Applications on Insomnia As of December 2000, U.S. patent applications are open to public viewing.10 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to insomnia:
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This has been a common practice outside the United States prior to December 2000.
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Gabapentin analogues for sleep disorders Inventor(s): Bryans, Justin Stephen; (Balsham, GB), Meltzer, Leonard Theodore; (Ann Arbor, MI) Correspondence: Mehdi Ganjeizadeh; Warner Lambert Company; 2800 Plymouth Road; Ann Arbor; MI; 48105; US Patent Application Number: 20030212133 Date filed: December 11, 2002 Abstract: The invention provides a new use of compounds for formula 1 or 1A or a pharmaceutically acceptable salt thereof. The compounds are useful in the treatment of insomnia and related disorders. 1 Excerpt(s): wherein R.sub.1 is hydrogen or a lower alkyl radical and n is 4, 5, or 6 are known in U.S. Pat. No. 4,024,175 and its divisional U.S. Pat. No. 4,087,544. The uses disclosed are: protective effect against cramp induced by thiosemicarbazide; protective action against cardiazole cramp; the cerebral diseases, epilepsy, faintness attacks, hypokinesia, and cranial traumas; and improvement in cerebral functions. The compounds are useful in geriatric patients. The patents are hereby incorporated by reference. U.S. patent application Ser. No. 09/485,382 filed Feb. 8, 2000, covers compounds of formulas 1 and 1A below. The application discloses various utilities for the compounds. This is incorporated by reference. hydrogen, methyl, or carboxyl; or an individual enantiomeric isomer thereof; or a pharmaceutically acceptable salt thereof, are useful in the treatment of insomnia (U.S. Patent Application No. 60/092,166 filed Jul. 9, 1998, which is incorporated here by reference). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Galenical preparations of dapsone and related sulphones, and method of therapeutic and preventative treatment of disease Inventor(s): Aberg, A K Gunnar; (Sarasota, FL), Bain, Allen I; (Vancouver, CA), Zolotoy, Alexander; (Richmond, CA) Correspondence: Kevin S Lemack; Neilds & Lemack; 176 E Main Street; Westboro; MA; 01581; US Patent Application Number: 20030092635 Date filed: August 26, 2002 Abstract: Dapsone and related sulfones are known to have therapeutic activity against leprosy, dermatitis herpetiformis, actinomycotic mycetoma, asthma, malaria, rheumatoid arthritis, Kaposis sarcoma, pneumocystis carini (pneumonia), subcorneal pustular dermatosis and cystic acne, in patients in need of such therapy. These sulfones are also known to have therapeutic activity against memory loss in patients in need of such therapy, including patients suffering from Alzheimer's disease and related neurodegenerative disorders. It has now been found that new, modified-release formulations of dapsone and related sulfones may also be used that decrease side effects and increase effectiveness of the drugs. New methods are disclosed utilizing certain formulations of dapsone and related sulfones that improve the therapeutic index of said drugs. Side effects of these drugs are known to those skilled in the art and include, but are not restricted to anorexia, psychosis, agranulocytosis, peripheral neuritis, hemolysis, methemoglobinemia, nausea, vomiting, headache, dizziness, tachycardia, nervousness,
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insomnia and skin disorders. Modified-release (as defined herein) formulations of dapsone have now been found to avoid some or all of these side effects, and to have more efficacy on potency. Excerpt(s): The object of the present invention pertains to a method of treating or preventing certain diseases in a human being while increasing compliance, reducing side effects and improving efficacy of the active therapeutic ingredient(s) within a large therapeutic range. The method comprises the use of modified-release dosage formulations of sulfone compounds including 4,4'-diaminodiphenylsulfone, its didextrose sulfonate derivative(s), their analogs, metabolites, any enantiomers, any diasteriomers, or mixtures thereof and/or therapeutically acceptable salts thereof. Dapsone is an active substance that is known in the treatment of various infectious diseases and inflammatory conditions. There is a wealth of data and experimental studies regarding the activity of dapsone and related sulfones. In particular, there is a large amount of data regarding the bioavailability and pharmacokinetics of the drug. It is also known in the prior art that dapsone has therapeutic activity against leprosy, dermatitis herpetiformis, actinomycotic mycetoma, asthma, malaria, rheumatoid arthritis, Kaposis sarcoma, pneumocystis carinii (pneumonia), subcorneal pustular dermatosis and cystic acne, in patients in need of such therapy. However, since the acute or chronic toxicity of dapsone is unacceptable at the doses necessary to treat most diseases, it is not possible to use this compound for these indications in the presently available formulation(s). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Liquid pharmaceutical compositions Inventor(s): Kulkarni, Neema M.; (Randolph, NJ), Meyer-Wonnay, Hans; (Emmendingen, DE), Schneider, Michael; (Denzlingen, DE), Silbering, Steven B.; (Forest Hills, NY) Correspondence: Karen Debenedictis; Warner-lambert Company; 2800 Plymouth Road; Ann Arbor; MI; 48105; US Patent Application Number: 20020198261 Date filed: May 28, 2002 Abstract: A liquid pharmaceutical composition of a GABA analog comprising at least one polyhydric alcohol containing 2 to 6 carbon atoms having a pH of about 5.5 to about 7.0 and additionally a two-component liquid pharmaceutical composition comprising a first component comprising a powder mixture comprising a GABA analog and a solid polyhydric alcohol, and a second component comprising a liquid base are described, as well as methods to prepare the compositions and a method for treating cerebral diseases, including epilepsy, faintness attacks, hypokinesia and cranial traumas, neurodegenerative disorders, depression, mania and bipolar disorders, anxiety, panic, inflammation, renal colic, insomnia, gastrointestinal damage, incontinence, pain, including neuropathic pain, muscular pain, skeletal pain, and migraine using a therapeutically effective amount of the pharmaceutical compositions. Excerpt(s): This invention relates to liquid pharmaceutical compositions comprising a gamma-aminobutyric acid (GABA) analog and processes for the preparation of the same as well as methods of using such compositions to treat subjects, including human subjects, suffering from certain cerebral diseases, including epilepsy, faintness attacks, hypokinesia and cranial traumas, neurodegenerative disorders, depression, mania and
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bipolar disorders, anxiety, panic, inflammation, renal colic, insomnia, gastrointestinal damage, incontinence, pain, including neuropathic pain, muscular pain, skeletal pain, and migraine. GABA is an inhibitory amino acid found in the mammalian central nervous system (CNS). It has been reported that dysfunctions with GABA neurotransmission in the CNS may contribute or even cause psychiatric and neurological diseases such as epilepsy, schizophrenia, Parkinson's disease, Huntington's Chorea and dyskinesia (Saletu B., et al., International Journal of Clinical Pharmacology, Therapy, and Toxicology, 1986; 24:362-373). was designed as a GABA analog that would cross the blood-brain barrier. Gabapentin was found to have anticonvulsant and antispastic activity with extremely low toxicity in man. Gabapentin is presently marketed under the trademark Neurontin.RTM. as adjunctive therapy in the treatment of partial seizures in patients with epilepsy. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Method for the treatment of insomnia Inventor(s): Magnus, Leslie; (Livingston, NJ), Segal, Catherine A.; (Chester, NJ) Correspondence: Charles W. Ashbrook; Warner-lambert Company; 2800 Plymouth Road; Ann Arbor; MI; 48105; US Patent Application Number: 20020004528 Date filed: August 3, 2001 Abstract: The instant invention is a method of using certain analogs of glutamic acid and gamma-aminobutyric acid to treat insomnia. Excerpt(s): The present invention relates to the use of analogs of glutamic acid and gamma-aminobutyric acid (GABA) for the treatment of insomnia. GABA analogs are known agents useful in antiseizure therapy for central nervous system disorders such as epilepsy, Huntington's chorea, cerebral ischemia, Parkinson's disease, tardive dyskinesia, and spasticity. It has also been suggested that the compounds can be used as antidepressants, anxiolytics, and antipsychotics. See WO 92/09560 (U.S. Ser. No. 618,692 filed Nov. 27, 1990) and WP 93/23383 (U.S. Ser. No. 886,080 filed May 20, 1992). WO 97/33858 teaches that compounds related to gabapentin are useful or treating epilespy, faintness attacks, hypokinesia, cranial disorders, neurodegenerative disorders, depression, anxiety, panic, pain, and neuropathological disorders. WO 97/33858 does not specify what forms of pain are treated. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Method of treating hypersomnia sleep disturbance or insomnia sleep disturbance that is secondary to another condition Inventor(s): McLeod, Malcolm N.; (Chapel Hill, NC) Correspondence: Jenkins & Wilson, PA; 3100 Tower Blvd; Suite 1400; Durham; NC; 27707; US Patent Application Number: 20020032182 Date filed: July 31, 2001 Abstract: The method of this invention is directed to a treatment of hypersomnia or insomnia that is secondary to another condition in men and women by administering to
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a patient a therapeutically effective amount of chromium in a pharmaceutically acceptable form, for instance in conjunction with the administration of another composition to treat the other condition, such as a standard antidepressant composition, such as a selective serotonin reuptake inhibitor composition. Chromium is administered to the patient at dosages in a preferred range of about 200 to about 500 micrograms chromium. Excerpt(s): This application is a divisional of co-pending U.S. patent application Ser. No. 09/510,135, filed Feb. 22, 2000, herein incorporated by reference, which is a divisional of U.S. patent application Ser. No. 09/025,899 filed Feb. 19, 1998, now U.S. Pat. No. 6,034,125, which is a Divisional of U.S. Patent application Ser. No. 08/901,841, filed Jul. 28, 1997, now U.S. Pat. No. 5,877,171. The present invention relates generally to a treatment for a sleep disturbance, i.e., sleepiness (clinically known as hypersomnia) or insomnia, that is secondary to another condition, i.e., depression or pre-menstrual syndrome, and more particularly to the treatment of sleepiness or insomnia, that is secondary to depression or pre-menstrual syndrome, using chromium. The present invention even more particularly relates to a method of treating the sleepiness or insomnia, that is secondary to depression or pre-menstrual syndrome, by administering chromium to a patient concurrently with the administration of an antidepressant composition, for instance a selective serotonin reuptake inhibitor such as sertraline or paroxetine, to the patient. On the other hand, the invention in the prior Ser. No. 09/510,135 relates generally to a treatment for alcohol craving, to a treatment for depression and to a treatment of pre-menstrual syndrome, and more particularly to the treatment of alcohol craving using chromium, to the treatment of depression using chromium and to the treatment of pre-menstrual syndrome using chromium. The present invention also particularly relates a method of improving the effectiveness of an antidepressant composition by administering chromium to a patient concurrently with the administration of an antidepressant composition to the patient. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
PHARMACEUTICAL USES FOR NOS INHIBITORS Inventor(s): LOWE, JOHN A. III; (STONINGTON, CT) Correspondence: Pfizer Inc; 150 East 42nd Street; 5th Floor - Stop 49; New York; NY; 10017-5612; US Patent Application Number: 20020151572 Date filed: August 11, 1999 Excerpt(s): The present invention relates to new pharmaceutical uses for compounds that exhibit activity as nitric oxide synthase (NOS) inhibitors. Specifically, it relates to the use of NOS inhibitors, particularly selective neuronal NOS (N-NOS) inhibitors: (a) alone or in combination with another active agent for the treatment of psoriasis; (b) in combination with an antiinflammatory agent for the treatment of inflammatory disorders; (c) in combination with a narcotic analgesic (e.g., opiates such as morphine or demerol) for the treatment of pain; (d) in combination with a serotonin-1D (5HT.sub.1D) agonist (e.g., eletriptan or sumatriptan) for the treatment of migraine, cluster or other vascular headaches; (e) alone or in combination with other active agents for the enhancement of cognition; and (f) alone or in combination with other active agents for the treatment of sleep disorders such as apnea, narcolepsy and insomnia. There are three known isoforms of NOS--an inducible form (I-NOS) and two constitutive forms referred to as, respectively, neuronal NOS (N-NOS) and endothelial NOS (E-NOS). Each
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of these enzymes carries out the conversion of arginine to citrulline while producing a molecule of nitric oxide (NO) in response to various stimuli. It is believed that excess nitric oxide (NO) production by NOS plays a role in the pathology of a number of disorders and conditions in mammals. For example, NO produced by I-NOS is thought to play a role in diseases that involve systemic hypotension such as toxic shock and therapy with certain cytokines. It has been shown that cancer patients treated with cytokines such as interleukin 1 (IL-1), interleukin 2 (IL-2) or tumor necrosis factor (TNF) suffer cytokine-induced shock and hypotension due to NO produced from macrophages, i.e., inducible NOS (I-NOS), see Chemical & Engineering News, December 20, p. 33, (1993). I-NOS inhibitors can reverse this. It is also believed that INOS plays a role in the pathology of diseases of the central nervous system such as ischemia. For example, inhibition of I-NOS has been shown to ameliorate cerebral ischemic damage in rats, see Am. J. Physiol., 268, p. R286 (1995)). Suppression of adjuvant induced arthritis by selective inhibition of I-NOS is reported in Eur. J. Pharmacol., 273, p. 15-24 (1995). NO produced by N-NOS is thought to play a role in diseases such as cerebral ischemia, pain, and opiate tolerance. For example, inhibition of N-NOS decreases infarct volume after proximal middle cerebral artery occlusion in the rat, see J. Cerebr. Blood Flow Metab., 14, p. 924-929 (1994). N-NOS inhibition has also been shown to be effective in antinociception, as evidenced by activity in the late phase of the formalin-induced hindpaw licking and acetic acid-induced abdominal constriction assays, see Br. J. Pharmacol., 110, p. 219-224 (1993). In addition, subcutaneous injection of Freund's adjuvant in the rat induces an increase in NOSpositive neurons in the spinal cord that is manifested in increased sensitivity to pain, which can be treated with NOS inhibitors, see Japanese Journal of Pharmacology, 75, p. 327-335 (1997). Finally, opioid withdrawal in rodents has been reported to be reduced by N-NOS inhibition, see Neuropsychopharmacol., 13, p. 269-293 (1995). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Polymorphs of N-methyl-N-(3-{3-[2- thienylcarbonyl]-pyrazol-[1,5-alpha]- pyrimidin7-yl}phenyl)acetamide and compositions and methods related thereto Inventor(s): O'Donnell, Patrick B.; (San Diego, CA), Thiele, William J.; (San Diego, CA) Correspondence: Seed Intellectual Property Law Group Pllc; 701 Fifth Ave; Suite 6300; Seattle; WA; 98104-7092; US Patent Application Number: 20020107256 Date filed: October 16, 2001 Abstract: Polymorphs of N-methyl-N-(3-{3-[2-thienylcarbonyl]-pyrazol-[1,5-.alpha.]-pyrimidin-7-yl}phenyl)acetamide (Compound 1), and use of the same as a sedativehypnotic, anxiolytic, anticonvulsant, and skeletal muscle relaxant agent. Processes for making the same, as well as related compositions and methods are also disclosed, particularly with regard to treatment of insomnia. A polymorph Form I possessing exception physical and heat stability is provided. A polymorph Form II 1 Excerpt(s): This application claims the benefit of U.S. patent application Ser. No. 09/421,620 filed Oct. 19, 1999, which application was converted to U.S. Provisional Application for Patent No. 60/(awaiting) by petition on August, 2000, and of U.S. patent application Ser. No. 09/389,524, filed Sep. 2, 1999 which application was converted to U.S. Provisional Application for Patent No. 60/(awaiting) by petition on August, 2000. This invention is directed to polymorphs of N-methyl-N-(3{3-[2-thie- nylcarbonyl]pyrazol-[1,5-.alpha.]-pyrimidin-7-yl}phenyl)acetamide having activity over a wide range
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of indications, and particularly useful for the treatment of insomnia, and to related processes, compositions and methods. The term "insomnia" is used to describe all conditions related to the perception of inadequate or non-restful sleep by the patient (Dement, International Pharmacopsychiatry 17:3-38, 1982). Insomnia is the most frequent complaint, being reported by 32% of the adult population surveyed in the Los Angeles area (Bixler et al, Amer. Journal of Psychiatry 136:1257-1262, 1979), and 13% of the population surveyed in San Marino, Italy (Lugaresi et al., Psychiatric Annals 17:446453, 1987). Fully 45% of the surveyed adult population of Alachua County, Fla., reported trouble getting to sleep or staying asleep (Karacan et al., Social Science and Medicine 10:239-244, 1976). The prevalence of insomnia has also been shown to be related to the age and sex of the individuals, being higher in older individuals and in females. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Process for the production of N-[3-(3-cyanopyrazolo[1,5-a] pyrimidin-7-yl) phenyl]-Nethylacetamide (zaleplon) Inventor(s): Feher, Erika; (Debrecen, HU), Korodi, Ferenc; (Debrecen, HU), Magyar, Erika; (Debrecen, HU) Correspondence: Kenyon & Kenyon; One Broadway; New York; NY; 10004; US Patent Application Number: 20030040522 Date filed: June 12, 2002 Abstract: The present invention provides a process for the production of N-[3-(3cyanopyrazolo[1,5-a]pyrimidin-7-yl)phenyl]-N-ethylacetamide (zaleplon), an active ingredient that is approved for the treatment of insomnia. The process involves reacting N-[3-[3-(dimethylamino)-1-oxo-2-p- ropenyl]phenyl]-N-ethylacetamide or a salt thereof with 3-amino-4-cyanopyrazole or a salt thereof under acidic conditions in a reaction medium comprising a mixture of water and a water-miscible organic compound. Excerpt(s): This application claims the benefit of provisional application Serial No. 60/297,635, filed Jun. 12, 2001. The present invention relates to an improved process for producing N-[3-(3-cyanopyrazolo[1,5-a]pyrimidin-7-yl)phenyl]-N-ethylacetamide. Zaleplon, whose systematic chemical name is N-[3-(3-cyanopyrazolo[1- ,5-a]pyrimidin7-yl)phenyl]-N-ethylacetamide, possesses anxiolytic, antiepileptic, sedative and hypnotic properties. It is approved by the U.S. Food and Drug Administration for shortterm treatment of insomnia. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Standardized extracts of scutellaria lateriflora Inventor(s): Hoffmann, David Ludwig; (Santa Rosa, CA), Wolfson, Philip E.; (San Anselmo, CA) Correspondence: Jean Barish; 711 - 27th Avenue; San Francisco; CA; 94121; US Patent Application Number: 20030054050 Date filed: September 17, 2002 Abstract: The present invention relates to an improved extract of Scutellaria lateriflora, a method of preparing the same, and a pharmaceutical composition prepared from the present extract suitable for treating anxiety, insomnia, convulsions, muscle tension and
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spasm, and related manifestations and disorders in humans and other mammals. The invention also relates to an improved method of treating anxiety, insomnia, convulsions, muscle tension and spasm, and related manifestations and disorders in humans and other mammals by administering the improved extract of Scutellaria lateriflora. Excerpt(s): This application claims the benefit of U.S. Provisional Patent Application Serial No. 60/323,048, filed Sep. 17, 2001, entitled "Process and Total Phenol Standardization for Blue Skullcap (Scutellaria lateriflora)". The present invention is related to novel standardized extracts of Scutellaria lateriflora; methods for preparing the same; compositions containing these standardized extracts; and the treatment of anxiety, insomnia, convulsions, muscle tension and spasm, and related manifestations and disorders in humans and other mammals through the administration of compositions containing these standardized extracts. Anxiety is one of the most frequent psychological problems that humans experience. It is estimated that anxiety related psychiatric disorders affect over 13% of the population each year in the United States. The cost of this individual suffering and the social burden of anxiety are significant. Effective treatment of anxiety and related disorders can significantly alleviate the suffering and distress associated with such disorders. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Substance with sedative effect Inventor(s): Krylov, Boris Vladimirovich; (Pavlovo, RU), Shchegolev, Boris Fedorovich; (St-Petersburg, RU) Correspondence: Boris Leschinsky; P.O. Box 72; Waldwick; NJ; 07463; US Patent Application Number: 20030181516 Date filed: March 14, 2003 Abstract: A substance with sedative effect comprises a therapeutically effective amount of a gamma-pyrone such as comenic acid, meconic acid, chelidonic acid, and alike in a pharmaceutically acceptable carrier. When administered at a daily dosage of between 5 and 200 mg of active ingredient per kilogram of a body weight of a patient, the substance can be used to treat various neurotic disorders such as insomnia, anxiety, neurosis, depression as well as withdrawal symptoms for drug addiction patients, especially for patients addicted to opioid-based drugs. The substance can be delivered in a number of ways of systemic administration of a pharmaceutical agent including oral, parenteral, transdermal, and transmucosal administration. For drug addicted patients, the preferred method of administration involves a subcutaneous implant providing a continuous release of an active ingredient at an effective daily rate over the entire treatment period ranging from 5 to 30 days, and preferably from 13 to 20 days. Excerpt(s): This application claims foreign priority benefits of a Russian Patent Application No. 2002107079/14 filed Mar. 19, 2002 with the same title. The present invention relates generally to pharmaceutical compounds and methods for their use to cause sedative and analgesic effects in animals and humans. More specifically, the invention relates to the use of gamma-pyrones in pharmaceutically acceptable forms for the treatment of various neurotic disorders. For the purposes of this description, the term "neurotic disorder" includes among others such conditions as anxiety, pain, insomnia, depression, neurosis as well as pain and other symptoms associated with treatment of chemical and drug abuse patients. All of these conditions involve the
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neurons of the central nervous system. Sedative compounds known in the art are a chemically varied group of compositions of natural and synthetic origin that predominantly have a tranquilizing effect on the central nervous system. Different sedatives produce different physiological effects. Understanding of these effects is helpful in selectively treating various disorders. This mechanism of action is not always entirely clear but it is believed that sedative drugs in general are intended to cause selective suppression of subcortical (limbus) and cortical brain structures, which regulate emotions. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Synthesis of substituted pyrazolopyrimidines Inventor(s): Gross, Raymond S.; (Poway, CA), Wilcoxen, Keith M.; (San Diego, CA) Correspondence: Seed Intellectual Property Law Group Pllc; 701 Fifth Ave; Suite 6300; Seattle; WA; 98104-7092; US Patent Application Number: 20030004346 Date filed: March 27, 2002 Abstract: Methods of making substituted pyrazolopyrimidines generally and, more particularly, N-methyl-N-(3-{3-[2-thienylcarbonyl]-pyrazol-[1,5-.alpha.]-- pyrimidin-7yl}phenyl)acetamide. Such compounds have utility over a wide range of indications, including treatmn(t of insomnia. In the practice of the present invention, improved techniques which do not require use and/or isolation of the pyrazole intermediate are disclosed, as well as improved techniques for making the reaction intermediates themselves. Such techniques offer significant advantages, including enhanced efficiency, particularly in the context of large scale manufacture. Excerpt(s): This application claims the benefit of U.S. Provisional Application Nos. 60/148,313 filed Aug. 10, 1999 and 60/148,314 filed Aug. 10, 1999. This invention is directed to the synthesis of substituted pyrazolopyrimidines, which compounds have utility over a wide range of indications including treatment of insomnia. wherein R.sub.2, R.sub.3, R.sub.5, R.sub.6 and R.sub.7 are as defined in U.S. Pat. No. 4,521,422 (but under a different numbering scheme for the various R groups). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Use of benzopyranols to treat neurological disorders Inventor(s): Evans, John Morris; (Roydon, GB), Parsons, Andrew; (Arlesey, GB), Thompson, Mervyn; (Harlow, GB), Upton, Neil; (Harlow, GB) Correspondence: Glaxosmithkline; Corporate Intellectual Property - Uw2220; P.O. Box 1539; King OF Prussia; PA; 19406-0939; US Patent Application Number: 20020010209 Date filed: July 19, 2001 Abstract: Benzopyran derivatives and analogs are disclosed as useful for the treatment and/or prophylaxis of degenerative diseases such as Huntingdon's chorea, schizophrenia, neurological deficits associated with AIDS, sleep disorders (including circadian rhythm disorders, insomnia and narcolepsy), tics (e.g. Giles de la Tourette's syndrome), traumatic brain injury, tinnitus, neuralgia, especially trigeminal neuralgia,
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neuropathic pain, dental pain, cancer pain, inappropriate neuronal activity resulting in neurodysthesias in diseases such as diabetes, MS and motor neurone disease, ataxias, muscular rigidity (spasticity), temporomandibular joint dysfunction. Excerpt(s): This invention relates to a novel method of treatment. EP-A-0 126 311 discloses substituted benzopyran compounds having blood pressure lowering activity, including 6-acetyl-trans-4-(4-fluoroben- zoylamino)-3,4-dihydro-2,2-dimethyl-2H-1benzopyran-3-ol. Also EP-A-0 376 524, EP-A-0 205 292, EP-A-0 250 077, EP-A-0 093 535, EP-A-0 150 202, EP-A-0 076 075 and WO/89/05808 (Beecham Group plc) describe certain benzopyran derivatives which possess anti-hypertensive activity. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
Keeping Current In order to stay informed about patents and patent applications dealing with insomnia, 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 “insomnia” (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 insomnia. You can also use this procedure to view pending patent applications concerning insomnia. 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 INSOMNIA Overview This chapter provides bibliographic book references relating to insomnia. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on insomnia include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.
Book Summaries: Federal Agencies The Combined Health Information Database collects various book abstracts from a variety of healthcare institutions and federal agencies. To access these summaries, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. You will need to use the “Detailed Search” option. To find book summaries, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer. For the format option, select “Monograph/Book.” Now type “insomnia” (or synonyms) into the “For these words:” box. You should check back periodically with this database which is updated every three months. The following is a typical result when searching for books on insomnia: •
Tinnitus Handbook Source: San Diego, CA: Singular Publishing Group. 2000. 477 p. Contact: Available from Singular-Thomson Learning. P.O. Box 6904, Florence, KY 41022. (800) 477-3692. Fax (606) 647-5963. Website: www.singpub.com. PRICE: $65.95 plus shipping and handling. ISBN: 1565939220. Summary: This audiology textbook offers clinicians and recent graduates information on tinnitus (ringing or other sounds in the ears). The author includes information on tinnitus, insomnia, physiological mechanisms and neural models, medical and surgical evaluation and management, tinnitus and children, and an historical perspective on tinnitus. Specific topics include psychoacoustical measurement, spontaneous otoacoustic emissions and tinnitus, and the psychological measurement of tinnitus. The author reviews the options for therapy and treatment, including hearing aids, maskers, cognitive behavior modification, electrical stimulation, habituation therapy, counseling,
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and biofeedback. Additional chapters address the medicolegal issues of tinnitus and resources including the American Tinnitus Association and self help groups. Each chapter includes a list of references and the textbook concludes with a subject index. •
Management of Challenging Behaviors in Dementia Source: Baltimore, MD: Health Professions Press. 2000. 236 p. Contact: Available from Health Professions Press. PO Box 10624, Baltimore, MD 212850624. (888) 337-8808; FAX: (410) 337-8539. Internet: http://www.healthpropress.com. PRICE: $34.00. ISBN: 1878812467. Item number: 2467. Summary: This book is a guide to the management of challenging behaviors in dementia. It presents a systematic approach to reducing or eliminating challenging behaviors by addressing their underlying causes within four critical areas: caregiving practices, physical environment, social environment, medical treatment. It describes intervention strategies for cognitive and physical impairments, mood disorders, delusions and hallucinations, anxiety, spatial disorientation, resistance to care, food refusal, insomnia, apathy, agitation, and inability to initiate activity. The use of nonpharmacological approaches is emphasized and illustrated with case reports. The book includes a glossary and index.
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Carer's Companion: A Winslow Guide to Caring at Home Source: Bicester, England: Winslow Press Limited. 1994. 165 p. Contact: Available from Speech Bin, Inc. 1766 Twentieth Avenue, Vero Beach, FL 32960. (407) 770-0007. PRICE: $21.50 plus 10 percent shipping and handling. ISBN: 0863881319. Summary: This book is designed to give practical advice on how to cope with caring for someone who has dementia, depression, or the after- effects of a stroke. Suggestions are made that are designed to assist caregivers in the day-to-day living with the person they care for and the feelings that may from time to time overwhelm them. Chapters discuss maintaining caregiver health; using respite care; having financial and emotional support; arranging legal matters; and dealing with typical problems such as forgetfulness, insomnia, aggression, incontinence, and sexual problems.
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Live Now, Age Later: Proven Ways to Slow Down the Clock Source: New York, NY: Warner Books. 1999. 398 p. Contact: Available from Warner Books. 1271 Avenue of the Americas, New York, NY 10020. (800) 759-0190. E-mail:
[email protected]. Website: www.twbookmark.com. PRICE: $7.99 plus shipping and handling. Summary: This book offers practical strategies and healthy living advice for people who want to slow down their own aging process. The book is written in casual language with an emphasis on explaining medical and health issues for the general public. Twenty chapters cover Alzheimer's disease, cancer, constipation, depression, hearing loss, heart attacks, erectile dysfunction (impotence), insomnia, libido, menopause, osteoarthritis, osteoporosis, prostate enlargement, aging skin, stroke, diminished taste and smell, tinnitus, tooth loss, and loss of vision (macular degeneration, cataracts, glaucoma). Each chapter reviews the topic in question, risk factors, the type of symptoms that can be expected, diagnostic tests that are used to confirm the problem, treatment options, and prognosis. A final section offers general health guidelines that focus on the importance of positive thinking and healthy lifestyle choices. A subject index concludes the book.
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Psychosocial Intervention in Long-Term Care: An Advanced Guide Source: New York, NY: The Haworth Press, Inc. 1997. 219 p. Contact: Haworth press, Inc. 10 Alice Street, Binghamton, NY 13904-1580. (800) 4296784; (607) 722-5857; FAX (800) 895-0582. PRICE: $49.95 (hardcover); $29.95 (softcover). ISBN: 0789001144 (hardcover); 0789001896 (softcover). Summary: This book on psychosocial intervention in long-term care (LTC) is designed to be an advanced guide for social workers, nurses, and other professionals with some basic knowledge of psychosocial assessment and intervention. The information may be useful to staff caring for people with Alzheimer's disease and other dementias who exhibit psychosocial and behavior problems. It provides a brief overview of the history and future psychosocial services in LTC, and then discusses the psychosocial needs of LTC residents, the assessment of mental disorders in LTC, and the administration and interpretation of the Geriatric Depression Scale and the Mini-Mental State Examination. The next chapters focus on intervention, including counseling and psychotherapy, behavioral assessments and interventions, interventions for specific psychosocial and behavioral problems (delusions, hallucinations, agitation, sexual problems, depression, and insomnia), and psychiatric medications. Other chapters discuss administrative issues, legal and ethical issues, and the prevention of staff burnout. Appendices contain additional materials to help LTC facilities prepare for a Health Care Financing Administration survey.
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Handbook of Clinical Behavior Therapy With the Elderly Client Source: New York, NY: Plenum Press. 1991. 510 p. Contact: Available from Plenum Press. 233 Spring Street, New York, NY 10013. ISBN: 0306437562. Summary: This four-part book presents a comprehensive explanation of the relatively new field of behavioral gerontology. The first part contains an overview of the field of behavioral gerontology, including its distinguishing characteristics and a review of the behavioral intervention research, categorized by problem area. The second part discusses the influence of medication, nutrition, residential placement, social support, and cognitive impairment on treatment, all factors essential to the design of an intervention program. The third part covers treatment applications for individuals presenting with a variety of problems, including anxiety, social skills deficits, datingmarital-sexual dilemmas, depression, memory impairment, insomnia, institutionalization, health, and pain problems. The fourth part addresses ways of intervening in the health care system: staff training, family care, health service providers, and community services. Two chapters specifically address cognitive/memory impairment, and behavioral programs for families of dependent elderly. Chapter 6 describes reversible and irreversible disorders and gives an overview of assessment tests. Chapter 11 discusses a behavioral problem solving approach for caregivers to reduce caregiver burden.
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Over-50 Guide to Psychiatric Medications Source: Washington, DC: American Psychiatric Association, Council on Aging. 1989. 148 p. Contact: American Psychiatric Association. 1400 K Street, NW, Washington, DC 20005. (202) 682-6000 or FAX (202) 682-6114. PRICE: $10.00. ISBN: 0890421277.
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Summary: This guide describes general considerations for the use of medications in treating mental illness in older adults. The guide details the use of medications in treating mood disorders, anxiety disorders, insomnia and other sleep disorders, disturbed thinking and behavior, and Alzheimer's disease (AD) and other forms of dementia. AD is the most common case of dementia. Dementia affects the function of many parts of the brain, including the areas involved in emotions and control over behavior. Thus, patients may experience not only intellectual decline but also disturbances of mood and behavior. Physicians may use some of the various psychoactive medicines to help relieve the emotional and behavioral disturbances that may occur in patients with dementia. •
Integrating Traditional, Experimental & Complementary Therapies for Living Long & Living Well: First International Conference on Traditional & Complementary Therapies in the Prevention & Treat. of Contact: Institute for Learning Mastery, PO Box 314, Baltimore, MD, 21203, (410) 3667373. US Library of Congress, Congressional Research Service, 1st St & Independence Ave SE, Washington, DC, 20540, (202) 707-5700. Summary: This sound recording of proceedings from Changing the Odds; Living Long and Living Well, The First International Conference on Traditional and Complementary Therapies in the Prevention and Treatment of AIDS, held February 17-19, 1989, in Washington, D.C., features Dr. Charles Steinberg talking about progress in the treatment of Acquired immunodeficiency syndrome (AIDS), and combining traditional and alternative therapies into the most effective treatment. He opens his talk by saying that a survey showed that while 50 percent of the doctors responding would eat cookies prepared for them by a leukemia patient, only 23 percent would eat cookies prepared by a Person with AIDS (PWA). These attitudes, he said, are what need shifted. He says doctors and patients need to think of Human immunodeficiency virus (HIV) infection as a chronic, manageable disease, and that thinking needs to go beyond just survival and cure of a particular opportunistic infection; patients need to stop facing their dying, and start facing their living. Steinberg tells doctors and PWA's not to place too much faith in the results of tests. He then outlines available drug therapies, including azidothymidine (AZT), pentamidine, DDI, Compound Q, and acyclovir. He goes on to discuss other treatments, such as Chinese medicine, which includes acupuncture, nutrition, and herbal remedies. This treatment can often balance out the energy in the body and relieve symptoms like itching and headaches. Steinberg explains nutritional approaches to maximizing health and enhancing vitality and immunity. This creates a less favorable environment for some opportunistic infections. Steinberg moves on to talk about the vital role of physical exercise in mental, social, and physical health. His talk emphasizes the importance of support -- not just formal support groups, but also a network of people to talk to and call on. He discusses the importance of meditation and spiritual factors in soothing the mind. Steinberg tells several stories about patients from his own practice, and goes on to discuss society's attitudes toward PWA's. He gives advice on dealing with various symptoms and problems, such as insomnia and lack of appetite. Emphasizing empowerment, he says that taking control of one's own life and one's own tr.
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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 “insomnia” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “insomnia” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “insomnia” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •
5-HTP : The Natural Way to Overcome Depression, Obesity, and Insomnia by Michael Murray (Author); ISBN: 0553379461; http://www.amazon.com/exec/obidos/ASIN/0553379461/icongroupinterna
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A Good Night's Sleep: A Step-By-Step Program for Overcoming Insomnia and Other Sleep Problems by Jerrold S. Maxmen; ISBN: 0393014371; http://www.amazon.com/exec/obidos/ASIN/0393014371/icongroupinterna
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Anyone for Insomnia?: A Playful Look at Sleeplessness by Richard Willard Armour; ISBN: 0912800690; http://www.amazon.com/exec/obidos/ASIN/0912800690/icongroupinterna
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Behavioral Treatment for Persistent Insomnia by Patricia Lacks (1987); ISBN: 0080343171; http://www.amazon.com/exec/obidos/ASIN/0080343171/icongroupinterna
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Behavioral Treatment for Persistent Insomnia (1987); ISBN: 0205144004; http://www.amazon.com/exec/obidos/ASIN/0205144004/icongroupinterna
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Body of Insomnia and Other Poems by Ludwig Zellar, A. F. Moritz (Translator) (2002); ISBN: 1896860036; http://www.amazon.com/exec/obidos/ASIN/1896860036/icongroupinterna
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Case Studies in Insomnia (Critical Issues in Psychiatry) by Peter J. Hauri (Editor) (1991); ISBN: 0306437910; http://www.amazon.com/exec/obidos/ASIN/0306437910/icongroupinterna
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Chinese Medicine Cures Insomnia (Chinese Medicine Cures) by Bob Flaws, Sylvia Schroer (Editor); ISBN: 0572025688; http://www.amazon.com/exec/obidos/ASIN/0572025688/icongroupinterna
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Clinical Handbook of Insomnia by Hrayr P. Attarian (Editor) (2004); ISBN: 158829272X; http://www.amazon.com/exec/obidos/ASIN/158829272X/icongroupinterna
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Commercial Perspectives: Sleep Disorders - Insomnia, Narcolepsy & Restless Leg Syndrome [DOWNLOAD: PDF] by Datamonitor (Author); ISBN: B0000UF8CU; http://www.amazon.com/exec/obidos/ASIN/B0000UF8CU/icongroupinterna
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Creative Insomnia by Douglas Colligan; ISBN: 0531099016; http://www.amazon.com/exec/obidos/ASIN/0531099016/icongroupinterna
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Cure by Crying: How to Cure Your Own, Depression, Nervousness, Headaches, Violent Temper, Insomnia, Marital Problems, Addictions by Uncovering Your Repressed memories by Thomas A. Stone (1997); ISBN: 0964767406; http://www.amazon.com/exec/obidos/ASIN/0964767406/icongroupinterna
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Curing Insomnia Naturally with Chinese Medicine by Bob Flaws; ISBN: 0936185864; http://www.amazon.com/exec/obidos/ASIN/0936185864/icongroupinterna
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Desperately Seeking Snoozin' : The Insomnia Cure from Awake to Zzzzz by John Wiedman (1999); ISBN: 0966418956; http://www.amazon.com/exec/obidos/ASIN/0966418956/icongroupinterna
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Diseases Explained: Insomnia Wall Chart by Lexi-Comp; ISBN: 1930598599; http://www.amazon.com/exec/obidos/ASIN/1930598599/icongroupinterna
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Eliminate Insomnia with America's Foremost Hypnotist by Mesmer (2000); ISBN: 0968850723; http://www.amazon.com/exec/obidos/ASIN/0968850723/icongroupinterna
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Evaluation and Treatment of Insomnia by Anthony Kales, Joyce D. Kales (Photographer); ISBN: 0195034341; http://www.amazon.com/exec/obidos/ASIN/0195034341/icongroupinterna
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Everybody's Guide to Natural Sleep: A Drug-Free Approach to Overcoming Insomnia and Other Sleep Disorders by Philip Goldberg, Daniel Kaufman (Contributor); ISBN: 0874775701; http://www.amazon.com/exec/obidos/ASIN/0874775701/icongroupinterna
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Finger Acupressure: Treatment for Many Common Ailments from Migraine to Insomnia by Using Finger Massage on Acupuncture Points by Pedro Chan; ISBN: 0843103442; http://www.amazon.com/exec/obidos/ASIN/0843103442/icongroupinterna
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Freedom from Insomnia: The Natural Way to Solve Sleep Problems by Alexander Stalmatski (2001); ISBN: 1856263789; http://www.amazon.com/exec/obidos/ASIN/1856263789/icongroupinterna
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Get a Good Night's Sleep: Understand Your Sleeplessness-And Banish It Forever! (Life's Little Keys - Self-Help Strategies for a Healthier, Happier You) by Frank Joe Bruno; ISBN: 0028613066; http://www.amazon.com/exec/obidos/ASIN/0028613066/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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Herbs for a Good Night's Sleep: Herbal Approaches to Relieving Insomnia Safely and Effectively (Keats Good Herb Guide Series) by David Hoffmann; ISBN: 0879837934; http://www.amazon.com/exec/obidos/ASIN/0879837934/icongroupinterna
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Herbs for the Mind: What Science Tells Us about Nature's Remedies for Depression, Stress, Memory Loss, and Insomnia by Jonathan R. T. Davidson, Kathryn M. Connor; ISBN: 1572304766; http://www.amazon.com/exec/obidos/ASIN/1572304766/icongroupinterna
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Holistic Sleep: Beating Insomnia With Commonsense, Medical, and New Age Techniques by Francis B., Md. Buda (2000); ISBN: 0806521058; http://www.amazon.com/exec/obidos/ASIN/0806521058/icongroupinterna
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How to Sleep Better: A Drug-Free Program for Overcoming Insomnia by Thomas J., Coates; ISBN: 0134338545; http://www.amazon.com/exec/obidos/ASIN/0134338545/icongroupinterna
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How to Sleep Like a Bear: Putting Insomnia to Bed by Dara Boland (2001); ISBN: 0890879753; http://www.amazon.com/exec/obidos/ASIN/0890879753/icongroupinterna
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Insomnia - Doctor I Can't Sleep by Adrian Williams (1996); ISBN: 1899308091; http://www.amazon.com/exec/obidos/ASIN/1899308091/icongroupinterna
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Insomnia (Sound Techniques for Healing) by Robert Friedman, Kelly Howell; ISBN: 1881451208; http://www.amazon.com/exec/obidos/ASIN/1881451208/icongroupinterna
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Insomnia (Talk to the Doctor) by Charles F. III Reynolds; ISBN: 0886467640; http://www.amazon.com/exec/obidos/ASIN/0886467640/icongroupinterna
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Insomnia : Principles and Management by Martin P. Szuba (Editor), et al (2003); ISBN: 0521010764; http://www.amazon.com/exec/obidos/ASIN/0521010764/icongroupinterna
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Insomnia and Nerve Strain; Oral Insomnia and Nerve Strain; Oral Infections and Systemic Disease by H. Cotton H. Upson, S.H. Shakman; ISBN: 1892506114; http://www.amazon.com/exec/obidos/ASIN/1892506114/icongroupinterna
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Insomnia and Other Sleeping Problems by Peter Lambley; ISBN: 1558171851; http://www.amazon.com/exec/obidos/ASIN/1558171851/icongroupinterna
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Insomnia Control/Adult Affirmations (Psy-Tech Alpha Tones) by William Hewitt, et al; ISBN: 0875423450; http://www.amazon.com/exec/obidos/ASIN/0875423450/icongroupinterna
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Insomnia Cures: Sleep Hygiene Practice Makes Permanent by Barry Krakow M.D., Barry James Krakow (2002); ISBN: 097158690X; http://www.amazon.com/exec/obidos/ASIN/097158690X/icongroupinterna
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Insomnia Journal: Between Dusk and Dawn by Laurie A. Baum (Author) (1997); ISBN: 1556706642; http://www.amazon.com/exec/obidos/ASIN/1556706642/icongroupinterna
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Insomnia Plus.: The Answer to Sleeplessness by Willa V. Bowles, Carl G. Wirth; ISBN: 0962571601; http://www.amazon.com/exec/obidos/ASIN/0962571601/icongroupinterna
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Insomnia: A Clinical Guide to Assessment and Treatment by Charles M. Morin (Editor), Colin A. Espie (Editor) (2003); ISBN: 0306477505; http://www.amazon.com/exec/obidos/ASIN/0306477505/icongroupinterna
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Insomnia: A Guide for Medical Practitioners by A. N. Nicholson; ISBN: 0852007639; http://www.amazon.com/exec/obidos/ASIN/0852007639/icongroupinterna
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Insomnia: A Subliminal Persuasion/Self-Hypnosis by Barry Konicov; ISBN: 087082340X; http://www.amazon.com/exec/obidos/ASIN/087082340X/icongroupinterna
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Insomnia: A Subliminal/Self-Hypnosis Program [ABRIDGED] by Barrie Konicov (2003); ISBN: 0870829696; http://www.amazon.com/exec/obidos/ASIN/0870829696/icongroupinterna
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Insomnia: Don't Lose Sleep over It Finding the Help You Need by Linda K. Devries (2000); ISBN: 0877881847; http://www.amazon.com/exec/obidos/ASIN/0877881847/icongroupinterna
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Insomnia: God's Night School by Connie Soth; ISBN: 0800753054; http://www.amazon.com/exec/obidos/ASIN/0800753054/icongroupinterna
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Insomnia: Or, the Devil at Large by Henry, Miller; ISBN: 0385002556; http://www.amazon.com/exec/obidos/ASIN/0385002556/icongroupinterna
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Insomnia: Psychological Assessment and Management by Charles M. Morin; ISBN: 1572301201; http://www.amazon.com/exec/obidos/ASIN/1572301201/icongroupinterna
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Insomnia; the guide for troubled sleepers by Gay Gaer Luce (Author), Julius Segal (Author); ISBN: B00005W71S; http://www.amazon.com/exec/obidos/ASIN/B00005W71S/icongroupinterna
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Insomnia? 41 Simple Tips for Getting to Sleep [DOWNLOAD: ADOBE READER] by Mick Winter (Editor) (2003); ISBN: B0000C7HTZ; http://www.amazon.com/exec/obidos/ASIN/B0000C7HTZ/icongroupinterna
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Insomniacs of the World, Goodnight: A Bedside Book, by Random House [1974]Rc New York; ISBN: 0394489985; http://www.amazon.com/exec/obidos/ASIN/0394489985/icongroupinterna
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Insomnia's Box by John Frazier (2002); ISBN: 0595237509; http://www.amazon.com/exec/obidos/ASIN/0595237509/icongroupinterna
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Is Your House Making You Overweight, Sick, or Tired?: Household Causes Including Improper Electricity of Weight Gain, Stress, Insomnia and Ill Health, by Margaret Rouse Shontz (2003); ISBN: 0972324372; http://www.amazon.com/exec/obidos/ASIN/0972324372/icongroupinterna
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Kava: Nature's Answer to Stress, Anxiety, and Insomnia by Hyla Cass, Terrence McNally (1998); ISBN: 0761516670; http://www.amazon.com/exec/obidos/ASIN/0761516670/icongroupinterna
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Natural Relief from Headaches, Insomnia & Stress: Safe, Effective Herbel Remedies by David Hoffmann; ISBN: 0879839821; http://www.amazon.com/exec/obidos/ASIN/0879839821/icongroupinterna
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Natural Sleep: How to Beat Insomnia Without Drugs by Anthea Courtenay; ISBN: 0722519478; http://www.amazon.com/exec/obidos/ASIN/0722519478/icongroupinterna
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New York Insomnia & Other Poems by Philip Callow (1988); ISBN: 0947612025; http://www.amazon.com/exec/obidos/ASIN/0947612025/icongroupinterna
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Outwitting Insomnia: Overcoming Sleeplessness and Getting the Rest You Need with Classic and Cutting-Edge Remedies That Really Work by Ellen Mohr Catalano (Author) (2003); ISBN: 1592281230; http://www.amazon.com/exec/obidos/ASIN/1592281230/icongroupinterna
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Psychic Symbolism of Headaches, Insomnia, and the Upset Stomach by Manly P. Hall; ISBN: 0893143456; http://www.amazon.com/exec/obidos/ASIN/0893143456/icongroupinterna
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Relief from Insomnia by Charles M. Morin (1996); ISBN: 0385427530; http://www.amazon.com/exec/obidos/ASIN/0385427530/icongroupinterna
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Relief from Insomnia: Getting the Sleep of Your Dreams by Charles M., PhD Morin (1996); ISBN: 0385477066; http://www.amazon.com/exec/obidos/ASIN/0385477066/icongroupinterna
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Restful Sleep: The Complete Mind/Body Program for Overcoming Insomnia by Deepak Chopra (1996); ISBN: 0517884577; http://www.amazon.com/exec/obidos/ASIN/0517884577/icongroupinterna
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Ronensha No Fumin: (Insomnia of Aged People) (1991); ISBN: 4431706089; http://www.amazon.com/exec/obidos/ASIN/4431706089/icongroupinterna
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Say Good Night to Insomnia: The Only Natural Treatment Scientifically Proven to Conquer Insomnia by Gregg D. Jacobs (1999); ISBN: 0756762855; http://www.amazon.com/exec/obidos/ASIN/0756762855/icongroupinterna
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Say Goodnight to Insomnia by Gregg D. Jacobs, Herbert Benson (Introduction); ISBN: 0805055487; http://www.amazon.com/exec/obidos/ASIN/0805055487/icongroupinterna
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Sleep and Sleeplessness in Advanced Age (Advances in Sleep Research, V. 5) by Rene Spiegel; ISBN: 0893351040; http://www.amazon.com/exec/obidos/ASIN/0893351040/icongroupinterna
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Sleep at Last or How Not to Be an Insomniac by Paul James; ISBN: 0831749008; http://www.amazon.com/exec/obidos/ASIN/0831749008/icongroupinterna
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Sleep Disorders and Insomnia in the Elderly (Facts and Research in Gerontology, Vol 7 1993) by J. L. Albarede (Editor), et al (1993); ISBN: 0826181716; http://www.amazon.com/exec/obidos/ASIN/0826181716/icongroupinterna
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Sleep Disorders Sourcebook: Basic Consumer Health Information About Sleep and Its Disorders, Including Insomnia, Sleepwalking, Sleep Apmea, Restless Leg Syndrome, and Narcolepsy; by Jenifer Swanson (Editor), Jennifer Swanson (1999); ISBN: 0780802349; http://www.amazon.com/exec/obidos/ASIN/0780802349/icongroupinterna
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Sleep Disorders: Insomnia and Narcolepsy by Henry Kellerman; ISBN: 0876302649; http://www.amazon.com/exec/obidos/ASIN/0876302649/icongroupinterna
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Sleep Right in Five Nights: A Clear and Effective Guide for Conquering Insomnia by James Perl (1995); ISBN: 0688140645; http://www.amazon.com/exec/obidos/ASIN/0688140645/icongroupinterna
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Sleep Though Insomnia by Krs Edstrom; ISBN: 1886198039; http://www.amazon.com/exec/obidos/ASIN/1886198039/icongroupinterna
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Stress and Relaxation: Self-Help Ways to Cope With Stress and Relieve Nervous Tension, Ulcers, Insomnia, Migraine, and High Blood Pressure by Jane. Madders; ISBN: 0668046805; http://www.amazon.com/exec/obidos/ASIN/0668046805/icongroupinterna
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Super Strength Freedom from Insomnia/Overcoming Worry by Robert Griswold (1993); ISBN: 1558483128; http://www.amazon.com/exec/obidos/ASIN/1558483128/icongroupinterna
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The 2002 Official Patient's Sourcebook on Insomnia by Icon Health Publications, et al (2002); ISBN: 059783153X; http://www.amazon.com/exec/obidos/ASIN/059783153X/icongroupinterna
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The Great Anxiety Escape: A Revolutionary Program to Escape Anxiety, Insomnia, Depression and Drug Dependency by Max Ricketts, et al (1990); ISBN: 0962620505; http://www.amazon.com/exec/obidos/ASIN/0962620505/icongroupinterna
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The Infinite Mind: Insomnia by Lichtenstein Creative Media Inc; ISBN: 1888064153; http://www.amazon.com/exec/obidos/ASIN/1888064153/icongroupinterna
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The Insomnia Pack: Includes Almond Oil and Lavender and Peppermint Essential Oils (Cures for Modern Times) by Journey Editions (1997); ISBN: 188520342X; http://www.amazon.com/exec/obidos/ASIN/188520342X/icongroupinterna
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The Management of Anxiety and Insomnia: a Report by the National Medical Advisory Committee by J.D. Gilleghan (1994); ISBN: 0114952744; http://www.amazon.com/exec/obidos/ASIN/0114952744/icongroupinterna
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The Psychological Treatment of Insomnia (Wiley Series in Clinical Psychology) by Colin A. Espie; ISBN: 0471923699; http://www.amazon.com/exec/obidos/ASIN/0471923699/icongroupinterna
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Time-Life Alternative Remedies for Common Ailments: How to Treat, Arthritis, Back Problems, Chronic Fatigue, Headaches, Insomnia, Sinusitis-- And over 40 More Common Health Conditions by Time-Life Books (Editor); ISBN: 073701105X; http://www.amazon.com/exec/obidos/ASIN/073701105X/icongroupinterna
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Treatment of Late-Life Insomnia by Kenneth L. Lichstein (Editor), Charles M. Morin (Editor) (2000); ISBN: 0761915079; http://www.amazon.com/exec/obidos/ASIN/0761915079/icongroupinterna
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Understanding Sleeplessness: Perspectives on Insomnia by David N., Md. Neubauer, Paul R. McHugh (2003); ISBN: 0801873266; http://www.amazon.com/exec/obidos/ASIN/0801873266/icongroupinterna
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Yawn: Bedtime Reading for Insomniacs by Ellen Sue Stern (Compiler); ISBN: 1580081614; http://www.amazon.com/exec/obidos/ASIN/1580081614/icongroupinterna
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Yoga Therapy: Overcoming Insomnia by Peter Van Houten, et al (2004); ISBN: 1565891740; http://www.amazon.com/exec/obidos/ASIN/1565891740/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 “insomnia” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:11 •
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A treatise on hysteria and epilepsy, with some concluding observations on epileptic insomnia. Author: Corning, James Leonard,; Year: 1958; Detroit, Davis, 1888
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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All you need to know about insomnia, sleep, and dreams. Author: Bauer, W. W. (William Waldo),; Year: 1956; New York [Essandess Special Editions] 1967
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Children's sleep; a series of studies on the influence of motion pictures; normal age, sex, and seasonal variations in motility; experimental insomnia; the effects of coffee; and the visual flicker limens of children [by] Samuel Renshaw. Vernon L. Miller. [and] Dorothy P. Marquis. Author: Renshaw, Samuel,; Year: 1969; New York, The Macmillan company, 1933
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Congestive neurasthenia, or insomnia and nerve depression. Author: Whittle, Edward George.; Year: 1935; London, Lewis, 1889
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Conquer insomnia. Author: Pai, Mangalore Narasimha.; Year: 1935; [London] Souvenir Press [1965]
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Finger acupuncture; treatment for many common ailments from migraine to insomnia by using finger massage on acupuncture points. Author: Chan, Pedro.; Year: 1707; Los Angeles, Price [c1974]
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I can't sleep; three silly chapters on insomnia. Author: Morrison, George W.; Year: 1969; New York, Crowell [c1948]
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Insomnia: correlates and treatment considerations: January 1977 through November 1983: 424 citations in English Author: Balter, Mitchell B.; Year: 1963; [Bethesda, Md.]: U.S. Dept. of Health and Human Services, Public Health Service, National Institutes of Health, 1983
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Insomnia and its relation to dreams. Author: Gilman, Leonard,; Year: 1909; Philadelphia, Lippincott [c1958]
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Insomnia and its therapeutics. Author: Macfarlane, Alexander William,; Year: 1935; London, Lewis, 1890
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Insomnia and nerve strain, by Henry S. Upson. with skiagraphic illustrations. Author: Upson, Henry S. (Henry Swift),; Year: 1962; New York and London, G. P. Putnam's sons, 1908
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Insomnia and other disturbances of sleep, by Emanuel Miller. Author: Miller, Emanuel,; Year: 1965; London, J. Bale, sons; Danielsson, ltd., 1935
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Insomnia, the guide for troubled sleepers [by] Gay Gaer Luce and Julius Segal. Author: Luce, Gay Gaer.; Year: 1956; Garden City, N. Y., Doubleday, 1969
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Insomnia; an effective treatment. Author: Damrau, Frederic,; Year: 1914; [St. Louis, Dios Chemical Co., c1935]
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Insomnia; an outline for the practitioner, by H. Crichton-Miller. Author: CrichtonMiller, Hugh,; Year: 1887; London, E. Arnold; co., 1930
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Insomnia; and other disorders of sleep. By Henry M. Lyman. Author: Lyman, Henry Munson,; Year: 1930; Chicago, W. T. Keener, 1885
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Insomnia; how to combat it, by Joseph Collins. Author: Collins, Joseph,; Year: 1930; New York, London, D. Appleton and company, 1930
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Insomnia; its causes and cure. Author: Sawyer, James,; Year: 1958; Birmingham, Cornish, 1904
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Insomnia; its causes and treatment. Author: Millet, John Alfred Parsons,; Year: 1967; New York, Greenberg [c1938]
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Integration of behavioral and relaxation approaches into the treatment of chronic pain and insomnia: January 1985 through July 1995: 1147 citations Author: Glock, Martha.; Year: 1983; Bethesda, Md. (8600 Rockville Pike): U.S. Dept. of Health and Human Services, Public Health Service, National Institutes of Health, National Library of
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Medicine, Reference Section; Pittsburgh, PA: Sold by the Supt. of Docs., U.S. G.P.O., 1995 •
Movable kidney; a cause of insanity, headache, neurasthenia, insomnia, mental failure and other disorders of the nervous system. A cause also of dilatation of the stomach. Author: Suckling, Cornelius William.; Year: 1970; London, Lewis, 1905
•
Nervous and mental diseases. A manual for students and practitioners. With an appendix on insomnia. By Joseph Darwin Nagel. Author: Nagel, Joseph Darwin,; Year: 1888; Philadelphia and New York, Lea; Febiger [1914]
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Shakespeare's insomnia and the causes thereof. Author: Head, Franklin Harvey,; Year: 1974; Boston, Houghton, Miffin, 1887
•
Sleep and the sleepless; simple rules for overcoming insomnia, by Joseph Collins. Author: Collins, Joseph,; Year: 1983; New York, Sturgis; Walton company, 1912
•
Sleeping pills, insomnia, and medical practice: report of a study Author: Institute of Medicine (U.S.). Division of Mental Health and Behavioral Medicine.; Year: 1938; Washington: National Academy of Sciences, 1979; ISBN: 0309028817 http://www.amazon.com/exec/obidos/ASIN/0309028817/icongroupinterna
Chapters on Insomnia In order to find chapters that specifically relate to insomnia, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and insomnia 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 “insomnia” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on insomnia: •
Tinnitus and Insomnia Source: in Tyler, R.S., ed. Tinnitus Handbook. San Diego, CA: Singular Publishing Group. 2000. p. 59-84. Contact: Available from Singular-Thomson Learning. P.O. Box 6904, Florence, KY 41022. (800) 477-3692. Fax (606) 647-5963. Website: www.singpub.com. PRICE: $65.95 plus shipping and handling. ISBN: 1565939220. Summary: Sleep disturbance is a frequent complaint of people with tinnitus; indeed some patients regard it as an integral element of the experience of tinnitus. This chapter on tinnitus and insomnia is from an audiology textbook that offers clinicians and recent graduates information on tinnitus (ringing or other sounds in the ears). In the chapter, the author discusses the prevalence and definitions of insomnia (a range of sleep related complaints, including sleep of insufficient duration, of poor quality or effectiveness); the nature and function of sleep; the characteristics of insomnia; the extent of the problem of tinnitus related insomnia; assessment methods, including clinical interview, sleep diaries, assessment of mood, sleep questionnaires, polysomnographic recordings, and other behavioral assessments; models of insomnia; the mechanisms of tinnitus related insomnia; the management of insomnia, including medication, behavioral treatment, relaxation therapy, stimulus control techniques, paradoxical intention, sleep restriction, and approaches to the management of intrusive cognition (thoughts); and the management of tinnitus related insomnia. The author concludes that the high
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prevalence of sleep disorders in populations with tinnitus, and vice versa, requires that researchers and clinicians in the tinnitus field have a responsibility to investigate tinnitus related insomnia more carefully and to seek solutions to the problem. 1 figure. 73 references. •
Effects of Insomnia on Tinnitus Severity: A Follow-Up Study Source: in Hazell, J., ed. Proceedings of the Sixth International Tinnitus Seminar. London, England: Tinnitus and Hyperacusis Centre. 1999. p. 271-276. Contact: Available from Tinnitus and Hyperacusis Centre. 32 Devonshire Place, London, W1N 1PE, United Kingdom. Fax 44 + (0) 207 486 2218. E-mail:
[email protected]. Website: www.tinnitus.org. PRICE: Contact publisher for price. ISBN: 0953695700. Also available on CD-ROM. Summary: This article on the interplay between insomnia and tinnitus severity is from a lengthy document that reprints the proceedings of the Sixth International Tinnitus Seminar, held in Cambridge, United Kingdom, in September 1999 and hosted by the British Society of Audiology. In this article, the authors describe their study undertaken to investigate the effects of insomnia on tinnitus severity and to determine how this relationship may evolve with the passage of time. Questionnaires were mailed to patients prior to their initial appointment at the Oregon Health Sciences University Tinnitus Clinic between 1994 and 1997. These questionnaires requested information pertaining to insomnia, tinnitus severity, and loudness. During their initial appointment, patients received counseling, education, and reassurance about tinnitus; audiometric and tinnitus evaluations; and treatment recommendations. Follow up questionnaires were mailed to 350 patients one to four years (mean of 2.3 years) after their initial appointment at the Clinic. Questionnaires were returned by 174 patients (130 males, 44 females; mean age 55.9 years). Even though many of these patients improved in both sleep interference and tinnitus severity, a significant number (43 patients) reported on the follow up questionnaire that they continued to have difficulty sleeping. Reported loudness and severity of tinnitus were significantly greater for this group than for groups of patients who reported that they never or only sometimes have difficulty sleeping. The relationship between sleep disturbance and tinnitus severity became more pronounced with the passage of time. The authors conclude that their findings underscore the importance of identification and successful treatment of insomnia for patients with tinnitus. One appendix offers the follow up questionnaire used in the study. 6 tables. 18 references.
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CHAPTER 8. MULTIMEDIA ON INSOMNIA Overview In this chapter, we show you how to keep current on multimedia sources of information on insomnia. 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.
Video Recordings An excellent source of multimedia information on insomnia is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “insomnia” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find video productions, 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 “Videorecording (videotape, videocassette, etc.).” Type “insomnia” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on insomnia: •
Hypoglycemia Source: Los Angeles, CA: National Health Video, Inc. 1998. (videocassette). Contact: Available from National Health Video, Inc. 12021 Wilshire Blvd., Suite 550, Los Angeles, CA 90025. (800) 543-6803. Fax (310) 477-8198. E-mail:
[email protected]. PRICE: $89.00 plus shipping and handling. Order number 273. Summary: This videotape provides people who have diabetes with information on hypoglycemia. Although the Diabetes Control and Complications Trial demonstrated that intensive glucose control reduces the complications of diabetes, it found that tight control poses a higher risk of hypoglycemia. From the video, patients learn the causes, symptoms, and prevention of hypoglycemia, as well as its treatment. Causes include inconsistent insulin effects. Symptoms depend on the severity of the episode and include shaking, sweating, hunger, lightheadedness, insomnia, confusion, and irritability. Situations that affect medication needs are exercise, food, and stress. Other topics are the variation between individuals, special challenges during pregnancy, times
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when hypoglycemia is most likely, dangers of hypoglycemia awareness, and the importance of testing and quick action. For a mild episode, people can selftreat by ingesting a serving of food containing 15 grams of carbohydrate, 2 large lumps of sugar, or 2 to 5 glucose tablets, or they can drink orange juice or milk. For more severe cases, someone else's assistance is needed. Prevention involves following one's meal plan, eating at the same time each day, measuring food portions, testing blood glucose regularly, taking insulin on a regular schedule, and testing blood glucose before and after exercise.
Bibliography: Multimedia on Insomnia 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 insomnia (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 insomnia: •
Insomnia [videorecording] Source: Time Life Medical; produced in association with Sonalysts Studios; Year: 1996; Format: Videorecording; New York, NY: Patient Education Media, c1996
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Insomnia [videorecording] Source: [presented by] Marshfield Clinic, Saint Joseph's Hospital [and] Marshfield Research Foundation; Year: 1990; Format: Videorecording; Marshfield, WI: Marshfield Video Network, [1990]
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Insomnia and addiction [videorecording]: meeting the standard of care Source: Marshfield Clinic, Saint Joseph's Hospital; a presentation of the Marshfield Video Network; Year: 1995; Format: Videorecording; Marshfield, WI: Video Network, [1995]
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Insomnia, in search of Morpheus [videorecording] Source: Behavioral Sciences Media Laboratory, the Neuropsychiatric Institute, UCLA Center for the Health Sciences; Year: 1979; Format: Videorecording; [Berkeley, Calif.]: Regents of the University of California, c1979
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Practical management of insomnia [videorecording] Source: a co-production of Multimedia Communications and Physician Education and Development; Year: 2001; Format: Videorecording; Oakland, CA: Kaiser Foundation Health Plan, c2001
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Strategies for managing insomnia [videorecording] Source: American Academy of Family Physicians, American Academy of Sleep Medicine; Year: 1999; Format: Videorecording; Leawood, KS: American Academy of Family Physicians, c1999
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The behavioral and pharmacologic management of insomnia [videorecording] Source: Marshfield Clinic, Saint Joseph's Hospital; a presentation of the Marshfield Video Network; Year: 1993; Format: Videorecording; Marshfield, WI: The Clinic, [1993]
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CHAPTER 9. PERIODICALS AND NEWS ON INSOMNIA Overview In this chapter, we suggest a number of news sources and present various periodicals that cover insomnia.
News Services and Press Releases One of the simplest ways of tracking press releases on insomnia 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 “insomnia” (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 insomnia. 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 “insomnia” (or synonyms). The following was recently listed in this archive for insomnia: •
FDA extends review of Sepracor insomnia drug Source: Reuters Industry Breifing Date: November 13, 2003
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NICE backs cheapest drugs for insomnia Source: Reuters Industry Breifing Date: October 20, 2003
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Lundbeck lines up partner for insomnia drug Source: Reuters Industry Breifing Date: September 26, 2003
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Neurocrine says insomnia drug increases sleep time Source: Reuters Industry Breifing Date: September 25, 2003
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Sepracor insomnia drug clears phase III trial Source: Reuters Industry Breifing Date: May 21, 2003
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Neurocrine insomnia drug shows positive results Source: Reuters Industry Breifing Date: May 19, 2003
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Study finds insomnia may affect immune system Source: Reuters Health eLine Date: April 18, 2003
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Insomniacs more aggravated by daily stress Source: Reuters Health eLine Date: April 04, 2003
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FDA to review Sepracor's experimental insomnia therapy Source: Reuters Industry Breifing Date: April 02, 2003
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Pfizer forges insomnia drug deal with Neurocrine Source: Reuters Industry Breifing Date: December 19, 2002
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Neurocrine reports phase III efficacy for insomnia drug Source: Reuters Industry Breifing Date: November 14, 2002
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Relationship woes behind much insomnia: survey Source: Reuters Health eLine Date: November 01, 2002
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Up to half of Japanese plagued by insomnia: Kyodo Source: Reuters Health eLine Date: July 05, 2002
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Neurocrine gains patent, starts phase III trial of insomnia drug Source: Reuters Industry Breifing Date: June 04, 2002
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Half of chronically ill patients have insomnia Source: Reuters Health eLine Date: April 08, 2002
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Police officers' insomnia due to daily grind Source: Reuters Health eLine Date: April 01, 2002
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Neurocrine outlines phase III schedule for insomnia drug Source: Reuters Industry Breifing Date: March 19, 2002
Periodicals and News
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Pfizer starts phase I trial of Neurogen insomnia agent Source: Reuters Industry Breifing Date: March 11, 2002
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Many experience insomnia after September 11th Source: Reuters Health eLine Date: November 29, 2001
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Neurocrine launches phase III trial for potential insomnia drug Source: Reuters Industry Breifing Date: November 16, 2001
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Kava, valerian may fight stress-related insomnia Source: Reuters Health eLine Date: October 04, 2001
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Insomniacs have hyperactive stress system Source: Reuters Health eLine Date: August 16, 2001
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Neurocrine's insomnia agent performs well in phase II studies Source: Reuters Industry Breifing Date: July 17, 2001
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Insomnia is a strong predictor of relapse in alcoholics Source: Reuters Medical News Date: April 13, 2001
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Cognitive behavioral therapy a viable treatment option for insomnia Source: Reuters Medical News Date: April 12, 2001
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New behavioral therapy helps treat insomnia Source: Reuters Health eLine Date: April 10, 2001
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Cessation of medication misuse alleviates insomnia in migraine patients Source: Reuters Industry Breifing Date: February 01, 2001
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Lack of daylight may explain older people's insomnia Source: Reuters Health eLine Date: January 25, 2001
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High prevalence of insomnia found in Chinese wome Source: Reuters Medical News Date: January 22, 2001
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Lundbeck insomnia drug enters new trials Source: Reuters Industry Breifing Date: November 15, 2000
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Melatonin no cure for jet lag, but may fight insomnia Source: Reuters Health eLine Date: November 08, 2000
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Short-term zaleplon use effective in older patients with chronic insomnia Source: Reuters Industry Breifing Date: October 11, 2000
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Sepracor's insomnia treatment (S)-zopiclone set to begin phase III trials Source: Reuters Industry Breifing Date: August 29, 2000 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 “insomnia” (or synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests. Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “insomnia” (or synonyms). If you know the name of a company that is relevant to insomnia, 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 “insomnia” (or synonyms).
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Newsletter Articles Use the Combined Health Information Database, and limit your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter Article.” Type “insomnia” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months. The following is a typical result when searching for newsletter articles on insomnia: •
Sleep and Rheumatic Disease Source: Bulletin on the Rheumatic Diseases. 45(8):1-6; December 1996. Contact: Arthritis Foundation, 1330 West Peachtree Street, Atlanta, GA 30309. (404) 8727100. (404) 872-9559 (fax). Summary: This newsletter article for health professionals discusses the association between sleep disturbance and rheumatic disease. Clinical types of insomnia are described, and predisposing, precipitating, and perpetuating factors are identified. Disorders included in the main groups of sleep disturbances are highlighted. Statistics on the prevalence of rheumatic diseases are provided. Information on the comorbidity of sleep disturbances and rheumatologic disorders is presented. Recent clinical research demonstrates the frequent comorbidity of sleep disturbance, pains, fatigue, stress, and mood disturbance in individuals with rheumatic disease. Guidelines for assessing and treating patients with sleep disturbances are offered. Treatment of sleep disorders in rheumatic disease include nonpharmacologic interventions, such as maintenance of appropriate sleep hygiene, behavioral and psychological therapies, and pharmacologic interventions. Precautions for using hypnotics are presented. 36 references and 3 tables.
•
Prescribed Medications Source: Fibromyalgia Frontiers. 9(3): 17-22. 2001. Contact: Available from National Fibromyalgia Partnership, Inc. 140 Zinn Way, Linden, VA 22642-5609. (866) 725-4404 toll-free. Fax (540) 622-2998. E-mail:
[email protected]. Website: www.fmpartnership.org. Summary: This newsletter article provides health professionals and people who have fibromyalgia (FM) with information on prescription and nonprescription medications that can relieve pain and improve sleep and mood. Categories of drugs used in the treatment of fibromyalgia are analgesics, antiinflammatory drugs, antidepressant medications, muscle relaxants, sleep modifiers, antianxiety medicines, and other medicines used to treat chronic pain. Analgesics are pain killers and can include nonprescription medicines such as aspirin and acetaminophen or prescription strength pain pills such as narcotics, codeine, Vicodin, Darvocet, Oxycontin, and Percocet. Antiinflammatory medicines include aspirin, nonsteroidal antiinflammatory drugs, and corticosteroids. Antidepressant medications include tricyclics and selective serotonin reuptake inhibitors. Muscle relaxants can decrease pain in people who have FM and include Flexeril, Soma, Skelaxin, and Robaxin. Various medications can be used to treat insomnia, including benzodiazepines and hypnotic nonbenzodiazepines. Anxiety is a common problem in FM, but various medicines, including antidepressants and muscle relaxants, can treat it. Other medicines used to treat pain include antiseizure medicines,
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headache medications, and antibiotics. The article highlights the beneficial and adverse effects of each drug category. In addition, the article presents basic strategies regarding medication use and discusses the use of trigger point injections to manage pain.
Academic Periodicals covering Insomnia Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to insomnia. In addition to these sources, you can search for articles covering insomnia that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”
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CHAPTER 10. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.
U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for insomnia. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a nonprofit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI® Advice for the Patient® can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with insomnia. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.). The
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following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to insomnia: Benzodiazepines •
Systemic - U.S. Brands: Alprazolam Intensol; Ativan; Dalmane; Diastat; Diazepam Intensol; Dizac; Doral; Halcion; Klonopin; Librium; Lorazepam Intensol; Paxipam; ProSom; Restoril; Serax; Tranxene T-Tab; Tranxene-SD; Tranxene-SD Half Strength; Valium; Xanax http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202084.html
Caffeine •
Systemic - U.S. Brands: Cafcit; Caffedrine Caplets; Dexitac Stay Alert Stimulant; Enerjets; Keep Alert; Maximum Strength SnapBack Stimulant Powders; NoDoz Maximum Strength Caplets; Pep-Back; Quick Pep; Ultra Pep-Back; Vivarin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202105.html
Ethchlorvynol •
Systemic - U.S. Brands: Placidyl http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202230.html
Levodopa •
Systemic - U.S. Brands: Atamet; Larodopa; Sinemet; Sinemet CR http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202326.html
Nicotine •
Systemic - U.S. Brands: http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202326.html
•
Systemic - U.S. Brands: Habitrol; Nicorette; Nicotrol; Prostep http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202407.html
Zaleplon •
Systemic - U.S. Brands: Sonata http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500042.html
Zolpidem •
Systemic - U.S. Brands: Ambien http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202707.html
Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.
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Mosby’s Drug Consult™ Mosby’s Drug Consult™ database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/. PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee. If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.
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APPENDICES
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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.
NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute12: •
Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm
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National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/
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National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html
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National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25
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National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm
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National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm
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National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375
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National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/
12
These publications are typically written by one or more of the various NIH Institutes.
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•
National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm
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National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/
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National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm
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National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm
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National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/
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National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/
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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm
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National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html
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National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm
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National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm
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National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm
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National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html
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National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm
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Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp
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National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/
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National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp
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Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html
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Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm
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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.13 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:14 •
Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html
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HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html
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NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html
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Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/
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Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html
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Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html
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Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/
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Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html
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Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html
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Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html
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MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html
13
Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 14 See http://www.nlm.nih.gov/databases/databases.html.
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Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html
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Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html
The NLM Gateway15 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.16 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “insomnia” (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 6924 234 932 63 3 8156
HSTAT17 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.18 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.19 Simply search by “insomnia” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
15
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
16
The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 17 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 18 19
The HSTAT URL is http://hstat.nlm.nih.gov/.
Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.
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Coffee Break: Tutorials for Biologists20 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.21 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.22 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.
Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •
CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.
•
Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.
The Genome Project and Insomnia In the following section, we will discuss databases and references which relate to the Genome Project and insomnia. Online Mendelian Inheritance in Man (OMIM) The Online Mendelian Inheritance in Man (OMIM) database is a catalog of human genes and genetic disorders authored and edited by Dr. Victor A. McKusick and his colleagues at Johns Hopkins and elsewhere. OMIM was developed for the World Wide Web by the National Center for Biotechnology Information (NCBI).23 The database contains textual information, pictures, and reference information. It also contains copious links to NCBI’s Entrez database of MEDLINE articles and sequence information. 20 Adapted 21
from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.
The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 22 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process. 23 Adapted from http://www.ncbi.nlm.nih.gov/. Established in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information--all for the better understanding of molecular processes affecting human health and disease.
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To search the database, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type “insomnia” (or synonyms) into the search box, and click “Submit Search.” If too many results appear, you can narrow the search by adding the word “clinical.” Each report will have additional links to related research and databases. In particular, the option “Database Links” will search across technical databases that offer an abundance of information. The following is an example of the results you can obtain from the OMIM for insomnia: •
Familial Fatal Insomnia Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?600072 Genes and Disease (NCBI - Map)
The Genes and Disease database is produced by the National Center for Biotechnology Information of the National Library of Medicine at the National Institutes of Health. This Web site categorizes each disorder by system of the body. Go to http://www.ncbi.nlm.nih.gov/disease/, and browse the system pages to have a full view of important conditions linked to human genes. Since this site is regularly updated, you may wish to revisit it from time to time. The following systems and associated disorders are addressed: •
Cancer: Uncontrolled cell division. Examples: Breast and ovarian cancer, Burkitt lymphoma, chronic myeloid leukemia, colon cancer, lung cancer, malignant melanoma, multiple endocrine neoplasia, neurofibromatosis, p53 tumor suppressor, pancreatic cancer, prostate cancer, Ras oncogene, RB: retinoblastoma, von Hippel-Lindau syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Cancer.html
•
Immune System: Fights invaders. Examples: Asthma, autoimmune polyglandular syndrome, Crohn’s disease, DiGeorge syndrome, familial Mediterranean fever, immunodeficiency with Hyper-IgM, severe combined immunodeficiency. Web site: http://www.ncbi.nlm.nih.gov/disease/Immune.html
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Metabolism: Food and energy. Examples: Adreno-leukodystrophy, atherosclerosis, Best disease, Gaucher disease, glucose galactose malabsorption, gyrate atrophy, juvenile-onset diabetes, obesity, paroxysmal nocturnal hemoglobinuria, phenylketonuria, Refsum disease, Tangier disease, Tay-Sachs disease. Web site: http://www.ncbi.nlm.nih.gov/disease/Metabolism.html
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Muscle and Bone: Movement and growth. Examples: Duchenne muscular dystrophy, Ellis-van Creveld syndrome, Marfan syndrome, myotonic dystrophy, spinal muscular atrophy. Web site: http://www.ncbi.nlm.nih.gov/disease/Muscle.html
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Nervous System: Mind and body. Examples: Alzheimer disease, amyotrophic lateral sclerosis, Angelman syndrome, Charcot-Marie-Tooth disease, epilepsy, essential tremor, fragile X syndrome, Friedreich’s ataxia, Huntington disease, Niemann-Pick disease, Parkinson disease, Prader-Willi syndrome, Rett syndrome, spinocerebellar atrophy, Williams syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Brain.html
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•
Signals: Cellular messages. Examples: Ataxia telangiectasia, Cockayne syndrome, glaucoma, male-patterned baldness, SRY: sex determination, tuberous sclerosis, Waardenburg syndrome, Werner syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Signals.html
•
Transporters: Pumps and channels. Examples: Cystic fibrosis, deafness, diastrophic dysplasia, Hemophilia A, long-QT syndrome, Menkes syndrome, Pendred syndrome, polycystic kidney disease, sickle cell anemia, Wilson’s disease, Zellweger syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Transporters.html Entrez
Entrez is a search and retrieval system that integrates several linked databases at the National Center for Biotechnology Information (NCBI). These databases include nucleotide sequences, protein sequences, macromolecular structures, whole genomes, and MEDLINE through PubMed. Entrez provides access to the following databases: •
3D Domains: Domains from Entrez Structure, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo
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Books: Online books, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=books
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Genome: Complete genome assemblies, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Genome
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NCBI’s Protein Sequence Information Survey Results: Web site: http://www.ncbi.nlm.nih.gov/About/proteinsurvey/
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Nucleotide Sequence Database (Genbank): Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Nucleotide
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OMIM: Online Mendelian Inheritance in Man, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM
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PopSet: Population study data sets, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Popset
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ProbeSet: Gene Expression Omnibus (GEO), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo
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Protein Sequence Database: Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein
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PubMed: Biomedical literature (PubMed), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
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Structure: Three-dimensional macromolecular structures, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure
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Taxonomy: Organisms in GenBank, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Taxonomy
To access the Entrez system at the National Center for Biotechnology Information, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=genome, and then
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select the database that you would like to search. The databases available are listed in the drop box next to “Search.” Enter “insomnia” (or synonyms) into the search box and click “Go.” Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database24 This online resource has been developed to facilitate the identification and differentiation of syndromic entities. Special attention is given to the type of information that is usually limited or completely omitted in existing reference sources due to space limitations of the printed form. At http://www.nlm.nih.gov/mesh/jablonski/syndrome_toc/toc_a.html, you can search across syndromes using an alphabetical index. Search by keywords at http://www.nlm.nih.gov/mesh/jablonski/syndrome_db.html. The Genome Database25 Established at Johns Hopkins University in Baltimore, Maryland in 1990, the Genome Database (GDB) is the official central repository for genomic mapping data resulting from the Human Genome Initiative. In the spring of 1999, the Bioinformatics Supercomputing Centre (BiSC) at the Hospital for Sick Children in Toronto, Ontario assumed the management of GDB. The Human Genome Initiative is a worldwide research effort focusing on structural analysis of human DNA to determine the location and sequence of the estimated 100,000 human genes. In support of this project, GDB stores and curates data generated by researchers worldwide who are engaged in the mapping effort of the Human Genome Project (HGP). GDB’s mission is to provide scientists with an encyclopedia of the human genome which is continually revised and updated to reflect the current state of scientific knowledge. Although GDB has historically focused on gene mapping, its focus will broaden as the Genome Project moves from mapping to sequence, and finally, to functional analysis. To access the GDB, simply go to the following hyperlink: http://www.gdb.org/. Search “All Biological Data” by “Keyword.” Type “insomnia” (or synonyms) into the search box, and review the results. If more than one word is used in the search box, then separate each one with the word “and” or “or” (using “or” might be useful when using synonyms).
24
Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html. 25 Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html - mission.
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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 insomnia 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 insomnia. 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 insomnia. 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 “insomnia”:
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•
Other guides Alzheimer's Caregivers http://www.nlm.nih.gov/medlineplus/alzheimerscaregivers.html Alzheimer's Disease http://www.nlm.nih.gov/medlineplus/alzheimersdisease.html Bipolar Disorder http://www.nlm.nih.gov/medlineplus/bipolardisorder.html Club Drugs http://www.nlm.nih.gov/medlineplus/clubdrugs.html Disasters and Emergency Preparedness http://www.nlm.nih.gov/medlineplus/disastersandemergencypreparedness.html Herbal Medicine http://www.nlm.nih.gov/medlineplus/herbalmedicine.html Sleep Apnea http://www.nlm.nih.gov/medlineplus/sleepapnea.html Sleep Disorders http://www.nlm.nih.gov/medlineplus/sleepdisorders.html Sleep Disorders http://www.nlm.nih.gov/medlineplus/tutorials/sleepdisordersloader.html
Within the health topic page dedicated to insomnia, the following was listed: •
General/Overviews How Well Are You Sleeping? Source: Food and Drug Administration http://www.fda.gov/fdac/features/2002/602_sleep.html Interactive Sleep Quiz Source: National Heart, Lung, and Blood Institute http://www.nhlbisupport.com/sleep_scripts/tfSleepQuiz.pl Sleep Disorders http://www.nlm.nih.gov/medlineplus/tutorials/sleepdisordersloader.html
•
Treatment FDA Approves Xyrem for Cataplexy Attacks in Patients with Narcolepsy Source: Food and Drug Administration http://www.fda.gov/bbs/topics/ANSWERS/2002/ANS01157.html
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Alternative Therapy Melatonin Source: American Academy of Family Physicians http://familydoctor.org/handouts/258.html
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Questions and Answers about Valerian for Insomnia and Other Sleep Disorders Source: National Institutes of Health, Office of Dietary Supplements http://ods.od.nih.gov/factsheets/valerian.html •
Coping Helping Yourself to a Good Night's Sleep Source: National Sleep Foundation http://www.sleepfoundation.org/publications/goodnights.cfm Living with Narcolepsy Source: National Sleep Foundation http://www.sleepfoundation.org/publications/livingnarcolepsy.cfm Tips for Shift Workers: How to Eat, Sleep and Stay Fit When You Work Nights Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=HQ01388
•
Specific Conditions/Aspects Excessive Daytime Sleepiness Source: National Sleep Foundation http://www.sleepfoundation.org/epworth/quizfaq.cfm Hypersomnia Source: National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/health_and_medical/disorders/hypersomnia.htm Insomnia: How to Get a Good Night's Sleep Source: American Academy of Family Physicians http://familydoctor.org/healthfacts/110/ Kleine-Levin Syndrome Source: National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/health_and_medical/disorders/kleine_levin.htm Narcolepsy Source: National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/health_and_medical/disorders/narcolep_doc.htm Pain and Sleep Source: National Sleep Foundation http://www.sleepfoundation.org/publications/sleepandpain.cfm Public Split on Keeping Daylight Saving Time Year-Round Source: National Sleep Foundation http://www.sleepfoundation.org/PressArchives/yearround.cfm Sleep and the Traveler: How to Get the Most Out of Sleep When Traveling Source: National Sleep Foundation http://www.sleepfoundation.org/publications/travel.cfm Sleep Disorders (PDQ) Source: National Cancer Institute http://www.cancer.gov/cancerinfo/pdq/supportivecare/sleepdisorders/patient/
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What Is Bruxism? Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=DS00337 •
Children Nightmares and Night Terrors in Children Source: American Academy of Family Physicians http://familydoctor.org/handouts/566.html Sleep Problems: Parasomnia Source: Nemours Foundation http://kidshealth.org/parent/general/sleep/parasomnia.html Sleepwalking in Children Source: American Academy of Family Physicians http://familydoctor.org/handouts/160.html
•
From the National Institutes of Health Brain Basics: Understanding Sleep Source: National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/health_and_medical/pubs/understanding_sleep_brain _basic_.htm Good Night's Sleep? Merely a Dream for Millions Source: National Institutes of Health http://www.nih.gov/news/WordonHealth/jun98/story02.htm Star Sleeper Source: National Heart, Lung, and Blood Institute http://www.nhlbi.nih.gov/health/public/sleep/starslp/
•
Men Women & Sleep Source: National Sleep Foundation http://www.sleepfoundation.org/publications/women.cfm
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Organizations American Academy of Sleep Medicine http://www.aasmnet.org/ American Sleep Apnea Association http://www.sleepapnea.org/ National Center on Sleep Disorders Research http://www.nhlbi.nih.gov/about/ncsdr/index.htm National Heart, Lung, and Blood Institute http://www.nhlbi.nih.gov/ National Sleep Foundation http://www.sleepfoundation.org/
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Society for Neuroscience http://web.sfn.org/ •
Research “Power Nap” Prevents Burnout; Morning Sleep Perfects a Skill Source: National Institute of Mental Health http://www.nih.gov/news/pr/jul2002/nimh-02.htm Scientists Pinpoint Possible Cause for Debilitating Sleep Disorder Narcolepsy Source: National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/news_and_events/pressrelease_narcolepsy_082900.ht m?type=current
•
Statistics 2000 Omnibus Sleep in America Poll Source: National Sleep Foundation http://www.sleepfoundation.org/publications/2000poll.cfm Events of 9-11 Took Their Toll on American's Sleep, Particularly for Women Source: National Sleep Foundation http://www.sleepfoundation.org/whatsnew/crisis_poll.cfm How Common Are Sleep Problems in Children? Source: Nemours Foundation http://kidshealth.org/research/sleep_problems.html
•
Teenagers Pointers for Parents Source: National Sleep Foundation http://www.sleepfoundation.org/PressArchives/teens2.cfm Teens and Sleep Source: Nemours Foundation http://kidshealth.org/teen/your_body/take_care/sleep.html
•
Women Women & Sleep Source: National Sleep Foundation http://www.sleepfoundation.org/publications/women.cfm
You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search.
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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 insomnia. 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: •
Integration of Behavioral and Relaxation Approaches into the Treatment of Chronic Pain and Insomnia Source: Kensington, MD: NIH Consensus Program Information Center. October 1995. 38 p. Contact: Available from National Center for Complementary and Alternative Medicine Clearinghouse. P.O. Box 7923, Gaithersburg, MD 20898. (888) 644-6226; INTERNATIONAL PHONE: (301) 519-3153; TTY: (866) 464-3615; FAX: (866) 464-3616; EMAIL:
[email protected]. PRICE: Free. Publication Number: D031. Summary: This consensus statement provides physicians with a responsible assessment of the integration of behavioral and relaxation approaches into the treatment of chronic pain and insomnia. After the introduction, the report answers five major research questions: (1) What behavioral and relaxation approaches are used for conditions such as chronic pain and insomnia? (2) How successful are these approaches? (3) How do these approaches work? (4) Are there barriers to the appropriate integration of these approaches into health care? and (5) What are the significant issues for future research and applications? The report ends with a list of experts who served as members of the technology assessment panel and planning committee. 86 references. The National Guideline Clearinghouse™
The National Guideline Clearinghouse™ offers hundreds of evidence-based clinical practice guidelines published in the United States and other countries. You can search this site located at http://www.guideline.gov/ by using the keyword “insomnia” (or synonyms). The following was recently posted: •
Practice parameters for the evaluation of chronic insomnia Source: American Academy of Sleep Medicine - Professional Association; 2000; 5 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2276&nbr=1502&a mp;string=insomnia
•
Practice parameters for the nonpharmacologic treatment of chronic insomnia Source: American Academy of Sleep Medicine - Professional Association; 1999; 6 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2275&nbr=1501&a mp;string=insomnia
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Healthfinder™ Healthfinder™ is sponsored by the U.S. Department of Health and Human Services and offers links to hundreds of other sites that contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database: •
Diseases & Conditions: Internet Resources for Alternative Medicine Summary: Follow these links for information online related to alternative treatment options for this select group of diseases and disorders -- HIV/AIDS, asthma, cancer, epilepsy, headache, herpes, insomnia, Source: Educational Institution--Follow the Resource URL for More Information http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=3983
•
Facts About Insomnia Summary: This four-page brochure discusses insomnia -- inadequate or poor quality sleep because of difficulty falling asleep, and how it is treated. Source: National Center on Sleep Disorders Research, National Heart, Lung, and Blood Institute http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=410
•
Test Your Sleep I.Q. Summary: This true-false quiz tests what you know about sleep. Questions cover topics on snoring, narcolepsy, insomnia, restless legs syndrome, and other issues. Source: National Center on Sleep Disorders Research, National Heart, Lung, and Blood Institute http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=2384 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 insomnia. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html.
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Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/specific.htm
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Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/
•
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 insomnia. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with insomnia. 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 insomnia. 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 “insomnia” (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 “insomnia”. 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 “insomnia” (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 “insomnia” (or a synonym) into the search box, and click “Submit Query.”
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APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.
Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.26
Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.
Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of
26
Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.
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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)27: •
Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/
•
Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)
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Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm
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California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html
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California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html
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California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html
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California: Gateway Health Library (Sutter Gould Medical Foundation)
•
California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/
•
California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp
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California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html
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California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/
•
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/
27
Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.
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•
Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml
•
Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm
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Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html
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Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm
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Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp
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Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/
•
Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm
•
Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html
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Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/
•
Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm
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Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/
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Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/
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Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/
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Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm
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Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html
•
Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm
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Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/
•
Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/
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Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10
•
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
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Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp
•
Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/
•
Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html
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Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm
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Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp
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Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/
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Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html
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Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/
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Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm
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Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/
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Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html
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Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm
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Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330
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Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)
•
National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html
•
National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/
•
National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/
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Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm
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New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/
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New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm
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New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm
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New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/
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New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html
•
New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/
•
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
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Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html
•
Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html
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Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml
•
Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp
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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). The NIH suggests the following Web sites in the ADAM Medical Encyclopedia when searching for information on insomnia: •
Basic Guidelines for Insomnia Insomnia concerns Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002106.htm Sleeping difficulty Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003210.htm
•
Signs & Symptoms for Insomnia Anxiety Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003211.htm Apnea Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003069.htm Chest pain Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003079.htm
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Depression Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003213.htm Drowsiness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003208.htm Excitement Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003212.htm Fatigue Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003088.htm Heartburn Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003114.htm Hunger Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003134.htm Indigestion Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003260.htm Insomnia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003210.htm Memory impairment Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003257.htm Nightmares Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003209.htm Reduced energy level Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003088.htm Shortness of breath Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003075.htm Sleepy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003208.htm Snoring Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003207.htm Stress Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003211.htm Tiredness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003088.htm Wakefulness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003210.htm
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•
Diagnostics and Tests for Insomnia Cocaine Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003578.htm Polysomnogram Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003932.htm Polysomnography Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003932.htm PRA Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003698.htm Sleep studies Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003932.htm T3 Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003687.htm T4 Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003517.htm TSH Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003684.htm
•
Nutrition for Insomnia Caffeine Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002445.htm
•
Background Topics for Insomnia Acute Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002215.htm Alcohol use Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001944.htm Chronic Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002312.htm Exercise Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001941.htm Hypnotics Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002376.htm Physical examination Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002274.htm
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Smoking Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002032.htm Stimulants Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002308.htm Stressful situations Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001942.htm Teething Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002045.htm Traumatic event Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001924.htm
Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •
Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical
•
MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html
•
Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/
•
Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine
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INSOMNIA DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 5-alpha: Enzyme converting testosterone to dihydrotestosterone. [NIH] Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Ablation: The removal of an organ by surgery. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acetaminophen: Analgesic antipyretic derivative of acetanilide. It has weak antiinflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acetylcholinesterase: An enzyme that catalyzes the hydrolysis of acetylcholine to choline and acetate. In the CNS, this enzyme plays a role in the function of peripheral neuromuscular junctions. EC 3.1.1.7. [NIH] Acidosis: A pathologic condition resulting from accumulation of acid or depletion of the alkaline reserve (bicarbonate content) in the blood and body tissues, and characterized by an increase in hydrogen ion concentration. [EU] Acne: A disorder of the skin marked by inflammation of oil glands and hair glands. [NIH] Acoustic: Having to do with sound or hearing. [NIH] Action Potentials: The electric response of a nerve or muscle to its stimulation. [NIH] Acupuncture Analgesia: Analgesia produced by the insertion of acupuncture needles at certain points in the body. These activate the small myelinated nerve fibers in the muscle which transmit impulses to the spinal cord and then activate three centers - the spinal cord, midbrain and pituitary hypothalamus - to produce analgesia. [NIH] Acupuncture Points: Designated locations along nerves or organ meridians for inserting acupuncture needles. [NIH] Acupuncture Therapy: Treatment of disease by inserting needles along specific pathways or meridians. The placement varies with the disease being treated. Heat or moxibustion and acupressure may be used in conjunction. [NIH] Acyclovir: Functional analog of the nucleoside guanosine. It acts as an antimetabolite, especially in viruses. It is used as an antiviral agent, especially in herpes infections. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it
256 Insomnia
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] Adipocytes: Fat-storing cells found mostly in the abdominal cavity and subcutaneous tissue. Fat is usually stored in the form of tryglycerides. [NIH] Adjunctive Therapy: Another treatment used together with the primary treatment. Its purpose is to assist the primary treatment. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenal Medulla: The inner part of the adrenal gland; it synthesizes, stores and releases catecholamines. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adverse Effect: An unwanted side effect of treatment. [NIH] 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] Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [EU]
Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU]
Dictionary 257
Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]
Aggravation: An increasing in seriousness or severity; an act or circumstance that intensifies, or makes worse. [EU] Aggressiveness: The quality of being aggressive (= characterized by aggression; militant; enterprising; spreading with vigour; chemically active; variable and adaptable). [EU] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Agranulocytosis: A decrease in the number of granulocytes (basophils, eosinophils, and neutrophils). [NIH] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [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] Akathisia: 1. A condition of motor restlessness in which there is a feeling of muscular quivering, an urge to move about constantly, and an inability to sit still, a common extrapyramidal side effect of neuroleptic drugs. 2. An inability to sit down because of intense anxiety at the thought of doing so. [EU] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] Alertness: A state of readiness to detect and respond to certain specified small changes occurring at random intervals in the environment. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] 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 Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH]
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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] Alternative Splicing: A process whereby multiple protein isoforms are generated from a single gene. Alternative splicing involves the splicing together of nonconsecutive exons during the processing of some, but not all, transcripts of the gene. Thus a particular exon may be connected to any one of several alternative exons to form messenger RNA. The alternative forms produce proteins in which one part is common while the other part is different. [NIH] Amenorrhea: Absence of menstruation. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] 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] Amnesia: Lack or loss of memory; inability to remember past experiences. [EU] 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]
Amyloid: A general term for a variety of different proteins that accumulate as extracellular fibrils of 7-10 nm and have common structural features, including a beta-pleated sheet conformation and the ability to bind such dyes as Congo red and thioflavine (Kandel, Schwartz, and Jessel, Principles of Neural Science, 3rd ed). [NIH] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile
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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] Analeptic: A drug which acts as a restorative, such as caffeine, amphetamine, pentylenetetrazol, etc. [EU] 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] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Anesthetics: Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. [NIH] 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] Anode: Electrode held at a positive potential with respect to a cathode. [NIH] Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [NIH] Anorexia Nervosa: The chief symptoms are inability to eat, weight loss, and amenorrhea. [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] Anti-Anxiety Agents: Agents that alleviate anxiety, tension, and neurotic symptoms, promote sedation, and have a calming effect without affecting clarity of consciousness or neurologic conditions. Some are also effective as anticonvulsants, muscle relaxants, or anesthesia adjuvants. Adrenergic beta-antagonists are commonly used in the symptomatic treatment of anxiety but are not included here. [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]
Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH]
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Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticholinergic: An agent that blocks the parasympathetic nerves. Called also parasympatholytic. [EU] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Anticonvulsant: An agent that prevents or relieves convulsions. [EU] Antidepressant: A drug used to treat depression. [NIH] Antidepressive Agents: Mood-stimulating drugs used primarily in the treatment of affective disorders and related conditions. Several monoamine oxidase inhibitors are useful as antidepressants apparently as a long-term consequence of their modulation of catecholamine levels. The tricyclic compounds useful as antidepressive agents also appear to act through brain catecholamine systems. A third group (antidepressive agents, secondgeneration) is a diverse group of drugs including some that act specifically on serotonergic systems. [NIH] Antiemetic: An agent that prevents or alleviates nausea and vomiting. Also antinauseant. [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] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antimetabolite: A chemical that is very similar to one required in a normal biochemical reaction in cells. Antimetabolites can stop or slow down the reaction. [NIH] Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antipsychotic: Effective in the treatment of psychosis. Antipsychotic drugs (called also neuroleptic drugs and major tranquilizers) are a chemically diverse (including phenothiazines, thioxanthenes, butyrophenones, dibenzoxazepines, dibenzodiazepines, and diphenylbutylpiperidines) but pharmacologically similar class of drugs used to treat schizophrenic, paranoid, schizoaffective, and other psychotic disorders; acute delirium and dementia, and manic episodes (during induction of lithium therapy); to control the movement disorders associated with Huntington's chorea, Gilles de la Tourette's syndrome, and ballismus; and to treat intractable hiccups and severe nausea and vomiting. Antipsychotic agents bind to dopamine, histamine, muscarinic cholinergic, a-adrenergic, and serotonin receptors. Blockade of dopaminergic transmission in various areas is thought to be responsible for their major effects : antipsychotic action by blockade in the mesolimbic and mesocortical areas; extrapyramidal side effects (dystonia, akathisia, parkinsonism, and tardive dyskinesia) by blockade in the basal ganglia; and antiemetic effects by blockade in
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the chemoreceptor trigger zone of the medulla. Sedation and autonomic side effects (orthostatic hypotension, blurred vision, dry mouth, nasal congestion and constipation) are caused by blockade of histamine, cholinergic, and adrenergic receptors. [EU] Antipyretic: An agent that relieves or reduces fever. Called also antifebrile, antithermic and febrifuge. [EU] Antispasmodic: An agent that relieves spasm. [EU] Antitussive: An agent that relieves or prevents cough. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Anxiety Disorders: Disorders in which anxiety (persistent feelings of apprehension, tension, or uneasiness) is the predominant disturbance. [NIH] Anxiolytic: An anxiolytic or antianxiety agent. [EU] Apathy: Lack of feeling or emotion; indifference. [EU] Aperture: A natural hole of perforation, especially one in a bone. [NIH] Apnea: A transient absence of spontaneous respiration. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Approximate: Approximal [EU] 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] Aromatic: Having a spicy odour. [EU] Arrhythmia: Any variation from the normal rhythm or rate of the heart beat. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arteritis: Inflammation of an artery. [NIH] Articular: Of or pertaining to a joint. [EU] Arylsulfotransferase: A sulfotransferase that catalyzes the sulfation of a phenol in the presence of 3'-phosphoadenylylsulfate as sulfate donor to yield an aryl sulfate and adenosine 3',5'-bisphosphate. A number of aromatic compounds can act as acceptors; however, organic hydroxylamines are not substrates. Sulfate conjugation by this enzyme is a major pathway for the biotransformation of phenolic and catechol drugs as well as neurotransmitters. EC 2.8.2.1. [NIH] Asphyxia: A pathological condition caused by lack of oxygen, manifested in impending or
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actual cessation of life. [NIH] Aspirin: A drug that reduces pain, fever, inflammation, and blood clotting. Aspirin belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is also being studied in cancer prevention. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] 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 those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] Asymptomatic: Having no signs or symptoms of disease. [NIH] Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharnyx, larnyx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. [NIH] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Attenuated: Strain with weakened or reduced virulence. [NIH] Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Audiology: The study of hearing and hearing impairment. [NIH] Auditory: Pertaining to the sense of hearing. [EU] Aura: A subjective sensation or motor phenomenon that precedes and marks the of a paroxysmal attack, such as an epileptic attack on set. [EU] Auricular: Pertaining to an auricle or to the ear, and, formerly, to an atrium of the heart. [EU] Autoantibodies: Antibodies that react with self-antigens (autoantigens) of the organism that produced them. [NIH] Autodigestion: Autolysis; a condition found in disease of the stomach: the stomach wall is digested by the gastric juice. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autonomic: Self-controlling; functionally independent. [EU]
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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] Autosuggestion: Suggestion coming from the subject himself. [NIH] Baclofen: A GABA derivative that is a specific agonist at GABA-B receptors. It is used in the treatment of spasticity, especially that due to spinal cord damage. Its therapeutic effects result from actions at spinal and supraspinal sites, generally the reduction of excitatory transmission. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Barbiturate: A drug with sedative and hypnotic effects. Barbiturates have been used as sedatives and anesthetics, and they have been used to treat the convulsions associated with epilepsy. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [NIH] Basal metabolic rate: Represents the minimum energy expenditure required for the maintenance of vital functions; normally the amount of energy expended, measured in calories, per unit of time at rest; measured after 14-18 hours of rest. [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] Base Sequence: The sequence of purines and pyrimidines in nucleic acids and polynucleotides. It is also called nucleotide or nucleoside sequence. [NIH] Basophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. [NIH] Behavior Therapy: The application of modern theories of learning and conditioning in the treatment of behavior disorders. [NIH] Behavioral Symptoms: Observable manifestions of impaired psychological functioning.
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[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-pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Bewilderment: Impairment or loss of will power. [NIH] Bibliotherapy: A form of supportive psychotherapy in which the patient is given carefully selected material to read. [NIH] Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Biliary Tract: The gallbladder and its ducts. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Bioassay: Determination of the relative effective strength of a substance (as a vitamin, hormone, or drug) by comparing its effect on a test organism with that of a standard preparation. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] 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] Biological Assay: A method of measuring the effects of a biologically active substance using an intermediate in vivo or in vitro tissue or cell model under controlled conditions. It includes virulence studies in animal fetuses in utero, mouse convulsion bioassay of insulin, quantitation of tumor-initiator systems in mouse skin, calculation of potentiating effects of a hormonal factor in an isolated strip of contracting stomach muscle, etc. [NIH] Biological Clocks: The physiological mechanisms that govern the rhythmic occurrence of certain biochemical, physiological, and behavioral phenomena in plants and animals. [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]
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Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alteration may be either nonsynthetic (oxidation-reduction, hydrolysis) or synthetic (glucuronide formation, sulfate conjugation, acetylation, methylation). This also includes metabolic detoxication and clearance. [NIH] Bipolar Disorder: A major affective disorder marked by severe mood swings (manic or major depressive episodes) and a tendency to remission and recurrence. [NIH] Bladder: The organ that stores urine. [NIH] Bloating: Fullness or swelling in the abdomen that often occurs after meals. [NIH] Blood Cell Count: A count of the number of leukocytes and erythrocytes per unit volume in a sample of venous blood. A complete blood count (CBC) also includes measurement of the hemoglobin, hematocrit, and erythrocyte indices. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blood-Brain Barrier: Specialized non-fenestrated tightly-joined endothelial cells (tight junctions) that form a transport barrier for certain substances between the cerebral capillaries and the brain tissue. [NIH] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]
Body Composition: The relative amounts of various components in the body, such as percent body fat. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Body Mass Index: One of the anthropometric measures of body mass; it has the highest correlation with skinfold thickness or body density. [NIH] Body Regions: Anatomical areas of the body. [NIH] Bone Density: The amount of mineral per square centimeter of bone. This is the definition used in clinical practice. Actual bone density would be expressed in grams per milliliter. It is most frequently measured by photon absorptiometry or x-ray computed tomography. [NIH]
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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] Brachial: All the nerves from the arm are ripped from the spinal cord. [NIH] Brachial Artery: The continuation of the axillary artery; it branches into the radial and ulnar arteries. [NIH] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Brain Diseases: Pathologic conditions affecting the brain, which is composed of the intracranial components of the central nervous system. This includes (but is not limited to) the cerebral cortex; intracranial white matter; basal ganglia; thalamus; hypothalamus; brain stem; and cerebellum. [NIH] Brain Stem: The part of the brain that connects the cerebral hemispheres with the spinal cord. It consists of the mesencephalon, pons, and medulla oblongata. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]
Breakdown: A physical, metal, or nervous collapse. [NIH] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Bronchitis: Inflammation (swelling and reddening) of the bronchi. [NIH] Bronchoconstriction: Diminution of the caliber of a bronchus physiologically or as a result of pharmacological intervention. [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] Bullous: Pertaining to or characterized by bullae. [EU] Buprenorphine: A derivative of the opioid alkaloid thebaine that is a more potent and longer lasting analgesic than morphine. It appears to act as a partial agonist at mu and kappa opioid receptors and as an antagonist at delta receptors. The lack of delta-agonist activity has been suggested to account for the observation that buprenorphine tolerance may not develop with chronic use. [NIH] Bupropion: A unicyclic, aminoketone antidepressant. The mechanism of its therapeutic actions is not well understood, but it does appear to block dopamine uptake. The hydrochloride is available as an aid to smoking cessation treatment. [NIH] 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
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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] Calcification: Deposits of calcium in the tissues of the breast. Calcification in the breast can be seen on a mammogram, but cannot be detected by touch. There are two types of breast calcification, macrocalcification and microcalcification. Macrocalcifications are large deposits and are usually not related to cancer. Microcalcifications are specks of calcium that may be found in an area of rapidly dividing cells. Many microcalcifications clustered together may be a sign of cancer. [NIH] Calcitonin Gene-Related Peptide: Calcitonin gene-related peptide. A 37-amino acid peptide derived from the calcitonin gene. It occurs as a result of alternative processing of mRNA from the calcitonin gene. The neuropeptide is widely distributed in neural tissue of the brain, gut, perivascular nerves, and other tissue. The peptide produces multiple biological effects and has both circulatory and neurotransmitter modes of action. In particular, it is a potent endogenous vasodilator. [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] Candidiasis: Infection with a fungus of the genus Candida. It is usually a superficial infection of the moist cutaneous areas of the body, and is generally caused by C. albicans; it most commonly involves the skin (dermatocandidiasis), oral mucous membranes (thrush, def. 1), respiratory tract (bronchocandidiasis), and vagina (vaginitis). Rarely there is a systemic infection or endocarditis. Called also moniliasis, candidosis, oidiomycosis, and formerly blastodendriosis. [EU] Candidosis: An infection caused by an opportunistic yeasts that tends to proliferate and become pathologic when the environment is favorable and the host resistance is weakened. [NIH]
Canonical: A particular nucleotide sequence in which each position represents the base more often found when many actual sequences of a given class of genetic elements are compared. [NIH] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carcinogenic: Producing carcinoma. [EU]
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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] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]
Cardiac: Having to do with the heart. [NIH] Cardiorespiratory: Relating to the heart and lungs and their function. [EU] Cardiotonic: 1. Having a tonic effect on the heart. 2. An agent that has a tonic effect on the heart. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] 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] Carotid Sinus: The dilated portion of the common carotid artery at its bifurcation into external and internal carotids. It contains baroreceptors which, when stimulated, cause slowing of the heart, vasodilatation, and a fall in 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] Cataracts: In medicine, an opacity of the crystalline lens of the eye obstructing partially or totally its transmission of light. [NIH] Catechol: A chemical originally isolated from a type of mimosa tree. Catechol is used as an astringent, an antiseptic, and in photography, electroplating, and making other chemicals. It can also be man-made. [NIH] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Causal: Pertaining to a cause; directed against a cause. [EU] Celiac Disease: A disease characterized by intestinal malabsorption and precipitated by gluten-containing foods. The intestinal mucosa shows loss of villous structure. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell 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]
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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] Cellulose: A polysaccharide with glucose units linked as in cellobiose. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Central Nervous System Infections: Pathogenic infections of the brain, spinal cord, and meninges. DNA virus infections; RNA virus infections; bacterial infections; mycoplasma infections; Spirochaetales infections; fungal infections; protozoan infections; helminthiasis; and prion diseases may involve the central nervous system as a primary or secondary process. [NIH] Centrifugation: A method of separating organelles or large molecules that relies upon differential sedimentation through a preformed density gradient under the influence of a gravitational field generated in a centrifuge. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebellar Diseases: Diseases that affect the structure or function of the cerebellum. Cardinal manifestations of cerebellar dysfunction include dysmetria, gait ataxia, and muscle hypotonia. [NIH] Cerebellum: Part of the metencephalon that lies in the posterior cranial fossa behind the brain stem. It is concerned with the coordination of movement. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Arteries: The arteries supplying the cerebral cortex. [NIH] Cerebral Palsy: Refers to a motor disability caused by a brain dysfunction. [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] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Cervical Plexus: A network of nerve fibers originating in the upper four cervical spinal cord segments. The cervical plexus distributes cutaneous nerves to parts of the neck, shoulders, and back of the head, and motor fibers to muscles of the cervical spinal column, infrahyoid muscles, and the diaphragm. [NIH]
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Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] Chemoreceptor: A receptor adapted for excitation by chemical substances, e.g., olfactory and gustatory receptors, or a sense organ, as the carotid body or the aortic (supracardial) bodies, which is sensitive to chemical changes in the blood stream, especially reduced oxygen content, and reflexly increases both respiration and blood pressure. [EU] Chemotherapy: Treatment with anticancer drugs. [NIH] Chin: The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. [NIH] Chloride Channels: Cell membrane glycoproteins selective for chloride ions. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] 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] Cholinesterase Inhibitors: Drugs that inhibit cholinesterases. The neurotransmitter acetylcholine is rapidly hydrolyzed, and thereby inactivated, by cholinesterases. When cholinesterases are inhibited, the action of endogenously released acetylcholine at cholinergic synapses is potentiated. Cholinesterase inhibitors are widely used clinically for their potentiation of cholinergic inputs to the gastrointestinal tract and urinary bladder, the eye, and skeletal muscles; they are also used for their effects on the heart and the central nervous system. [NIH] Chorea: Involuntary, forcible, rapid, jerky movements that may be subtle or become confluent, markedly altering normal patterns of movement. Hypotonia and pendular reflexes are often associated. Conditions which feature recurrent or persistent episodes of chorea as a primary manifestation of disease are referred to as choreatic disorders. Chorea is also a frequent manifestation of basal ganglia diseases. [NIH] Choreatic Disorders: Acquired and hereditary conditions which feature chorea as a primary manifestation of the disease process. [NIH] Choroid: The thin, highly vascular membrane covering most of the posterior of the eye between the retina and sclera. [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] Chromium: A trace element that plays a role in glucose metabolism. It has the atomic symbol Cr, atomic number 24, and atomic weight 52. According to the Fourth Annual Report on Carcinogens (NTP85-002,1985), chromium and some of its compounds have been listed as known carcinogens. [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]
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Chronic Fatigue Syndrome: Fatigue caused by the combined effects of different types of prolonged fatigue. [NIH] Chronic Obstructive Pulmonary Disease: Collective term for chronic bronchitis and emphysema. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Chronobiology: The study of biological systems as affected by time. Aging, biological rhythms, and cyclic phenomena are included. Statistical, computer-aided mathematical procedures are used to describe, in mathematical terminology, various biological functions over time. [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] Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Clone: The term "clone" has acquired a new meaning. It is applied specifically to the bits of inserted foreign DNA in the hybrid molecules of the population. Each inserted segment originally resided in the DNA of a complex genome amid millions of other DNA segment. [NIH]
Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Coca: Any of several South American shrubs of the Erythroxylon genus (and family) that yield cocaine; the leaves are chewed with alum for CNS stimulation. [NIH] Cocaine: An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. [NIH] Cochlear: Of or pertaining to the cochlea. [EU] Cochlear Diseases: Diseases of the cochlea, the part of the inner ear that is concerned with hearing. [NIH] Codeine: An opioid analgesic related to morphine but with less potent analgesic properties
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and mild sedative effects. It also acts centrally to suppress cough. [NIH] Codon: A set of three nucleotides in a protein coding sequence that specifies individual amino acids or a termination signal (codon, terminator). Most codons are universal, but some organisms do not produce the transfer RNAs (RNA, transfer) complementary to all codons. These codons are referred to as unassigned codons (codons, nonsense). [NIH] Coenzymes: Substances that are necessary for the action or enhancement of action of an enzyme. Many vitamins are coenzymes. [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 behavior therapy: A system of psychotherapy based on the premise that distorted or dysfunctional thinking, which influences a person's mood or behavior, is common to all psychosocial problems. The focus of therapy is to identify the distorted thinking and to replace it with more rational, adaptive thoughts and beliefs. [NIH] Cognitive restructuring: A method of identifying and replacing fear-promoting, irrational beliefs with more realistic and functional ones. [NIH] Cognitive Therapy: A direct form of psychotherapy based on the interpretation of situations (cognitive structure of experiences) that determine how an individual feels and behaves. It is based on the premise that cognition, the process of acquiring knowledge and forming beliefs, is a primary determinant of mood and behavior. The therapy uses behavioral and verbal techniques to identify and correct negative thinking that is at the root of the aberrant behavior. [NIH] Colic: Paroxysms of pain. This condition usually occurs in the abdominal region but may occur in other body regions as well. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Colloidal: Of the nature of a colloid. [EU] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [NIH] Comet Assay: A genotoxicological technique for measuring DNA damage in an individual cell using single-cell gel electrophoresis. Cell DNA fragments assume a "comet with tail" formation on electrophoresis and are detected with an image analysis system. Alkaline assay conditions facilitate sensitive detection of single-strand damage. [NIH] Comorbidity: The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes
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immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complete remission: The disappearance of all signs of cancer. Also called a complete response. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] 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
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scan). [NIH] Concomitant: Accompanying; accessory; joined with another. [EU] Cone: One of the special retinal receptor elements which are presumed to be primarily concerned with perception of light and color stimuli when the eye is adapted to light. [NIH] Confounding: Extraneous variables resulting in outcome effects that obscure or exaggerate the "true" effect of an intervention. [NIH] Confusion: A mental state characterized by bewilderment, emotional disturbance, lack of clear thinking, and perceptual disorientation. [NIH] Congestion: Excessive or abnormal accumulation of blood in a part. [EU] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjugation: 1. The act of joining together or the state of being conjugated. 2. A sexual process seen in bacteria, ciliate protozoa, and certain fungi in which nuclear material is exchanged during the temporary fusion of two cells (conjugants). In bacterial genetics a form of sexual reproduction in which a donor bacterium (male) contributes some, or all, of its DNA (in the form of a replicated set) to a recipient (female) which then incorporates differing genetic information into its own chromosome by recombination and passes the recombined set on to its progeny by replication. In ciliate protozoa, two conjugants of separate mating types exchange micronuclear material and then separate, each now being a fertilized cell. In certain fungi, the process involves fusion of two gametes, resulting in union of their nuclei and formation of a zygote. 3. In chemistry, the joining together of two compounds to produce another compound, such as the combination of a toxic product with some substance in the body to form a detoxified product, which is then eliminated. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Consolidation: The healing process of a bone fracture. [NIH] Consolidation therapy: Chemotherapy treatments given after induction chemotherapy to further reduce the number of cancer cells. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constriction: The act of constricting. [NIH] Consultation: A deliberation between two or more physicians concerning the diagnosis and the proper method of treatment in a case. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Continuous infusion: The administration of a fluid into a blood vessel, usually over a prolonged period of time. [NIH] Continuum: An area over which the vegetation or animal population is of constantly changing composition so that homogeneous, separate communities cannot be distinguished. [NIH]
Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Control group: In a clinical trial, the group that does not receive the new treatment being
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studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Controlled clinical trial: A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]
Conventional therapy: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional treatment. [NIH] Conventional treatment: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional therapy. [NIH] Convulsion: A violent involuntary contraction or series of contractions of the voluntary muscles. [EU] Convulsive: Relating or referring to spasm; affected with spasm; characterized by a spasm or spasms. [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a 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] Corticosteroids: Hormones that have antitumor activity in lymphomas and lymphoid leukemias; in addition, corticosteroids (steroids) may be used for hormone replacement and for the management of some of the complications of cancer and its treatment. [NIH] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cortisone: A natural steroid hormone produced in the adrenal gland. It can also be made in the laboratory. Cortisone reduces swelling and can suppress immune responses. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] Cross Infection: Any infection which a patient contracts in a healthcare institution. [NIH]
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Cues: Signals for an action; that specific portion of a perceptual field or pattern of stimuli to which a subject has learned to respond. [NIH] Curare: Plant extracts from several species, including Strychnos toxifera, S. castelnaei, S. crevauxii, and Chondodendron tomentosum, that produce paralysis of skeletal muscle and are used adjunctively with general anesthesia. These extracts are toxic and must be used with the administration of artificial respiration. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] 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] Dangerous Behavior: Actions which have a high risk of being harmful or injurious to oneself or others. [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] Dehydration: The condition that results from excessive loss of body water. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Delirium: (DSM III-R) an acute, reversible organic mental disorder characterized by reduced ability to maintain attention to external stimuli and disorganized thinking as manifested by rambling, irrelevant, or incoherent speech; there are also a reduced level of consciousness, sensory misperceptions, disturbance of the sleep-wakefulness cycle and level of psychomotor activity, disorientation to time, place, or person, and memory impairment. Delirium may be caused by a large number of conditions resulting in derangement of cerebral metabolism, including systemic infection, poisoning, drug intoxication or withdrawal, seizures or head trauma, and metabolic disturbances such as hypoxia, hypoglycaemia, fluid, electrolyte, or acid-base imbalances, or hepatic or renal failure. Called also acute confusional state and acute brain syndrome. [EU] Delivery of Health Care: The concept concerned with all aspects of providing and distributing health services to a patient population. [NIH] Delusion: A false belief, not susceptible to argument or reason, and determined,
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pathologically, by some form of mental disorder. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Depersonalization: Alteration in the perception of the self so that the usual sense of one's own reality is lost, manifested in a sense of unreality or self-estrangement, in changes of body image, or in a feeling that one does not control his own actions and speech; seen in depersonalization disorder, schizophrenic disorders, and schizotypal personality disorder. Some do not draw a distinction between depersonalization and derealization, using depersonalization to include both. [EU] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] 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] Derealization: Is characterized by the loss of the sense of reality concerning one's surroundings. [NIH] Dermal: Pertaining to or coming from the skin. [NIH] Dermatitis: Any inflammation of the skin. [NIH] Dermatitis Herpetiformis: Rare, chronic, papulo-vesicular disease characterized by an intensely pruritic eruption consisting of various combinations of symmetrical, erythematous, papular, vesicular, or bullous lesions. The disease is strongly associated with the presence of HLA-B8 and HLA-DR3 antigens. A variety of different autoantibodies has been detected in small numbers in patients with dermatitis herpetiformis. [NIH] Dermatosis: Any skin disease, especially one not characterized by inflammation. [EU] Desensitization: The prevention or reduction of immediate hypersensitivity reactions by administration of graded doses of allergen; called also hyposensitization and immunotherapy. [EU] Detoxification: Treatment designed to free an addict from his drug habit. [EU] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Dialyzer: A part of the hemodialysis machine. (See hemodialysis under dialysis.) The dialyzer has two sections separated by a membrane. One section holds dialysate. The other holds the patient's blood. [NIH] Diaphoresis: Perspiration, especially profuse perspiration. Called also sudoresis. [EU]
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Diaphragm: The musculofibrous partition that separates the thoracic cavity from the abdominal cavity. Contraction of the diaphragm increases the volume of the thoracic cavity aiding inspiration. [NIH] 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] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Digitalis: A genus of toxic herbaceous Eurasian plants of the Scrophulaceae which yield cardiotonic glycosides. The most useful are Digitalis lanata and D. purpurea. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Dilatation: The act of dilating. [NIH] Dilation: A process by which the pupil is temporarily enlarged with special eye drops (mydriatic); allows the eye care specialist to better view the inside of the eye. [NIH] Dimethyl: A volatile metabolite of the amino acid methionine. [NIH] Diphenhydramine: A histamine H1 antagonist used as an antiemetic, antitussive, for dermatoses and pruritus, for hypersensitivity reactions, as a hypnotic, an antiparkinson, and as an ingredient in common cold preparations. It has some undesired antimuscarinic and sedative effects. [NIH] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis. [NIH] Disease Transmission: The transmission of infectious disease or pathogens. When transmission is within the same species, the mode can be horizontal (disease transmission, horizontal) or vertical (disease transmission, vertical). [NIH] Disease Transmission, Horizontal: The transmission of infectious disease or pathogens from one individual to another in the same generation. [NIH] Disease Transmission, Vertical: The transmission of infectious disease or pathogens from one generation to another. It includes transmission in utero or intrapartum by exposure to blood and secretions, and postpartum exposure via breastfeeding. [NIH] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Disorientation: The loss of proper bearings, or a state of mental confusion as to time, place, or identity. [EU] 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
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molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Diuresis: Increased excretion of urine. [EU] Diurnal: Occurring during the day. [EU] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Doxepin: A dibenzoxepin tricyclic compound. It displays a range of pharmacological actions including maintaining adrenergic innervation. Its mechanism of action is not fully understood, but it appears to block reuptake of monoaminergic neurotransmitters into presynaptic terminals. It also possesses anticholinergic activity and modulates antagonism of histamine H(1)- and H(2)-receptors. [NIH] 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] Drinking Behavior: Behaviors associated with the ingesting of water and other liquids; includes rhythmic patterns of drinking (time intervals - onset and duration), frequency and satiety. [NIH] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Resistance: Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from drug tolerance which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Duct: A tube through which body fluids pass. [NIH] Duodenum: The first part of the small intestine. [NIH]
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Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dyskinesia: Impairment of the power of voluntary movement, resulting in fragmentary or incomplete movements. [EU] Dyspareunia: Painful sexual intercourse. [NIH] Dyspepsia: Impaired digestion, especially after eating. [NIH] Dysphoric: A feeling of unpleasantness and discomfort. [NIH] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dyspnea: Difficult or labored breathing. [NIH] Dystonia: Disordered tonicity of muscle. [EU] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Eating Disorders: A group of disorders characterized by physiological and psychological disturbances in appetite or food intake. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Effector cell: A cell that performs a specific function in response to a stimulus; usually used to describe cells in the immune system. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] 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] Electrode: Component of the pacing system which is at the distal end of the lead. It is the interface with living cardiac tissue across which the stimulus is transmitted. [NIH] 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] Electrolysis: Destruction by passage of a galvanic electric current, as in disintegration of a chemical compound in solution. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH]
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]
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Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Emphysema: A pathological accumulation of air in tissues or organs. [NIH] 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] Encephalopathy: A disorder of the brain that can be caused by disease, injury, drugs, or chemicals. [NIH] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endocarditis: Exudative and proliferative inflammatory alterations of the endocardium, characterized by the presence of vegetations on the surface of the endocardium or in the endocardium itself, and most commonly involving a heart valve, but sometimes affecting the inner lining of the cardiac chambers or the endocardium elsewhere. It may occur as a primary disorder or as a complication of or in association with another disease. [EU] Endocrine System: The system of glands that release their secretions (hormones) directly into the circulatory system. In addition to the endocrine glands, included are the chromaffin system and the neurosecretory systems. [NIH] Endometrial: Having to do with the endometrium (the layer of tissue that lines the uterus). [NIH]
Endometrium: The layer of tissue that lines the uterus. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxin: Toxin from cell walls of bacteria. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Energy balance: Energy is the capacity of a body or a physical system for doing work. Energy balance is the state in which the total energy intake equals total energy needs. [NIH] Enhancer: Transcriptional element in the virus genome. [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.
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[NIH]
Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Eosinophils: Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidemiological: Relating to, or involving epidemiology. [EU] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epidermoid carcinoma: A type of cancer in which the cells are flat and look like fish scales. Also called squamous cell carcinoma. [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Erectile: The inability to get or maintain an erection for satisfactory sexual intercourse. Also called impotence. [NIH] Erection: The condition of being made rigid and elevated; as erectile tissue when filled with blood. [EU] Erythema: Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of causes. [NIH] Erythrina: A genus of leguminous shrubs or trees, mainly tropical, yielding certain alkaloids, lectins, and other useful compounds. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Escalation: Progressive use of more harmful drugs. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]
Essential Tremor: A rhythmic, involuntary, purposeless, oscillating movement resulting from the alternate contraction and relaxation of opposing groups of muscles. [NIH] Estrogen: One of the two female sex hormones. [NIH] Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Eukaryote: An organism (or a cell) that carries its genetic material physically constrained within a nuclear membrane, separate from the cytoplasm. [NIH] Evacuation: An emptying, as of the bowels. [EU]
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Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Excitability: Property of a cardiac cell whereby, when the cell is depolarized to a critical level (called threshold), the membrane becomes permeable and a regenerative inward current causes an action potential. [NIH] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] Exhaustion: The feeling of weariness of mind and body. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exon: The part of the DNA that encodes the information for the actual amino acid sequence of the protein. In many eucaryotic genes, the coding sequences consist of a series of exons alternating with intron sequences. [NIH] Expiration: The act of breathing out, or expelling air from the lungs. [EU] Extensor: A muscle whose contraction tends to straighten a limb; the antagonist of a flexor. [NIH]
External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extrapyramidal: Outside of the pyramidal tracts. [EU] Exudate: Material, such as fluid, cells, or cellular debris, which has escaped from blood vessels and has been deposited in tissues or on tissue surfaces, usually as a result of inflammation. An exudate, in contrast to a transudate, is characterized by a high content of protein, cells, or solid materials derived from cells. [EU] Facial: Of or pertaining to the face. [EU] Facial Pain: Pain in the facial region including orofacial pain and craniofacial pain. Associated conditions include local inflammatory and neoplastic disorders and neuralgic syndromes involving the trigeminal, facial, and glossopharyngeal nerves. Conditions which feature recurrent or persistent facial pain as the primary manifestation of disease are referred to as facial pain syndromes. [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] 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] Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH]
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Flatus: Gas passed through the rectum. [NIH] Flexor: Muscles which flex a joint. [NIH] Fluoxetine: The first highly specific serotonin uptake inhibitor. It is used as an antidepressant and often has a more acceptable side-effects profile than traditional antidepressants. [NIH] Foramen: A natural hole of perforation, especially one in a bone. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Frameshift: A type of mutation which causes out-of-phase transcription of the base sequence; such mutations arise from the addition or delection of nucleotide(s) in numbers other than 3 or multiples of 3. [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] Fungus: A general term used to denote a group of eukaryotic protists, including mushrooms, yeasts, rusts, moulds, smuts, etc., which are characterized by the absence of chlorophyll and by the presence of a rigid cell wall composed of chitin, mannans, and sometimes cellulose. They are usually of simple morphological form or show some reversible cellular specialization, such as the formation of pseudoparenchymatous tissue in the fruiting body of a mushroom. The dimorphic fungi grow, according to environmental conditions, as moulds or yeasts. [EU] 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] Ganglion: 1. A knot, or knotlike mass. 2. A general term for a group of nerve cell bodies located outside the central nervous system; occasionally applied to certain nuclear groups within the brain or spinal cord, e.g. basal ganglia. 3. A benign cystic tumour occurring on a aponeurosis or tendon, as in the wrist or dorsum of the foot; it consists of a thin fibrous capsule enclosing a clear mucinous fluid. [EU] 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] Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories. [NIH] 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.
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[NIH]
Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] 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] Genomics: The systematic study of the complete DNA sequences (genome) of organisms. [NIH]
Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Geriatric: Pertaining to the treatment of the aged. [EU] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Gestures: Movement of a part of the body for the purpose of communication. [NIH] Ginseng: An araliaceous genus of plants that contains a number of pharmacologically active agents used as stimulants, sedatives, and tonics, especially in traditional medicine. [NIH] 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] Glossopharyngeal Nerve: The 9th cranial nerve. The glossopharyngeal nerve is a mixed motor and sensory nerve; it conveys somatic and autonomic efferents as well as general, special, and visceral afferents. Among the connections are motor fibers to the stylopharyngeus muscle, parasympathetic fibers to the parotid glands, general and taste afferents from the posterior third of the tongue, the nasopharynx, and the palate, and afferents from baroreceptors and chemoreceptors of the carotid sinus. [NIH] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [NIH] 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.
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[NIH]
Gluten: The protein of wheat and other grains which gives to the dough its tough elastic character. [EU] 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] Glycopeptides: Proteins which contain carbohydrate groups attached covalently to the polypeptide chain. The protein moiety is the predominant group with the carbohydrate making up only a small percentage of the total weight. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycosylation: The chemical or biochemical addition of carbohydrate or glycosyl groups to other chemicals, especially peptides or proteins. Glycosyl transferases are used in this biochemical reaction. [NIH] Goats: Any of numerous agile, hollow-horned ruminants of the genus Capra, closely related to the sheep. [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] 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] Granule: A small pill made from sucrose. [EU] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] 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] 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] Hair Cells: Mechanoreceptors located in the organ of Corti that are sensitive to auditory stimuli and in the vestibular apparatus that are sensitive to movement of the head. In each case the accessory sensory structures are arranged so that appropriate stimuli cause movement of the hair-like projections (stereocilia and kinocilia) which relay the information centrally in the nervous system. [NIH] Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. [NIH] Hallucinogens: Drugs capable of inducing illusions, hallucinations, delusions, paranoid ideations, and other alterations of mood and thinking. Despite the name, the feature that distinguishes these agents from other classes of drugs is their capacity to induce states of altered perception, thought, and feeling that are not experienced otherwise. [NIH] Haploid: An organism with one basic chromosome set, symbolized by n; the normal
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condition of gametes in diploids. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Headache Disorders: Common conditions characterized by persistent or recurrent headaches. Headache syndrome classification systems may be based on etiology (e.g., vascular headache, post-traumatic headaches, etc.), temporal pattern (e.g., cluster headache, paroxysmal hemicrania, etc.), and precipitating factors (e.g., cough headache). [NIH] Health Care Costs: The actual costs of providing services related to the delivery of health care, including the costs of procedures, therapies, and medications. It is differentiated from health expenditures, which refers to the amount of money paid for the services, and from fees, which refers to the amount charged, regardless of cost. [NIH] Health Education: Education that increases the awareness and favorably influences the attitudes and knowledge relating to the improvement of health on a personal or community basis. [NIH] Health Expenditures: The amounts spent by individuals, groups, nations, or private or public organizations for total health care and/or its various components. These amounts may or may not be equivalent to the actual costs (health care costs) and may or may not be shared among the patient, insurers, and/or employers. [NIH] Hearing aid: A miniature, portable sound amplifier for persons with impaired hearing, consisting of a microphone, audio amplifier, earphone, and battery. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heartburn: Substernal pain or burning sensation, usually associated with regurgitation of gastric juice into the esophagus. [NIH] Hematocrit: Measurement of the volume of packed red cells in a blood specimen by centrifugation. The procedure is performed using a tube with graduated markings or with automated blood cell counters. It is used as an indicator of erythrocyte status in disease. For example, anemia shows a low hematocrit, polycythemia, high values. [NIH] Hemicrania: An ache or a pain in one side of the head, as in migraine. [NIH] Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemoglobinuria: The presence of free hemoglobin in the urine. [NIH]
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Hemolysis: The destruction of erythrocytes by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity. [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] Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used alone, the term may refer to herpes simplex or to herpes zoster. [EU] Herpes Zoster: Acute vesicular inflammation. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]
Heterozygotes: Having unlike alleles at one or more corresponding loci on homologous chromosomes. [NIH] Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Holidays: Days commemorating events. Holidays also include vacation periods. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Hormone Replacement Therapy: Therapeutic use of hormones to alleviate the effects of hormone deficiency. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] 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
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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] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydroxylamines: Organic compounds that contain the (-NH2OH) radical. [NIH] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hyperphagia: Ingestion of a greater than optimal quantity of food. [NIH] Hyperplasia: An increase in the number of cells in a tissue or organ, not due to tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hypesthesia: Absent or reduced sensitivity to cutaneous stimulation. [NIH] Hypnotherapy: Sleeping-cure. [NIH] Hypnotic: A drug that acts to induce sleep. [EU] Hypoglycaemia: An abnormally diminished concentration of glucose in the blood, which may lead to tremulousness, cold sweat, piloerection, hypothermia, and headache, accompanied by irritability, confusion, hallucinations, bizarre behaviour, and ultimately, convulsions and coma. [EU] Hypoglycemia: Abnormally low blood sugar [NIH] Hypokinesia: Slow or diminished movement of body musculature. It may be associated with basal ganglia diseases; mental disorders; prolonged inactivity due to illness; experimental protocols used to evaluate the physiologic effects of immobility; and other conditions. [NIH] Hypotension: Abnormally low blood pressure. [NIH] Hypothalamic: Of or involving the hypothalamus. [EU] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Hysteria: Historical term for a chronic, but fluctuating, disorder beginning in early life and characterized by recurrent and multiple somatic complaints not apparently due to physical illness. This diagnosis is not used in contemporary practice. [NIH]
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Iatrogenic: Resulting from the activity of physicians. Originally applied to disorders induced in the patient by autosuggestion based on the physician's examination, manner, or discussion, the term is now applied to any adverse condition in a patient occurring as the result of treatment by a physician or surgeon, especially to infections acquired by the patient during the course of treatment. [EU] Iatrogenic Disease: Any adverse condition in a patient occurring as the result of treatment by a physician, surgeon, or other health professional, especially infections acquired by the patient during the course of treatment. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Imbedding: The implantation of the fertilized ovum in the endometrium of the pregnant uterus. [NIH] Imipramine: The prototypical tricyclic antidepressant. It has been used in major depression, dysthymia, bipolar depression, attention-deficit disorders, agoraphobia, and panic disorders. It has less sedative effect than some other members of this therapeutic group. [NIH]
Immune function: Production and action of cells that fight disease or infection. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]
Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]
effects
of
foreign
Immunoassay: Immunochemical assay or detection of a substance by serologic or immunologic methods. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance. [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunodeficiency syndrome: The inability of the body to produce an immune response. [NIH]
Immunoglobulins: Glycoproteins present in the blood (antibodies) and in other tissue. They are classified by structure and activity into five classes (IgA, IgD, IgE, IgG, IgM). [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] Impotence: The inability to perform sexual intercourse. [NIH]
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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] 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] Indigestion: Poor digestion. Symptoms include heartburn, nausea, bloating, and gas. Also called dyspepsia. [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]
Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Initiator: A chemically reactive substance which may cause cell changes if ingested, inhaled or absorbed into the body; the substance may thus initiate a carcinogenic process. [NIH] Inlay: In dentistry, a filling first made to correspond with the form of a dental cavity and then cemented into the cavity. [NIH] Innervation: 1. The distribution or supply of nerves to a part. 2. The supply of nervous energy or of nerve stimulus sent to a part. [EU] Inorganic: Pertaining to substances not of organic origin. [EU] Inositol: An isomer of glucose that has traditionally been considered to be a B vitamin although it has an uncertain status as a vitamin and a deficiency syndrome has not been identified in man. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1379) Inositol phospholipids are important in signal transduction. [NIH] Inotropic: Affecting the force or energy of muscular contractions. [EU] Insight: The capacity to understand one's own motives, to be aware of one's own
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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] 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 radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [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] Intramuscular: IM. Within or into muscle. [NIH] Intraocular: Within the eye. [EU] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]
Involuntary: Reaction occurring without intention or volition. [NIH] 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] 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]
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Iris: The most anterior portion of the uveal layer, separating the anterior chamber from the posterior. It consists of two layers - the stroma and the pigmented epithelium. Color of the iris depends on the amount of melanin in the stroma on reflection from the pigmented epithelium. [NIH] Irradiation: The use of high-energy radiation from x-rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Irradiation is also called radiation therapy, radiotherapy, and x-ray therapy. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Jealousy: An irrational reaction compounded of grief, loss of self-esteem, enmity against the rival and self criticism. [NIH] 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] Kava: Dried rhizome and roots of Piper methysticum, a shrub native to Oceania and known for its anti-anxiety and sedative properties. Heavy usage results in some adverse effects. It contains alkaloids, lactones, kawain, methysticin, mucilage, starch, and yangonin. Kava is also the name of the pungent beverage prepared from the plant's roots. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Kidney Failure: The inability of a kidney to excrete metabolites at normal plasma levels under conditions of normal loading, or the inability to retain electrolytes under conditions of normal intake. In the acute form (kidney failure, acute), it is marked by uremia and usually by oliguria or anuria, with hyperkalemia and pulmonary edema. The chronic form (kidney failure, chronic) is irreversible and requires hemodialysis. [NIH] Kidney stone: A stone that develops from crystals that form in urine and build up on the inner surfaces of the kidney, in the renal pelvis, or in the ureters. [NIH] 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] Larynx: An irregularly shaped, musculocartilaginous tubular structure, lined with mucous membrane, located at the top of the trachea and below the root of the tongue and the hyoid bone. It is the essential sphincter guarding the entrance into the trachea and functioning secondarily as the organ of voice. [NIH] Latency: The period of apparent inactivity between the time when a stimulus is presented and the moment a response occurs. [NIH]
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Least-Squares Analysis: A principle of estimation in which the estimates of a set of parameters in a statistical model are those quantities minimizing the sum of squared differences between the observed values of a dependent variable and the values predicted by the model. [NIH] Lectins: Protein or glycoprotein substances, usually of plant origin, that bind to sugar moieties in cell walls or membranes and thereby change the physiology of the membrane to cause agglutination, mitosis, or other biochemical changes in the cell. [NIH] Leishmaniasis: A disease caused by any of a number of species of protozoa in the genus Leishmania. There are four major clinical types of this infection: cutaneous (Old and New World), diffuse cutaneous, mucocutaneous, and visceral leishmaniasis. [NIH] Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] Leprosy: A chronic granulomatous infection caused by Mycobacterium leprae. The granulomatous lesions are manifested in the skin, the mucous membranes, and the peripheral nerves. Two polar or principal types are lepromatous and tuberculoid. [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] Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Leukotrienes: A family of biologically active compounds derived from arachidonic acid by oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal tract and the immune system. [NIH] Libido: The psychic drive or energy associated with sexual instinct in the broad sense (pleasure and love-object seeking). It may also connote the psychic energy associated with instincts in general that motivate behavior. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]
Lichen Planus: An inflammatory, pruritic disease of the skin and mucous membranes, which can be either generalized or localized. It is characterized by distinctive purplish, flattopped papules having a predilection for the trunk and flexor surfaces. The lesions may be discrete or coalesce to form plaques. Histologically, there is a "saw-tooth" pattern of epidermal hyperplasia and vacuolar alteration of the basal layer of the epidermis along with an intense upper dermal inflammatory infiltrate composed predominantly of T-cells. Etiology is unknown. [NIH] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Ligands: A RNA simulation method developed by the MIT. [NIH] Likelihood Functions: Functions constructed from a statistical model and a set of observed data which give the probability of that data for various values of the unknown model parameters. Those parameter values that maximize the probability are the maximum likelihood estimates of the parameters. [NIH]
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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] Linear Models: Statistical models in which the value of a parameter for a given value of a factor is assumed to be equal to a + bx, where a and b are constants. The models predict a linear regression. [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] Lipolysis: The hydrolysis of lipids. [NIH] Lipoxygenase: An enzyme of the oxidoreductase class that catalyzes reactions between linoleate and other fatty acids and oxygen to form hydroperoxy-fatty acid derivatives. Related enzymes in this class include the arachidonate lipoxygenases, arachidonate 5lipoxygenase, arachidonate 12-lipoxygenase, and arachidonate 15-lipoxygenase. EC 1.13.11.12. [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] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH] Locomotor: Of or pertaining to locomotion; pertaining to or affecting the locomotive apparatus of the body. [EU] Logistic Models: Statistical models which describe the relationship between a qualitative dependent variable (that is, one which can take only certain discrete values, such as the presence or absence of a disease) and an independent variable. A common application is in epidemiology for estimating an individual's risk (probability of a disease) as a function of a given risk factor. [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]
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Long-Term Care: Care over an extended period, usually for a chronic condition or disability, requiring periodic, intermittent, or continuous care. [NIH] Loop: A wire usually of platinum bent at one end into a small loop (usually 4 mm inside diameter) and used in transferring microorganisms. [NIH] Lorazepam: An anti-anxiety agent with few side effects. It also has hypnotic, anticonvulsant, and considerable sedative properties and has been proposed as a preanesthetic agent. [NIH] 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]
Luciferase: Any one of several enzymes that catalyze the bioluminescent reaction in certain marine crustaceans, fish, bacteria, and insects. The enzyme is a flavoprotein; it oxidizes luciferins to an electronically excited compound that emits energy in the form of light. The color of light emitted varies with the organism. The firefly enzyme is a valuable reagent for measurement of ATP concentration. (Dorland, 27th ed) EC 1.13.12.-. [NIH] Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Macula: A stain, spot, or thickening. Often used alone to refer to the macula retinae. [EU] Macula Lutea: An oval area in the retina, 3 to 5 mm in diameter, usually located temporal to the superior pole of the eye and slightly below the level of the optic disk. [NIH] Macular Degeneration: Degenerative changes in the macula lutea of the retina. [NIH] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malaria: A protozoan disease caused in humans by four species of the genus Plasmodium (P. falciparum (malaria, falciparum), P. vivax (malaria, vivax), P. ovale, and P. malariae) and transmitted by the bite of an infected female mosquito of the genus Anopheles. Malaria is endemic in parts of Asia, Africa, Central and South America, Oceania, and certain Caribbean islands. It is characterized by extreme exhaustion associated with paroxysms of high fever, sweating, shaking chills, and anemia. Malaria in animals is caused by other species of plasmodia. [NIH] Malaria, Falciparum: Malaria caused by Plasmodium falciparum. This is the severest form of malaria and is associated with the highest levels of parasites in the blood. This disease is characterized by irregularly recurring febrile paroxysms that in extreme cases occur with acute cerebral, renal, or gastrointestinal manifestations. [NIH] Malaria, Vivax: Malaria caused by Plasmodium vivax. This form of malaria is less severe than malaria, falciparum, but there is a higher probability for relapses to occur. Febrile paroxysms often occur every other day. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malingering: Simulation of symptoms of illness or injury with intent to deceive in order to obtain a goal, e.g., a claim of physical illness to avoid jury duty. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]
Mammogram: An x-ray of the breast. [NIH]
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Mandible: The largest and strongest bone of the face constituting the lower jaw. It supports the lower teeth. [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] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Mastication: The act and process of chewing and grinding food in the mouth. [NIH] Maximum Tolerated Dose: The highest dose level eliciting signs of toxicity without having major effects on survival relative to the test in which it is used. [NIH] Meatus: A canal running from the internal auditory foramen through the petrous portion of the temporal bone. It gives passage to the facial and auditory nerves together with the auditory branch of the basilar artery and the internal auditory veins. [NIH] Mechanical ventilation: Use of a machine called a ventilator or respirator to improve the exchange of air between the lungs and the atmosphere. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medical Records: Recording of pertinent information concerning patient's illness or illnesses. [NIH] 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] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells. [NIH] Membrane Potentials: Ratio of inside versus outside concentration of potassium, sodium, chloride and other ions in diffusible tissues or cells. Also called transmembrane and resting potentials, they are measured by recording electrophysiologic responses in voltagedependent ionic channels of (e.g.) nerve, muscle and blood cells as well as artificial membranes. [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]
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Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Meningitis: Inflammation of the meninges. When it affects the dura mater, the disease is termed pachymeningitis; when the arachnoid and pia mater are involved, it is called leptomeningitis, or meningitis proper. [EU] Menopause: Permanent cessation of menstruation. [NIH] Menstrual Cycle: The period of the regularly recurring physiologic changes in the endometrium occurring during the reproductive period in human females and some primates and culminating in partial sloughing of the endometrium (menstruation). [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mental Processes: Conceptual functions or thinking in all its forms. [NIH] Mental Retardation: Refers to sub-average general intellectual functioning which originated during the developmental period and is associated with impairment in adaptive behavior. [NIH]
Mentors: Senior professionals who provide guidance, direction and support to those persons desirous of improvement in academic positions, administrative positions or other career development situations. [NIH] 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] Mesolimbic: Inner brain region governing emotion and drives. [NIH] Meta-Analysis: A quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with application chiefly in the areas of research and medicine. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metabotropic: A glutamate receptor which triggers an increase in production of 2 intracellular messengers: diacylglycerol and inositol 1, 4, 5-triphosphate. [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] Mianserin: A tetracyclic compound with antidepressant effects. It may cause drowsiness and hematological problems. Its mechanism of therapeutic action is not well understood, although it apparently blocks alpha-adrenergic, histamine H1, and some types of serotonin receptors. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH]
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Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microcalcifications: Tiny deposits of calcium in the breast that cannot be felt but can be detected on a mammogram. A cluster of these very small specks of calcium may indicate that cancer is present. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Middle Cerebral Artery: The largest and most complex of the cerebral arteries. Branches of the middle cerebral artery supply the insular region, motor and premotor areas, and large regions of the association cortex. [NIH] Milliliter: A measure of volume for a liquid. A milliliter is approximately 950-times smaller than a quart and 30-times smaller than a fluid ounce. A milliliter of liquid and a cubic centimeter (cc) of liquid are the same. [NIH] Miscible: Susceptible of being mixed. [EU] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Modulator: A specific inductor that brings out characteristics peculiar to a definite region. [EU]
Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoamine: Enzyme that breaks down dopamine in the astrocytes and microglia. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] 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] Mood Disorders: Those disorders that have a disturbance in mood as their predominant feature. [NIH] Morphine: The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. [NIH] Morphological: Relating to the configuration or the structure of live organs. [NIH] Motility: The ability to move spontaneously. [EU]
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Motion Pictures: The art, technique, or business of producing motion pictures for entertainment, propaganda, or instruction. [NIH] 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] Muscle Fibers: Large single cells, either cylindrical or prismatic in shape, that form the basic unit of muscle tissue. They consist of a soft contractile substance enclosed in a tubular sheath. [NIH] Muscle relaxant: An agent that specifically aids in reducing muscle tension, as those acting at the polysynaptic neurons of motor nerves (e.g. meprobamate) or at the myoneural junction (curare and related compounds). [EU] Muscle Relaxation: That phase of a muscle twitch during which a muscle returns to a resting position. [NIH] Muscle tension: A force in a material tending to produce extension; the state of being stretched. [NIH] Muscular Atrophy: Derangement in size and number of muscle fibers occurring with aging, reduction in blood supply, or following immobilization, prolonged weightlessness, malnutrition, and particularly in denervation. [NIH] Muscular Dystrophies: A general term for a group of inherited disorders which are characterized by progressive degeneration of skeletal muscles. [NIH] Musculature: The muscular apparatus of the body, or of any part of it. [EU] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myopathy: Any disease of a muscle. [EU] Myotonic Dystrophy: A condition presenting muscle weakness and wasting which may be progressive. [NIH] Naive: Used to describe an individual who has never taken a certain drug or class of drugs (e. g., AZT-naive, antiretroviral-naive), or to refer to an undifferentiated immune system cell. [NIH] Naloxone: A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors. [NIH] Naltrexone: Derivative of noroxymorphone that is the N-cyclopropylmethyl congener of naloxone. It is a narcotic antagonist that is effective orally, longer lasting and more potent than naloxone, and has been proposed for the treatment of heroin addiction. The FDA has
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approved naltrexone for the treatment of alcohol dependence. [NIH] Narcolepsy: A condition of unknown cause characterized by a periodic uncontrollable tendency to fall asleep. [NIH] Narcosis: A general and nonspecific reversible depression of neuronal excitability, produced by a number of physical and chemical aspects, usually resulting in stupor. [NIH] Narcotic: 1. Pertaining to or producing narcosis. 2. An agent that produces insensibility or stupor, applied especially to the opioids, i.e. to any natural or synthetic drug that has morphine-like actions. [EU] Nasopharynx: The nasal part of the pharynx, lying above the level of the soft palate. [NIH] Natural selection: A part of the evolutionary process resulting in the survival and reproduction of the best adapted individuals. [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] 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] Neonatal: Pertaining to the first four weeks after birth. [EU] Neonatal Abstinence Syndrome: Fetal and neonatal addiction and withdrawal as a result of the mother's dependence on drugs during pregnancy. Withdrawal or abstinence symptoms develop shortly after birth. Symptoms exhibited are loud, high-pitched crying, sweating, yawning and gastrointestinal disturbances. [NIH] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Nephropathy: Disease of the kidneys. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nerve Fibers: Slender processes of neurons, especially the prolonged axons that conduct nerve impulses. [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] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU]
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Neuralgia: Intense or aching pain that occurs along the course or distribution of a peripheral or cranial nerve. [NIH] Neurasthenia: A mental disorder characterized by chronic fatigue and concomitant physiologic symptoms. [NIH] Neuritis: A general term indicating inflammation of a peripheral or cranial nerve. Clinical manifestation may include pain; paresthesias; paresis; or hypesthesia. [NIH] Neurodegenerative Diseases: Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures. [NIH] 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] Neuroleptic: A term coined to refer to the effects on cognition and behaviour of antipsychotic drugs, which produce a state of apathy, lack of initiative, and limited range of emotion and in psychotic patients cause a reduction in confusion and agitation and normalization of psychomotor activity. [EU] Neurologic: Having to do with nerves or the nervous system. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropathy: A problem in any part of the nervous system except the brain and spinal cord. Neuropathies can be caused by infection, toxic substances, or disease. [NIH] 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] Neurosis: Functional derangement due to disorders of the nervous system which does not affect the psychic personality of the patient. [NIH] Neurotic: 1. Pertaining to or characterized by neurosis. 2. A person affected with a neurosis. [EU]
Neurotic Disorders: Disorders in which the symptoms are distressing to the individual and recognized by him or her as being unacceptable. Social relationships may be greatly affected but usually remain within acceptable limits. The disturbance is relatively enduring or recurrent without treatment. [NIH] Neurotransmitters: Endogenous signaling molecules that alter the behavior of neurons or effector cells. Neurotransmitter is used here in its most general sense, including not only messengers that act directly to regulate ion channels, but also those that act through second messenger systems, and those that act at a distance from their site of release. Included are neuromodulators, neuroregulators, neuromediators, and neurohumors, whether or not acting at synapses. [NIH] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are
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unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutrophils: Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. [NIH] Niacin: Water-soluble vitamin of the B complex occurring in various animal and plant tissues. Required by the body for the formation of coenzymes NAD and NADP. Has pellagra-curative, vasodilating, and antilipemic properties. [NIH] Night Blindness: Anomaly of vision in which there is a pronounced inadequacy or complete absence of dark-adaptation. [NIH] Nimodipine: A calcium channel blockader with preferential cerebrovascular activity. It has marked cerebrovascular dilating effects and lowers blood pressure. [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] Nonmetastatic: Cancer that has not spread from the primary (original) site to other sites in the body. [NIH] Nonverbal Communication: Transmission of emotions, ideas, and attitudes between individuals in ways other than the spoken language. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleolus: A small dense body (sub organelle) within the nucleus of eukaryotic cells, visible by phase contrast and interference microscopy in live cells throughout interphase. Contains RNA and protein and is the site of synthesis of ribosomal RNA. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH]
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Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Odour: A volatile emanation that is perceived by the sense of smell. [EU] Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or allow the uncontrolled growth of cancer. Alterations can be inherited or caused by an environmental exposure to carcinogens. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Opium: The air-dried exudate from the unripe seed capsule of the opium poppy, Papaver somniferum, or its variant, P. album. It contains a number of alkaloids, but only a few morphine, codeine, and papaverine - have clinical significance. Opium has been used as an analgesic, antitussive, antidiarrheal, and antispasmodic. [NIH] Opportunistic Infections: An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression. [NIH] Optic Chiasm: The X-shaped structure formed by the meeting of the two optic nerves. At the optic chiasm the fibers from the medial part of each retina cross to project to the other side of the brain while the lateral retinal fibers continue on the same side. As a result each half of the brain receives information about the contralateral visual field from both eyes. [NIH]
Optic Nerve: The 2nd cranial nerve. The optic nerve conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other important targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. [NIH] Orofacial: Of or relating to the mouth and face. [EU] Orthostatic: Pertaining to or caused by standing erect. [EU] Osmosis: Tendency of fluids (e.g., water) to move from the less concentrated to the more concentrated side of a semipermeable membrane. [NIH] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] Osteoarthritis: A progressive, degenerative joint disease, the most common form of arthritis, especially in older persons. The disease is thought to result not from the aging process but from biochemical changes and biomechanical stresses affecting articular cartilage. In the foreign literature it is often called osteoarthrosis deformans. [NIH] Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [NIH] 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] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxazepam: A benzodiazepine used in the treatment of anxiety, alcohol withdrawal, and insomnia. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation)
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from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]
Oxidative metabolism: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as aerobic respiration, cell respiration, or aerobic metabolism. [NIH] Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] 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] 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 cancer: Cancer of the pancreas, a salivary gland of the abdomen. [NIH] Pancreatic Juice: The fluid containing digestive enzymes secreted by the pancreas in response to food in the duodenum. [NIH] Pancreatitis: Acute or chronic inflammation of the pancreas, which may be asymptomatic or symptomatic, and which is due to autodigestion of a pancreatic tissue by its own enzymes. It is caused most often by alcoholism or biliary tract disease; less commonly it may be associated with hyperlipaemia, hyperparathyroidism, abdominal trauma (accidental or operative injury), vasculitis, or uraemia. [EU] Panic: A state of extreme acute, intense anxiety and unreasoning fear accompanied by disorganization of personality function. [NIH] Panic Disorder: A type of anxiety disorder characterized by unexpected panic attacks that last minutes or, rarely, hours. Panic attacks begin with intense apprehension, fear or terror and, often, a feeling of impending doom. Symptoms experienced during a panic attack include dyspnea or sensations of being smothered; dizziness, loss of balance or faintness; choking sensations; palpitations or accelerated heart rate; shakiness; sweating; nausea or other form of abdominal distress; depersonalization or derealization; paresthesias; hot flashes or chills; chest discomfort or pain; fear of dying and fear of not being in control of oneself or going crazy. Agoraphobia may also develop. Similar to other anxiety disorders, it may be inherited as an autosomal dominant trait. [NIH] Papaverine: An alkaloid found in opium but not closely related to the other opium alkaloids in its structure or pharmacological actions. It is a direct-acting smooth muscle relaxant used in the treatment of impotence and as a vasodilator, especially for cerebral vasodilation. The mechanism of its pharmacological actions is not clear, but it apparently can inhibit phosphodiesterases and it may have direct actions on calcium channels. [NIH] Paralysis: Loss of ability to move all or part of the body. [NIH] Paranoia: A psychotic disorder marked by persistent delusions of persecution or delusional jealousy and behaviour like that of the paranoid personality, such as suspiciousness,
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mistrust, and combativeness. It differs from paranoid schizophrenia, in which hallucinations or formal thought disorder are present, in that the delusions are logically consistent and that there are no other psychotic features. The designation in DSM III-R is delusional (paranoid) disorders, with five types : persecutory, jealous, erotomanic, somatic, and grandiose. [EU] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Paresis: A general term referring to a mild to moderate degree of muscular weakness, occasionally used as a synonym for paralysis (severe or complete loss of motor function). In the older literature, paresis often referred specifically to paretic neurosyphilis. "General paresis" and "general paralysis" may still carry that connotation. Bilateral lower extremity paresis is referred to as paraparesis. [NIH] Paresthesias: Abnormal touch sensations, such as burning or prickling, that occur without an outside stimulus. [NIH] Parkinsonism: A group of neurological disorders characterized by hypokinesia, tremor, and muscular rigidity. [EU] Parotid: The space that contains the parotid gland, the facial nerve, the external carotid artery, and the retromandibular vein. [NIH] 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] Particle: A tiny mass of material. [EU] Partnership Practice: A voluntary contract between two or more doctors who may or may not share responsibility for the care of patients, with proportional sharing of profits and losses. [NIH] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Pathogen: Any disease-producing microorganism. [EU] 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]
Patient Satisfaction: The degree to which the individual regards the health care service or product or the manner in which it is delivered by the provider as useful, effective, or beneficial. [NIH] PDQ: Physician Data Query. PDQ is an online database developed and maintained by the National Cancer Institute. Designed to make the most current, credible, and accurate cancer
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information available to health professionals and the public, PDQ contains peer-reviewed summaries on cancer treatment, screening, prevention, genetics, and supportive care; a registry of cancer clinical trials from around the world; and directories of physicians, professionals who provide genetics services, and organizations that provide cancer care. Most of this information is available on the CancerNet Web site, and more specific information about PDQ can be found at http://cancernet.nci.nih.gov/pdq.html. [NIH] Pelvic: Pertaining to the pelvis. [EU] Penicillin: An antibiotic drug used to treat infection. [NIH] Pentamidine: Antiprotozoal agent effective in trypanosomiasis, leishmaniasis, and some fungal infections; used in treatment of Pneumocystis carinii pneumonia in HIV-infected patients. It may cause diabetes mellitus, central nervous system damage, and other toxic effects. [NIH] Pentylenetetrazole: A pharmaceutical agent that displays activity as a central nervous system and respiratory stimulant. It is considered a non-competitive GABA antagonist. Pentylenetetrazole has been used experimentally to study seizure phenomenon and to identify pharmaceuticals that may control seizure susceptibility. [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] Perimenopausal: The time of a woman's life when menstrual periods become irregular. Refers to the time near menopause. [NIH] Perinatal: Pertaining to or occurring in the period shortly before and after birth; variously defined as beginning with completion of the twentieth to twenty-eighth week of gestation and ending 7 to 28 days after birth. [EU] Periodicity: The tendency of a phenomenon to recur at regular intervals; in biological systems, the recurrence of certain activities (including hormonal, cellular, neural) may be annual, seasonal, monthly, daily, or more frequently (ultradian). [NIH] Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral Nerves: The nerves outside of the brain and spinal cord, including the autonomic, cranial, and spinal nerves. Peripheral nerves contain non-neuronal cells and connective tissue as well as axons. The connective tissue layers include, from the outside to the inside, the epineurium, the perineurium, and the endoneurium. [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 Neuropathy: Nerve damage, usually affecting the feet and legs; causing pain, numbness, or a tingling feeling. Also called "somatic neuropathy" or "distal sensory polyneuropathy." [NIH] Perivascular: Situated around a vessel. [EU] Perspiration: Sweating; the functional secretion of sweat. [EU] 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
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logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [EU] Pharmaceutical Preparations: Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form. [NIH] Pharmacodynamics: The study of the biochemical and physiological effects of drugs and the mechanisms of their actions, including the correlation of actions and effects of drugs with their chemical structure; also, such effects on the actions of a particular drug or drugs. [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] Phenyl: Ingredient used in cold and flu remedies. [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] Photophobia: Abnormal sensitivity to light. This may occur as a manifestation of eye diseases; migraine; subarachnoid hemorrhage; meningitis; and other disorders. Photophobia may also occur in association with depression and other mental disorders. [NIH] Photoreceptor: Receptor capable of being activated by light stimuli, as a rod or cone cell of the eye. [NIH] Phototherapy: Treatment of disease by exposure to light, especially by variously concentrated light rays or specific wavelengths. [NIH] Phototransduction: The transducing of light energy to afferent nerve impulses, such as takes place in the retinal rods and cones. After light photons are absorbed by the photopigments, the signal is transmitted to the outer segment membrane by the cyclic GMP second messenger system, where it closes the sodium channels. This channel gating ultimately generates an action potential in the inner retina. [NIH] Phrenic Nerve: The motor nerve of the diaphragm. The phrenic nerve fibers originate in the cervical spinal column (mostly C4) and travel through the cervical plexus to the diaphragm.
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[NIH]
Physical Therapy: The restoration of function and the prevention of disability following disease or injury with the use of light, heat, cold, water, electricity, ultrasound, and exercise. [NIH]
Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]
Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] 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] Placebo Effect: An effect usually, but not necessarily, beneficial that is attributable to an expectation that the regimen will have an effect, i.e., the effect is due to the power of suggestion. [NIH] Placebos: Any dummy medication or treatment. Although placebos originally were medicinal preparations having no specific pharmacological activity against a targeted condition, the concept has been extended to include treatments or procedures, especially those administered to control groups in clinical trials in order to provide baseline measurements for the experimental protocol. [NIH] Plague: An acute infectious disease caused by Yersinia pestis that affects humans, wild rodents, and their ectoparasites. This condition persists due to its firm entrenchment in sylvatic rodent-flea ecosystems throughout the world. Bubonic plague is the most common form. [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] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU] 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]
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Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]
Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polycystic: An inherited disorder characterized by many grape-like clusters of fluid-filled cysts that make both kidneys larger over time. These cysts take over and destroy working kidney tissue. PKD may cause chronic renal failure and end-stage renal disease. [NIH] 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] 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] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postoperative: After surgery. [NIH] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Post-traumatic: Occurring as a result of or after injury. [EU] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] 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] 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] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Prednisolone: A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states. [NIH] Prednisone: A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver. [NIH] Premenopausal: Refers to the time before menopause. Menopause is the time of life when a women's menstrual periods stop permanently; also called "change of life." [NIH] Preoptic Area: Region of hypothalamus between the anterior commissure and optic chiasm. [NIH]
Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] Presynaptic Terminals: The distal terminations of axons which are specialized for the release of neurotransmitters. Also included are varicosities along the course of axons which have similar specializations and also release transmitters. Presynaptic terminals in both the central and peripheral nervous systems are included. [NIH] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Prion: Small proteinaceous infectious particles that resist inactivation by procedures modifying nucleic acids and contain an abnormal isoform of a cellular protein which is a major and necessary component. [NIH] Private Practice: Practice of a health profession by an individual, offering services on a person-to-person basis, as opposed to group or partnership practice. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Problem Solving: A learning situation involving more than one alternative from which a selection is made in order to attain a specific goal. [NIH] 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]
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Prognostic factor: A situation or condition, or a characteristic of a patient, that can be used to estimate the chance of recovery from a disease, or the chance of the disease recurring (coming back). [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] 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] Proneness: Susceptibility to accidents due to human factors. [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] Proportional: Being in proportion : corresponding in size, degree, or intensity, having the same or a constant ratio; of, relating to, or used in determining proportions. [EU] 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] 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] Prosthesis: An artificial replacement of a part of the body. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. Quaternary protein structure describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). [NIH] Protein Isoforms: Different forms of a protein that may be produced from different genes, or from the same gene by alternative splicing. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH]
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Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Pruritic: Pertaining to or characterized by pruritus. [EU] Pruritus: An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. [NIH] Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] 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] Psychoneuroimmunology: The field concerned with the interrelationship between the brain, behavior and the immune system. Neuropsychologic, neuroanatomic and psychosocial studies have demonstrated their role in accentuating or diminishing immune/allergic responses. [NIH] Psychopathology: The study of significant causes and processes in the development of mental illness. [NIH] Psychophysiology: The study of the physiological basis of human and animal behavior. [NIH]
Psychosis: A mental disorder characterized by gross impairment in reality testing as evidenced by delusions, hallucinations, markedly incoherent speech, or disorganized and agitated behaviour without apparent awareness on the part of the patient of the incomprehensibility of his behaviour; the term is also used in a more general sense to refer to mental disorders in which mental functioning is sufficiently impaired as to interfere grossly with the patient's capacity to meet the ordinary demands of life. Historically, the term has been applied to many conditions, e.g. manic-depressive psychosis, that were first described in psychotic patients, although many patients with the disorder are not judged psychotic. [EU] Psychotherapy: A generic term for the treatment of mental illness or emotional disturbances primarily by verbal or nonverbal communication. [NIH] Psychotropic: Exerting an effect upon the mind; capable of modifying mental activity; usually applied to drugs that effect the mental state. [EU] Psychotropic Drugs: A loosely defined grouping of drugs that have effects on psychological function. Here the psychotropic agents include the antidepressive agents, hallucinogens, and tranquilizing agents (including the antipsychotics and anti-anxiety agents). [NIH]
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Ptosis: 1. Prolapse of an organ or part. 2. Drooping of the upper eyelid from paralysis of the third nerve or from sympathetic innervation. [EU] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]
Pulmonary: Relating to the lungs. [NIH] Pulmonary 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]
Pupil: The aperture in the iris through which light passes. [NIH] Purifying: Respiratory equipment whose function is to remove contaminants from otherwise wholesome air. [NIH] Pustular: Pertaining to or of the nature of a pustule; consisting of pustules (= a visible collection of pus within or beneath the epidermis). [EU] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Quaternary: 1. Fourth in order. 2. Containing four elements or groups. [EU] 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] Radial Artery: The direct continuation of the brachial trunk, originating at the bifurcation of the brachial artery opposite the neck of the radius. Its branches may be divided into three groups corresponding to the three regions in which the vessel is situated, the forearm, wrist, and hand. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radioactive: Giving off radiation. [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays,
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gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] Radius: The lateral bone of the forearm. [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] Randomized clinical trial: A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] 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] Reassurance: A procedure in psychotherapy that seeks to give the client confidence in a favorable outcome. It makes use of suggestion, of the prestige of the therapist. [NIH] Rebound effect: The characteristic of a drug to produce reverse effects when either the effect of the drug has passed, or when the patient no longer responds to the drug. [EU] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Receptors, Serotonin: Cell-surface proteins that bind serotonin and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. [NIH] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Recovery Room: Hospital unit providing continuous monitoring of the patient following anesthesia. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recur: To occur again. Recurrence is the return of cancer, at the same site as the original (primary) tumor or in another location, after the tumor had disappeared. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Red Nucleus: A pinkish-yellow portion of the midbrain situated in the rostral mesencephalic tegmentum. It receives a large projection from the contralateral half of the
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cerebellum via the superior cerebellar peduncle and a projection from the ipsilateral motor cortex. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Regression Analysis: Procedures for finding the mathematical function which best describes the relationship between a dependent variable and one or more independent variables. In linear regression (see linear models) the relationship is constrained to be a straight line and least-squares analysis is used to determine the best fit. In logistic regression (see logistic models) the dependent variable is qualitative rather than continuously variable and likelihood functions are used to find the best relationship. In multiple regression the dependent variable is considered to depend on more than a single independent variable. [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] Relaxant: 1. Lessening or reducing tension. 2. An agent that lessens tension. [EU] Relaxation Techniques: The use of muscular relaxation techniques in treatment. [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] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Renal pelvis: The area at the center of the kidney. Urine collects here and is funneled into the ureter, the tube that connects the kidney to the bladder. [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] Resection: Removal of tissue or part or all of an organ by surgery. [NIH] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Respirator: A mechanical device that helps a patient breathe; a mechanical ventilator. [NIH] Respiratory failure: Inability of the lungs to conduct gas exchange. [NIH] Respite Care: Patient care provided in the home or institution intermittently in order to provide temporary relief to the family home care giver. [NIH] Restless legs: Legs characterized by or showing inability to remain at rest. [EU]
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Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Reticular: Coarse-fibered, netlike dermis layer. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [NIH] Retrospective: Looking back at events that have already taken place. [NIH] Retrospective study: A study that looks backward in time, usually using medical records and interviews with patients who already have or had a disease. [NIH] 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] Rhythmicity: Regular periodicity. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Rod: A reception for vision, located in the retina. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Saponins: Sapogenin glycosides. A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycon moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics
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when injected into the blood stream able to dissolve red blood cells at even extreme dilutions. [NIH] Sarcoma: A connective tissue neoplasm formed by proliferation of mesodermal cells; it is usually highly malignant. [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] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Scrapie: A fatal disease of the nervous system in sheep and goats, characterized by pruritus, debility, and locomotor incoordination. It is caused by proteinaceous infectious particles called prions. [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] Secobarbital: A barbiturate that is used as a sedative. Secobarbital is reported to have no anti-anxiety activity. [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] 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] 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] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH]
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Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Sertraline: A selective serotonin uptake inhibitor that is used in the treatment of depression. [NIH]
Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Sex Determination: The biological characteristics which distinguish human beings as female or male. [NIH] 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] Shivering: Involuntary contraction or twitching of the muscles. It is a physiologic method of heat production in man and other mammals. [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] Sign Language: A system of hand gestures used for communication by the deaf or by people speaking different languages. [NIH] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH]
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Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Sleep apnea: A serious, potentially life-threatening breathing disorder characterized by repeated cessation of breathing due to either collapse of the upper airway during sleep or absence of respiratory effort. [NIH] Sleep 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 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] Social Work: The use of community resources, individual case work, or group work to promote the adaptive capacities of individuals in relation to their social and economic environments. It includes social service agencies. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Sodium Channels: Cell membrane glycoproteins selective for sodium ions. Fast sodium current is associated with the action potential in neural membranes. [NIH] Solitary Nucleus: Gray matter located in the dorsomedial part of the medulla oblongata associated with the solitary tract. The solitary nucleus receives inputs from most organ systems including the terminations of the facial, glossopharyngeal, and vagus nerves. It is a major coordinator of autonomic nervous system regulation of cardiovascular, respiratory, gustatory, gastrointestinal, and chemoreceptive aspects of homeostasis. The solitary nucleus is also notable for the large number of neurotransmitters which are found therein. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU]
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Soma: The body as distinct from the mind; all the body tissue except the germ cells; all the axial body. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Soporific: 1. Causing or inducing profound sleep. 2. A drug or other agent which induces sleep. [EU] Spasm: An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. [NIH] Spasticity: A state of hypertonicity, or increase over the normal tone of a muscle, with heightened deep tendon reflexes. [EU] Spatial disorientation: Loss of orientation in space where person does not know which way is up. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Squamous: Scaly, or platelike. [EU] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Squamous cells: Flat cells that look like fish scales under a microscope. These cells cover internal and external surfaces 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] Status Epilepticus: Repeated and prolonged epileptic seizures without recovery of consciousness between attacks. [NIH] Steel: A tough, malleable, iron-based alloy containing up to, but no more than, two percent
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carbon and often other metals. It is used in medicine and dentistry in implants and instrumentation. [NIH] Sterilization: The destroying of all forms of life, especially microorganisms, by heat, chemical, or other means. [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] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] 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] Stupor: Partial or nearly complete unconsciousness, manifested by the subject's responding only to vigorous stimulation. Also, in psychiatry, a disorder marked by reduced responsiveness. [EU] Subacute: Somewhat acute; between acute and chronic. [EU] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Subliminal: Below the threshold of sensation, as a subliminal stimulus. [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]
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Sumatriptan: A serotonin agonist that acts selectively at 5HT1 receptors. It is used in the treatment of migraines. [NIH] Support group: A group of people with similar disease who meet to discuss how better to cope with their cancer and treatment. [NIH] Supportive care: Treatment given to prevent, control, or relieve complications and side effects and to improve the comfort and quality of life of people who have cancer. [NIH] Suppositories: A small cone-shaped medicament having cocoa butter or gelatin at its basis and usually intended for the treatment of local conditions in the rectum. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Suprachiasmatic Nucleus: An ovoid densely packed collection of small cells of the anterior hypothalamus lying close to the midline in a shallow impression of the optic chiasm. [NIH] Supraspinal: Above the spinal column or any spine. [NIH] 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] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Synapses: Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate through direct electrical connections which are sometimes called electrical synapses; these are not included here but rather in gap junctions. [NIH] 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] Systemic: Affecting the entire body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tachycardia: Excessive rapidity in the action of the heart, usually with a heart rate above 100 beats per minute. [NIH] Tardive: Marked by lateness, late; said of a disease in which the characteristic lesion is late in appearing. [EU]
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Telangiectasia: The permanent enlargement of blood vessels, causing redness in the skin or mucous membranes. [NIH] Telencephalon: Paired anteriolateral evaginations of the prosencephalon plus the lamina terminalis. The cerebral hemispheres are derived from it. Many authors consider cerebrum a synonymous term to telencephalon, though a minority include diencephalon as part of the cerebrum (Anthoney, 1994). [NIH] Temazepam: A benzodiazepinone that acts as a GABA modulator and anti-anxiety agent. [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] Terminator: A DNA sequence sited at the end of a transcriptional unit that signals the end of transcription. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Thalamic: Cell that reaches the lateral nucleus of amygdala. [NIH] Thalamic Diseases: Disorders of the centrally located thalamus, which integrates a wide range of cortical and subcortical information. Manifestations include sensory loss, movement disorders; ataxia, pain syndromes, visual disorders, a variety of neuropsychological conditions, and coma. Relatively common etiologies include cerebrovascular disorders; craniocerebral trauma; brain neoplasms; brain hypoxia; intracranial hemorrhages; and infectious processes. [NIH] Thalamus: Paired bodies containing mostly gray substance and forming part of the lateral wall of the third ventricle of the brain. The thalamus represents the major portion of the diencephalon and is commonly divided into cellular aggregates known as nuclear groups. [NIH]
Thalidomide: A pharmaceutical agent originally introduced as a non-barbiturate hypnotic, but withdrawn from the market because of its known tetratogenic effects. It has been reintroduced and used for a number of immunological and inflammatory disorders. Thalidomide displays immunosuppresive and anti-angiogenic activity. It inhibits release of tumor necrosis factor alpha from monocytes, and modulates other cytokine action. [NIH] Theophylline: Alkaloid obtained from Thea sinensis (tea) and others. It stimulates the heart and central nervous system, dilates bronchi and blood vessels, and causes diuresis. The drug is used mainly in bronchial asthma and for myocardial stimulation. Among its more prominent cellular effects are inhibition of cyclic nucleotide phosphodiesterases and antagonism of adenosine receptors. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] 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] Thoracic: Having to do with the chest. [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]
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Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]
Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] 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]
Tin: A trace element that is required in bone formation. It has the atomic symbol Sn, atomic number 50, and atomic weight 118.71. [NIH] Tinnitus: Sounds that are perceived in the absence of any external noise source which may take the form of buzzing, ringing, clicking, pulsations, and other noises. Objective tinnitus refers to noises generated from within the ear or adjacent structures that can be heard by other individuals. The term subjective tinnitus is used when the sound is audible only to the affected individual. Tinnitus may occur as a manifestation of cochlear diseases; vestibulocochlear nerve diseases; intracranial hypertension; craniocerebral trauma; and other conditions. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tonic: 1. Producing and restoring the normal tone. 2. Characterized by continuous tension. 3. A term formerly used for a class of medicinal preparations believed to have the power of restoring normal tone to tissue. [EU] Tonicity: The normal state of muscular tension. [NIH] Tooth Injuries: Traumatic or other damage to teeth including fractures (tooth fractures) or displacements (tooth luxation). [NIH] Tooth Loss: The failure to retain teeth as a result of disease or injury. [NIH] Topical: On the surface of the body. [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] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH]
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Traction: The act of pulling. [NIH] Tranquilizing Agents: A traditional grouping of drugs said to have a soothing or calming effect on mood, thought, or behavior. Included here are the anti-anxiety agents (minor tranquilizers), antimanic agents, and the antipsychotic agents (major tranquilizers). These drugs act by different mechanisms and are used for different therapeutic purposes. [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transdermal: Entering through the dermis, or skin, as in administration of a drug applied to the skin in ointment or patch form. [EU] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transferases: Transferases are enzymes transferring a group, for example, the methyl group or a glycosyl group, from one compound (generally regarded as donor) to another compound (generally regarded as acceptor). The classification is based on the scheme "donor:acceptor group transferase". (Enzyme Nomenclature, 1992) EC 2. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] 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]
Trees: Woody, usually tall, perennial higher plants (Angiosperms, Gymnosperms, and some Pterophyta) having usually a main stem and numerous branches. [NIH] Tremor: Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of cerebellar diseases, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of Parkinson disease. [NIH] Triazolam: A short-acting benzodiazepine used in the treatment of insomnia. Some countries temporarily withdrew triazolam from the market because of concerns about adverse reactions, mostly psychological, associated with higher dose ranges. Its use at lower doses with appropriate care and labeling has been reaffirmed by the FDA and most other countries. [NIH] 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] Trigger zone: Dolorogenic zone (= producing or causing pain). [EU] Trimipramine: Tricyclic antidepressant similar to imipramine, but with more antihistaminic
Dictionary 327
and sedative properties. [NIH] Trypanosomiasis: Infection with protozoa of the genus Trypanosoma. [NIH] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH] Tuberous Sclerosis: A rare congenital disease in which the essential pathology is the appearance of multiple tumors in the cerebrum and in other organs, such as the heart or kidneys. [NIH] Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Uraemia: 1. An excess in the blood of urea, creatinine, and other nitrogenous end products of protein and amino acids metabolism; more correctly referred to as azotemia. 2. In current usage the entire constellation of signs and symptoms of chronic renal failure, including nausea, vomiting anorexia, a metallic taste in the mouth, a uraemic odour of the breath, pruritus, uraemic frost on the skin, neuromuscular disorders, pain and twitching in the muscles, hypertension, edema, mental confusion, and acid-base and electrolyte imbalances. [EU]
Ureters: Tubes that carry urine from the kidneys to the bladder. [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] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Uvula: Uvula palatinae; specifically, the tongue-like process which projects from the middle of the posterior edge of the soft palate. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vacuoles: Any spaces or cavities within a cell. They may function in digestion, storage, secretion, or excretion. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH]
328 Insomnia
Vaginal: Of or having to do with the vagina, the birth canal. [NIH] Vaginitis: Inflammation of the vagina characterized by pain and a purulent discharge. [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] Valerian: Valeriana officinale, an ancient, sedative herb of the large family Valerianaceae. The roots were formerly used to treat hysterias and other neurotic states and are presently used to treat sleep disorders. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vascular Headaches: A group of disorders characterized by recurrent headaches associated with abnormal dilation and constriction of cerebral blood vessels. Representative disorders from this category include migraine, cluster headache, and paroxysmal hemicrania. [NIH] Vasculitis: Inflammation of a blood vessel. [NIH] Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [NIH] Vasodilatation: A state of increased calibre of the blood vessels. [EU] 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 oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Vertebrae: A bony unit of the segmented spinal column. [NIH] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Vestibular: Pertaining to or toward a vestibule. In dental anatomy, used to refer to the tooth surface directed toward the vestibule of the mouth. [EU] Vestibular Nerve: The vestibular part of the 8th cranial nerve (vestibulocochlear nerve). The vestibular nerve fibers arise from neurons of Scarpa's ganglion and project peripherally to vestibular hair cells and centrally to the vestibular nuclei of the brain stem. These fibers
Dictionary 329
mediate the sense of balance and head position. [NIH] Vestibule: A small, oval, bony chamber of the labyrinth. The vestibule contains the utricle and saccule, organs which are part of the balancing apparatus of the ear. [NIH] Vestibulocochlear Nerve: The 8th cranial nerve. The vestibulocochlear nerve has a cochlear part (cochlear nerve) which is concerned with hearing and a vestibular part (vestibular nerve) which mediates the sense of balance and head position. The fibers of the cochlear nerve originate from neurons of the spiral ganglion and project to the cochlear nuclei (cochlear nucleus). The fibers of the vestibular nerve arise from neurons of Scarpa's ganglion and project to the vestibular nuclei. [NIH] Vestibulocochlear Nerve Diseases: Diseases of the vestibular and/or cochlear (acoustic) nerves, which join to form the vestibulocochlear nerve. Vestibular neuritis, cochlear neuritis, and acoustic neuromas are relatively common conditions that affect these nerves. Clinical manifestations vary with which nerve is primarily affected, and include hearing loss, vertigo, and tinnitus. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Villous: Of a surface, covered with villi. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral Load: The quantity of measurable virus in the blood. Change in viral load, measured in plasma, is used as a surrogate marker in HIV disease progression. [NIH] Viroids: A group of pathogens comprising the smallest known agents of infectious disease. They are unencapsulated and are capable of replicating autonomously in susceptible cells. Positively identified viroids composed of single-stranded RNA have been isolated from higher plants, but the existence of DNA viroids pathogenic to animals is suspected. [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] Viscera: Any of the large interior organs in any one of the three great cavities of the body, especially in the abdomen. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Visceral Afferents: The sensory fibers innervating the viscera. [NIH] Vitreous Body: The transparent, semigelatinous substance that fills the cavity behind the crystalline lens of the eye and in front of the retina. It is contained in a thin hyoid membrane and forms about four fifths of the optic globe. [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] 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]
330 Insomnia
Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Xanthine: An urinary calculus. [NIH] 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] X-ray therapy: The use of high-energy radiation from x-rays to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. X-ray therapy is also called radiation therapy, radiotherapy, and irradiation. [NIH] Yawning: An involuntary deep inspiration with the mouth open, often accompanied by the act of stretching. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]
331
INDEX 5 5-alpha, 194, 255 A Abdomen, 255, 265, 266, 295, 305, 322, 324, 328, 329 Abdominal, 194, 255, 256, 272, 278, 305 Aberrant, 23, 64, 255, 272 Ablation, 45, 255 Acceptor, 173, 255, 305, 326 Acetaminophen, 219, 255 Acetylcholine, 182, 255, 270, 303 Acetylcholinesterase, 174, 255 Acidosis, 28, 255 Acne, 142, 190, 191, 255 Acoustic, 186, 187, 255, 329 Action Potentials, 182, 255 Acupuncture Analgesia, 114, 123, 255 Acupuncture Points, 173, 204, 209, 255 Acupuncture Therapy, 173, 255 Acyclovir, 202, 255 Adaptation, 255, 292, 303, 309 Adenine, 256 Adenosine, 16, 63, 256, 261, 267, 308, 324 Adipocytes, 256, 294 Adjunctive Therapy, 192, 256 Adjuvant, 32, 194, 256, 284 Adolescence, 31, 256 Adrenal Cortex, 256, 275, 311 Adrenal Medulla, 256, 268, 282, 303 Adrenergic, 28, 256, 258, 259, 260, 279, 282, 298, 323 Adverse Effect, 13, 14, 180, 181, 220, 256, 293, 319 Aerobic, 12, 256, 305 Aerobic Exercise, 12, 256 Aerosol, 16, 256 Afferent, 256, 294, 308 Affinity, 45, 256, 257, 262, 320 Agar, 257, 309 Aggravation, 71, 257 Aggressiveness, 7, 257 Agonist, 28, 34, 36, 193, 257, 263, 266, 279, 300, 323 Agranulocytosis, 190, 257 Airway, 4, 109, 257, 320 Airway Resistance, 4, 109, 257 Akathisia, 257, 260 Albumin, 185, 257, 309
Alertness, 7, 15, 16, 17, 55, 101, 170, 184, 257, 267 Algorithms, 257, 265 Alimentary, 183, 257, 292, 306 Alkaline, 255, 257, 267, 272 Alkaloid, 257, 266, 271, 299, 305, 324 Alleles, 257, 288 Allergen, 257, 277 Alpha Particles, 257, 314 Alpha-1, 258 Alternative medicine, 67, 218, 258 Alternative Splicing, 34, 258, 312 Amenorrhea, 258, 259 Amine, 258, 288 Amino Acid Sequence, 258, 259, 283, 285 Amino Acids, 152, 174, 258, 272, 285, 302, 307, 310, 312, 317, 327 Amitriptyline, 188, 258 Amnesia, 139, 258 Amphetamine, 258, 259 Amygdala, 15, 53, 258, 263, 295, 324 Amyloid, 185, 258 Anaesthesia, 258, 291 Anal, 30, 136, 259, 295 Analeptic, 173, 259 Analgesic, 193, 196, 255, 259, 266, 271, 299, 304 Analog, 43, 191, 255, 259 Anatomical, 53, 259, 262, 265, 270, 290, 318 Anemia, 233, 259, 287, 296 Anesthesia, 7, 117, 257, 259, 276, 315 Anesthetics, 259, 263, 282 Animal model, 15, 17, 35, 46, 95, 116, 259 Anions, 182, 257, 259, 292 Anode, 259 Anorexia, 24, 142, 172, 190, 259, 327 Anorexia Nervosa, 142, 172, 259 Antagonism, 25, 259, 267, 279, 324 Anthropometry, 50, 51, 52, 259 Anti-Anxiety Agents, 259, 313, 326 Antibacterial, 259, 321 Antibiotic, 152, 259, 307, 321 Antibodies, 259, 260, 262, 287, 288, 290 Antibody, 256, 260, 273, 287, 288, 290, 291, 293, 297, 299, 314, 315, 321, 330 Anticholinergic, 258, 260, 279 Anticoagulant, 260, 312 Anticonvulsant, 182, 192, 194, 260, 296
332 Insomnia
Antidepressant, 11, 64, 193, 219, 258, 260, 266, 284, 290, 298, 326 Antidepressive Agents, 260, 313 Antiemetic, 260, 278 Antiepileptic, 195, 260 Antigen, 54, 256, 259, 260, 273, 288, 289, 290, 291, 297 Anti-inflammatory, 255, 260, 262, 285, 311 Anti-Inflammatory Agents, 260, 262 Antimetabolite, 255, 260 Antioxidant, 27, 260 Antipsychotic, 9, 260, 302, 326 Antipyretic, 255, 261 Antispasmodic, 261, 304 Antitussive, 261, 278, 304 Antiviral, 255, 261 Anus, 259, 261, 266, 292 Anxiety Disorders, 14, 99, 174, 177, 178, 186, 187, 202, 261, 305 Anxiolytic, 182, 194, 195, 261 Apathy, 6, 200, 261, 302 Aperture, 261, 314 Apnea, 39, 46, 102, 145, 193, 236, 238, 251, 261 Apoptosis, 97, 261 Approximate, 20, 261 Aqueous, 16, 261, 263, 276, 281, 294 Arachidonic Acid, 261, 294 Arginine, 194, 261, 303 Aromatic, 261 Arrhythmia, 171, 261 Arterial, 63, 261, 289, 312, 323 Arteries, 261, 265, 266, 269, 275, 298 Arteritis, 4, 261 Articular, 261, 304 Arylsulfotransferase, 33, 261 Asphyxia, 179, 261 Aspirin, 171, 219, 262 Assay, 64, 262, 272, 290 Astringents, 262, 298 Astrocytes, 262, 299 Asymptomatic, 262, 305 Ataxia, 86, 232, 233, 262, 269, 324 Atrium, 262, 328 Atrophy, 232, 262, 302 Attenuated, 139, 262 Attenuation, 24, 262 Atypical, 4, 104, 178, 262 Audiology, 199, 210, 211, 262 Auditory, 136, 178, 262, 286, 297, 328 Aura, 183, 262
Auricular, 107, 114, 115, 121, 125, 131, 132, 139, 163, 262 Autoantibodies, 262, 277 Autodigestion, 262, 305 Autoimmune disease, 16, 262 Autonomic, 12, 67, 82, 186, 255, 261, 262, 263, 285, 303, 307, 320, 323 Autonomic Nervous System, 186, 263, 307, 320, 323 Autoradiography, 25, 263 Autosuggestion, 263, 290 B Baclofen, 35, 263 Bacteria, 180, 259, 260, 263, 274, 281, 283, 288, 296, 298, 299, 319, 321, 326, 327 Bactericidal, 263, 282 Bacteriophage, 263, 309, 326 Barbiturate, 188, 189, 263, 318, 324 Basal Ganglia, 63, 260, 262, 263, 266, 270, 284, 289, 295 Basal Ganglia Diseases, 262, 263, 270, 289 Basal metabolic rate, 16, 263 Base, 38, 53, 171, 191, 256, 263, 267, 276, 277, 284, 285, 293, 324, 327 Base Sequence, 263, 284, 285 Basophils, 257, 263, 286, 294 Behavior Therapy, 18, 76, 78, 79, 99, 123, 134, 135, 138, 140, 165, 201, 263 Behavioral Symptoms, 10, 263 Benign, 143, 264, 284, 287, 301, 314 Benzene, 264 Bereavement, 15, 30, 264 Beta-pleated, 258, 264 Bewilderment, 264, 274 Bibliotherapy, 36, 264 Bilateral, 16, 264, 306 Bile, 264, 284, 295, 322 Bile Acids, 264, 284, 322 Biliary, 264, 305 Biliary Tract, 264, 305 Bilirubin, 257, 264 Bioassay, 264 Bioavailability, 191, 264 Biochemical, 23, 38, 46, 257, 260, 264, 286, 294, 304, 308, 319 Biogenesis, 23, 264 Biological Assay, 186, 264 Biological Clocks, 23, 264 Biomarkers, 12, 27, 264 Biosynthesis, 23, 261, 265 Biotechnology, 68, 208, 218, 229, 231, 232, 233, 265
Index 333
Biotransformation, 261, 265 Bipolar Disorder, 191, 192, 236, 265 Bladder, 265, 270, 291, 312, 316, 327 Bloating, 4, 265, 291 Blood Cell Count, 265, 287 Blood Coagulation, 265, 267, 325 Blood Glucose, 214, 265, 287, 292 Blood Platelets, 265, 319 Blood pressure, 26, 35, 173, 198, 265, 268, 270, 289, 299, 303, 320 Blood vessel, 265, 268, 269, 270, 274, 281, 283, 293, 320, 322, 324, 325, 328 Blood-Brain Barrier, 192, 265 Blot, 47, 185, 265 Body Composition, 50, 51, 52, 265 Body Fluids, 264, 265, 279, 320, 327 Body Mass Index, 32, 265 Body Regions, 265, 272 Bone Density, 50, 51, 52, 174, 265 Bowel, 259, 266, 278, 322 Bowel Movement, 266, 278, 322 Brachial, 266, 314 Brachial Artery, 266, 314 Brachytherapy, 266, 292, 293, 314, 330 Bradykinin, 266, 303, 309 Brain Diseases, 8, 11, 266 Brain Stem, 266, 269, 328 Branch, 249, 266, 280, 297, 306, 314, 321, 324 Breakdown, 266, 278, 284 Bronchi, 266, 282, 324 Bronchial, 266, 288, 324 Bronchitis, 266, 271 Bronchoconstriction, 16, 266 Bronchus, 266 Bruxism, 238, 266, 320 Bulimia, 172, 266 Bullous, 266, 277 Buprenorphine, 173, 266 Bupropion, 63, 266 Burning Mouth Syndrome, 4, 266 C Caffeine, 63, 114, 171, 222, 253, 259, 267 Calcification, 63, 267 Calcitonin Gene-Related Peptide, 14, 267 Calcium, 45, 56, 119, 174, 267, 273, 299, 303, 305, 319 Candidiasis, 9, 267 Candidosis, 267 Canonical, 26, 267 Capsules, 175, 267, 284 Carbohydrate, 24, 214, 267, 286, 318
Carbon Dioxide, 267, 276, 284, 316 Carcinogenic, 264, 267, 291, 312, 322 Carcinogens, 268, 270, 304 Carcinoma, 267, 268 Cardiac, 267, 268, 280, 281, 282, 283, 300, 305, 322 Cardiorespiratory, 256, 268 Cardiotonic, 268, 278 Cardiovascular, 4, 12, 26, 39, 47, 62, 84, 258, 268, 294, 319, 320 Cardiovascular disease, 39, 268 Carotid Sinus, 172, 268, 285 Case report, 90, 140, 200, 268, 271 Case series, 74, 268, 271 Cataracts, 200, 268 Catechol, 261, 268 Catecholamine, 260, 268, 279, 308 Cations, 268, 292 Caudal, 268, 278, 289, 310 Causal, 47, 55, 268, 288, 292 Celiac Disease, 6, 268 Cell Death, 261, 268, 301 Cell Differentiation, 268, 319 Cell Division, 23, 232, 263, 269, 297, 299, 309, 312 Cell membrane, 23, 269, 270, 277, 308, 320 Cell proliferation, 269, 319 Cell Respiration, 269, 305, 316 Cellulose, 269, 284, 309 Central Nervous System, 46, 171, 177, 180, 181, 186, 192, 194, 197, 255, 258, 263, 264, 266, 267, 269, 270, 271, 284, 285, 287, 294, 299, 304, 307, 310, 319, 324 Central Nervous System Infections, 269, 287 Centrifugation, 269, 287 Cerebellar, 86, 262, 269, 316, 326 Cerebellar Diseases, 262, 269, 326 Cerebellum, 266, 269, 310, 316 Cerebral Arteries, 269, 299 Cerebral Palsy, 172, 269 Cerebrospinal, 44, 269 Cerebrospinal fluid, 44, 269 Cerebrovascular, 79, 263, 268, 269, 303, 324 Cerebrum, 269, 309, 324, 327 Cervical, 269, 308 Cervical Plexus, 269, 308 Character, 270, 276, 286 Chemoreceptor, 261, 270 Chemotherapy, 32, 92, 96, 173, 270, 274 Chloride Channels, 34, 270
334 Insomnia
Cholesterol, 143, 264, 270, 275, 322 Choline, 255, 270 Cholinergic, 42, 258, 260, 270 Cholinesterase Inhibitors, 10, 270 Chorea, 192, 197, 260, 270 Choreatic Disorders, 270 Choroid, 270, 317 Chromatin, 261, 270, 282, 303 Chromium, 193, 270 Chromosome, 270, 274, 286, 295 Chronic Disease, 36, 63, 270 Chronic Fatigue Syndrome, 79, 143, 271 Chronic Obstructive Pulmonary Disease, 19, 94, 143, 271 Chronic renal, 271, 310, 327 Chronobiology, 57, 271 Circadian, 12, 15, 17, 20, 21, 23, 24, 25, 26, 32, 38, 42, 44, 45, 46, 49, 55, 56, 57, 58, 62, 64, 66, 67, 78, 95, 116, 117, 125, 164, 170, 177, 184, 197, 271 CIS, 38, 271, 317 Clamp, 42, 271 Clinical study, 83, 128, 271, 275 Clone, 38, 64, 271 Cloning, 46, 265, 271 Coca, 271 Cocaine, 48, 253, 271 Cochlear, 271, 325, 329 Cochlear Diseases, 271, 325 Codeine, 219, 271, 304 Codon, 82, 272, 285 Coenzymes, 272, 303 Cofactor, 272, 312, 325 Cognition, 9, 12, 63, 189, 193, 210, 272, 302 Cognitive behavior therapy, 71, 100, 123, 272 Cognitive restructuring, 272, 322 Cognitive Therapy, 166, 272 Colic, 191, 192, 272 Collagen, 174, 272, 283, 284, 310, 312 Collapse, 266, 272, 320 Colloidal, 257, 272, 280 Combination Therapy, 28, 272 Comet Assay, 27, 272 Comorbidity, 53, 59, 219, 272 Complement, 272, 273, 285, 309 Complementary and alternative medicine, 121, 161, 273 Complementary medicine, 121, 273 Complete remission, 273, 316 Computational Biology, 229, 231, 273
Computed tomography, 50, 51, 52, 96, 265, 273 Computerized axial tomography, 273 Computerized tomography, 273 Concomitant, 180, 274, 302 Cone, 274, 308, 323 Confounding, 47, 60, 170, 274 Confusion, 6, 7, 213, 274, 278, 289, 302, 327 Congestion, 261, 274, 282 Conjugated, 37, 274 Conjugation, 261, 265, 274 Conjunctiva, 274, 326 Connective Tissue, 272, 274, 283, 284, 307, 317, 318 Consciousness, 259, 274, 276, 277, 279, 321 Consolidation, 173, 274 Consolidation therapy, 173, 274 Constipation, 117, 139, 200, 261, 274 Constriction, 194, 274, 293, 328 Consultation, 22, 274 Consumption, 39, 65, 66, 85, 274, 305 Continuous infusion, 25, 274 Continuum, 36, 182, 274 Contraindications, ii, 274 Control group, 11, 12, 19, 32, 41, 43, 58, 59, 67, 274, 309, 315 Controlled clinical trial, 32, 275 Controlled study, 95, 109, 110, 115, 130, 275 Conventional therapy, 275 Conventional treatment, 53, 275 Convulsion, 264, 275 Convulsive, 180, 181, 275 Coordination, 6, 269, 275 Cornea, 26, 275 Coronary, 19, 36, 268, 275, 298 Coronary heart disease, 268, 275 Coronary Thrombosis, 275, 298 Cortex, 35, 148, 262, 266, 269, 275, 283, 299, 316 Cortical, 172, 186, 197, 275, 283, 318, 324 Corticosteroids, 9, 219, 275, 285, 311 Cortisol, 24, 54, 58, 97, 164, 257, 275 Cortisone, 275, 311 Cranial, 172, 177, 178, 179, 183, 190, 191, 192, 269, 275, 285, 287, 292, 302, 304, 307, 326, 328, 329 Craniocerebral Trauma, 263, 275, 287, 324, 325 Cross Infection, 11, 275 Cues, 26, 184, 276 Curare, 276, 300
Index 335
Curative, 276, 303, 324 Cutaneous, 186, 267, 269, 276, 289, 294 Cyclic, 183, 267, 271, 276, 286, 303, 308, 318, 324 Cytokine, 194, 276, 324 Cytoplasm, 261, 263, 269, 276, 282, 286, 299, 303, 317 Cytotoxic, 276, 315, 319 D Dangerous Behavior, 10, 276 Data Collection, 15, 29, 276 Databases, Bibliographic, 229, 276 Decarboxylation, 276, 288 Degenerative, 11, 197, 276, 296, 300, 304 Dehydration, 5, 276 Deletion, 261, 276 Delirium, 10, 260, 276 Delivery of Health Care, 276, 287 Delusion, 9, 276 Dementia, 6, 7, 9, 10, 11, 65, 117, 172, 200, 202, 260, 277 Dendrites, 277, 302 Density, 50, 51, 52, 85, 174, 265, 269, 277, 304 Depersonalization, 277, 305, 318 Depolarization, 182, 277, 319 Depressive Disorder, 17, 59, 70, 277, 295 Deprivation, 4, 14, 33, 48, 277 Derealization, 277, 305 Dermal, 277, 294 Dermatitis, 190, 191, 277 Dermatitis Herpetiformis, 190, 191, 277 Dermatosis, 190, 191, 277 Desensitization, 66, 277 Detoxification, 24, 64, 277 Deuterium, 277, 289 Diabetes Mellitus, 172, 277, 285, 287, 307 Diagnostic procedure, 169, 218, 277 Dialyzer, 277, 287 Diaphoresis, 27, 277 Diaphragm, 172, 269, 278, 308 Diarrhea, 4, 27, 173, 278 Diastolic, 278, 289 Diencephalon, 278, 289, 324 Digestion, 48, 257, 264, 266, 278, 280, 291, 295, 322, 327 Digestive system, 168, 278 Digestive tract, 278, 320, 321 Digitalis, 171, 278 Dihydrotestosterone, 255, 278 Dilatation, 210, 278, 311 Dilation, 266, 278, 328
Dimethyl, 198, 278 Diphenhydramine, 126, 154, 278 Diploid, 278, 309 Direct, iii, 38, 47, 49, 185, 221, 272, 278, 279, 305, 314, 316, 323 Disease Progression, 8, 278, 329 Disease Transmission, 47, 278 Disease Transmission, Horizontal, 278 Disease Transmission, Vertical, 278 Disinfectant, 278, 282 Disorientation, 55, 186, 187, 274, 276, 278 Dissection, 88, 278 Dissociation, 256, 278 Distal, 279, 280, 284, 307, 311, 313 Diuresis, 16, 171, 267, 279, 324 Diurnal, 45, 279 Dizziness, 5, 187, 190, 279, 305 Dopamine, 62, 258, 260, 266, 271, 279, 299 Doxepin, 82, 188, 279 Dreams, 206, 209, 279 Drinking Behavior, 60, 279 Drive, ii, vi, 17, 62, 113, 279, 294 Drug Interactions, 223, 279 Drug Resistance, 279 Drug Tolerance, 23, 26, 279, 325 Duct, 279, 317 Duodenum, 264, 279, 305, 322 Dyes, 258, 263, 280, 303 Dyskinesia, 192, 260, 280 Dyspareunia, 27, 280 Dyspepsia, 280, 291 Dysphoric, 55, 277, 280 Dysplasia, 233, 280 Dyspnea, 280, 305 Dystonia, 260, 280 Dystrophy, 232, 280 E Eating Disorders, 172, 280 Effector, 184, 255, 273, 280, 302 Effector cell, 280, 302 Elastin, 272, 280 Elective, 280 Electrode, 177, 259, 280 Electroencephalography, 89, 103, 280 Electrolysis, 259, 268, 280 Electrolyte, 276, 280, 310, 320, 327 Electrons, 260, 263, 280, 292, 305, 314, 315 Electrophoresis, 47, 272, 280 Electrophysiological, 34, 42, 280 Embryo, 268, 281, 291 Emphysema, 271, 281 Empirical, 14, 28, 34, 57, 281
336 Insomnia
Emulsion, 263, 281 Encephalopathy, 47, 180, 185, 281 Endemic, 281, 296, 321 Endocarditis, 267, 281 Endocrine System, 281, 302 Endometrial, 27, 281 Endometrium, 281, 290, 298 Endothelial cell, 265, 281, 325 Endothelium, 281, 303 Endothelium-derived, 281, 303 Endotoxin, 281, 327 End-stage renal, 5, 271, 281, 310 Energy balance, 281, 294 Enhancer, 64, 187, 281 Environmental Exposure, 281, 304 Environmental Health, 228, 230, 281 Enzymatic, 48, 267, 273, 282, 288, 317 Enzyme, 23, 33, 255, 261, 272, 280, 282, 286, 295, 296, 299, 309, 312, 319, 325, 326, 329, 330 Eosinophils, 257, 282, 286, 294 Epidemic, 282, 321 Epidemiological, 11, 17, 27, 71, 282 Epidermal, 282, 294, 297 Epidermis, 282, 294, 314 Epidermoid carcinoma, 282, 321 Epinephrine, 54, 256, 279, 282, 303, 327 Erectile, 200, 282 Erection, 282 Erythema, 9, 282 Erythrina, 156, 159, 282 Erythrocytes, 259, 265, 282, 288 Escalation, 40, 282 Esophagus, 278, 282, 284, 287, 296, 308, 322 Essential Tremor, 232, 282 Estrogen, 62, 282 Ethanol, 40, 178, 185, 282 Eukaryote, 24, 282 Evacuation, 274, 282 Evoke, 186, 283, 322 Excitability, 182, 283, 301 Excitation, 28, 186, 270, 283 Excitatory, 25, 182, 263, 283, 285 Exhaustion, 259, 283, 296 Exogenous, 57, 184, 265, 283 Exon, 34, 258, 283 Expiration, 283, 316 Extensor, 283, 313 External-beam radiation, 283, 293, 314, 330 Extracellular, 34, 258, 262, 274, 283, 320
Extrapyramidal, 257, 260, 279, 283 Exudate, 283, 304 F Facial, 183, 283, 297, 306, 320 Facial Pain, 183, 283 Family Planning, 229, 283 Fat, 50, 51, 52, 256, 261, 265, 275, 283, 294, 295, 317 Fatigue, 4, 6, 9, 14, 18, 21, 32, 41, 43, 55, 56, 64, 81, 92, 208, 219, 252, 271, 283, 302 Fatty acids, 257, 283, 295 Feces, 274, 283, 322 Fibroblasts, 283, 292 Fibrosis, 23, 233, 283, 318 Flatus, 284 Flexor, 283, 284, 294 Fluoxetine, 11, 70, 284 Foramen, 270, 284, 297 Forearm, 265, 284, 314, 315 Frameshift, 34, 284 Friction, 257, 284 Fungus, 267, 284 G Gallbladder, 255, 264, 278, 284 Ganglia, 255, 263, 284, 301, 307, 323 Ganglion, 284, 304, 328, 329 Gas, 4, 267, 284, 289, 291, 303, 316, 328 Gas exchange, 284, 316, 328 Gastric, 171, 262, 284, 287, 288 Gastrin, 284, 288 Gastroesophageal Reflux, 4, 284 Gastrointestinal, 55, 183, 191, 192, 266, 270, 282, 284, 294, 296, 301, 319, 320, 322, 327 Gastrointestinal tract, 270, 282, 284, 294, 319, 327 Gelatin, 175, 284, 323 Gene, 23, 26, 33, 36, 37, 38, 46, 64, 66, 82, 88, 180, 208, 233, 234, 257, 258, 265, 267, 284, 285, 304, 309, 312 Gene Expression, 23, 26, 33, 38, 233, 285 Genetic Code, 285, 303 Genetic Engineering, 265, 271, 285 Genetic Markers, 66, 285 Genetics, 33, 53, 87, 88, 98, 274, 285, 307 Genomics, 38, 285 Genotype, 285, 308 Geriatric, 7, 36, 65, 71, 84, 102, 105, 110, 116, 128, 190, 201, 285 Gestation, 285, 307 Gestures, 285, 319 Ginseng, 149, 152, 155, 158, 159, 285
Index 337
Gland, 256, 275, 285, 305, 306, 312, 318, 322, 325 Glossopharyngeal Nerve, 172, 283, 285 Glucocorticoid, 285, 311 Glucose, 213, 232, 265, 269, 270, 277, 285, 286, 287, 289, 291, 292, 317 Glucose Intolerance, 277, 285 Glutamate, 46, 285, 298 Glutamic Acid, 189, 192, 285, 312 Gluten, 268, 286 Glycogen, 171, 286 Glycopeptides, 48, 286 Glycoprotein, 286, 294, 325, 327 Glycosylation, 48, 286 Goats, 286, 318 Gonad, 286 Gonadal, 57, 286, 322 Governing Board, 286, 311 Graft, 286, 288, 290 Granule, 286, 317 Granulocytes, 257, 286, 319 Growth, 27, 65, 176, 232, 256, 259, 261, 268, 269, 286, 292, 296, 301, 304, 309, 318, 327 Guanylate Cyclase, 286, 303 H Habitual, 17, 173, 270, 286 Habituation, 173, 199, 286 Hair Cells, 286, 328 Half-Life, 28, 187, 286 Hallucinogens, 286, 313 Haploid, 286, 309 Haptens, 256, 287 Headache, 4, 173, 176, 181, 183, 190, 210, 220, 241, 267, 287, 289, 328 Headache Disorders, 4, 183, 287 Health Care Costs, 47, 287 Health Education, 49, 287 Health Expenditures, 287 Hearing aid, 199, 287 Heart attack, 200, 268, 287 Heartburn, 252, 287, 291 Hematocrit, 32, 265, 287 Hemicrania, 287, 328 Hemodialysis, 90, 277, 287, 293 Hemoglobin, 32, 259, 265, 282, 287 Hemoglobinuria, 232, 287 Hemolysis, 190, 288 Hemorrhage, 275, 287, 288, 308, 322 Hemostasis, 288, 319 Hepatic, 257, 276, 288 Hereditary, 270, 288, 300, 302, 317 Heredity, 284, 285, 288
Herpes, 241, 255, 288 Herpes Zoster, 288 Heterogeneity, 48, 87, 256, 288 Heterozygotes, 62, 288 Histamine, 16, 260, 278, 279, 288, 298 Histidine, 288 Holidays, 10, 288 Homeostasis, 33, 288, 320 Homogeneous, 274, 288 Homologous, 257, 288, 323 Hormonal, 25, 47, 62, 262, 264, 288, 307 Hormone Replacement Therapy, 57, 60, 61, 83, 288 Host, 40, 60, 61, 180, 263, 267, 288, 290, 294, 329 Hybrid, 20, 64, 271, 288 Hybridomas, 288, 292 Hydrogen, 190, 255, 258, 263, 267, 277, 289, 299, 302, 304, 307, 313 Hydrolysis, 255, 265, 289, 295, 308, 310 Hydroxylamines, 261, 289 Hydroxylysine, 272, 289 Hydroxyproline, 272, 289 Hyperphagia, 24, 27, 289 Hyperplasia, 27, 143, 289, 294 Hypersensitivity, 257, 277, 278, 289, 294, 317 Hypertension, 27, 144, 171, 268, 289, 292, 327 Hypertrophy, 289 Hypesthesia, 289, 302 Hypnotherapy, 130, 289 Hypoglycaemia, 276, 289 Hypoglycemia, 171, 172, 213, 289 Hypokinesia, 179, 190, 191, 192, 289, 306 Hypotension, 194, 261, 289 Hypothalamic, 17, 57, 62, 77, 289 Hypothalamus, 25, 37, 57, 184, 255, 263, 266, 278, 289, 295, 311, 323, 324 Hypoxia, 276, 289, 324 Hysteria, 208, 289 I Iatrogenic, 8, 11, 28, 290 Iatrogenic Disease, 8, 290 Id, 118, 141, 182, 237, 238, 240, 242, 248, 250, 290 Idiopathic, 136, 290 Imbedding, 114, 125, 290 Imipramine, 290, 326 Immune function, 32, 54, 97, 290 Immune response, 33, 256, 260, 262, 275, 287, 290, 322, 329
338 Insomnia
Immune system, 55, 216, 280, 290, 294, 300, 313, 327 Immunity, 54, 97, 129, 202, 290 Immunoassay, 185, 290 Immunodeficiency, 202, 232, 290 Immunodeficiency syndrome, 202, 290 Immunoglobulins, 185, 290, 309 Immunologic, 290, 315 Immunology, 256, 290 Immunotherapy, 277, 290 Impairment, 6, 9, 29, 49, 62, 71, 201, 252, 262, 264, 276, 280, 290, 298, 313 Implant radiation, 290, 292, 293, 314, 330 Implantation, 290 Impotence, 200, 282, 290, 305 In vitro, 25, 36, 46, 181, 264, 291 In vivo, 25, 36, 45, 64, 264, 291 Incompetence, 284, 291 Incontinence, 7, 9, 191, 192, 200, 291 Indicative, 203, 291, 306, 328 Indigestion, 176, 252, 291 Induction, 23, 33, 163, 260, 274, 291 Infarction, 275, 291, 298 Inflammation, 32, 174, 191, 192, 255, 257, 260, 261, 262, 266, 277, 283, 288, 291, 294, 298, 302, 305, 317, 328 Infusion, 25, 291 Ingestion, 4, 289, 291, 310 Inhalation, 256, 291, 310 Initiation, 54, 165, 167, 291, 326 Initiator, 264, 291 Inlay, 291, 317 Innervation, 37, 279, 291, 314 Inorganic, 77, 174, 291 Inositol, 291, 298, 318 Inotropic, 279, 291 Insight, 44, 54, 291 Institutionalization, 30, 65, 201, 292 Insulin, 4, 26, 213, 264, 292 Insulin-dependent diabetes mellitus, 292 Interleukin-6, 77, 292 Intermittent, 17, 18, 28, 41, 173, 292, 296 Internal radiation, 292, 293, 314, 330 Interstitial, 266, 292, 293, 316, 330 Intervention Studies, 41, 73, 292 Intestinal, 268, 292, 296 Intestines, 255, 283, 284, 292 Intoxication, 276, 292, 330 Intracellular, 23, 42, 45, 182, 267, 291, 292, 298, 303, 310, 315, 318, 319 Intracranial Hypertension, 287, 292, 325 Intramuscular, 292, 306
Intraocular, 33, 292 Intravenous, 187, 291, 292, 306 Intrinsic, 34, 42, 165, 171, 256, 292 Invasive, 290, 292 Involuntary, 172, 263, 270, 275, 282, 292, 300, 319, 320, 321, 330 Ion Channels, 42, 262, 292, 302 Ions, 182, 263, 270, 279, 280, 289, 292, 297, 320 Iris, 171, 275, 293, 314 Irradiation, 11, 114, 121, 293, 330 Ischemia, 192, 194, 262, 293 J Jealousy, 293, 305 Jet lag, 23, 133, 170, 217, 293 Joint, 27, 198, 261, 284, 293, 304, 320, 323 K Kava, 93, 116, 132, 138, 156, 206, 217, 293 Kb, 228, 293 Kidney Disease, 168, 228, 233, 293 Kidney Failure, 281, 293 Kidney stone, 4, 293 L Lag, 23, 55, 64, 144, 171, 293 Large Intestine, 278, 292, 293, 315, 320 Larynx, 293, 328 Latency, 8, 17, 44, 110, 178, 293 Least-Squares Analysis, 294, 316 Lectins, 282, 294 Leishmaniasis, 294, 307 Lens, 268, 294, 329 Leprosy, 190, 191, 294 Leptin, 24, 294 Lesion, 37, 294, 295, 319, 323 Leukemia, 202, 232, 294 Leukocytes, 27, 263, 265, 282, 286, 294, 299, 303, 327 Leukotrienes, 16, 261, 294 Libido, 200, 294 Library Services, 248, 294 Lichen Planus, 8, 294 Ligament, 294, 312 Ligands, 45, 294 Likelihood Functions, 294, 316 Limbic, 53, 63, 258, 295 Limbic System, 258, 295 Linear Models, 295, 316 Linkage, 24, 285, 295 Lipid, 270, 292, 295 Lipolysis, 171, 295 Lipoxygenase, 294, 295 Lithium, 260, 295
Index 339
Liver, 4, 26, 137, 255, 257, 261, 264, 278, 281, 283, 284, 286, 288, 295, 311 Localization, 46, 295 Localized, 102, 291, 294, 295, 309 Locomotion, 35, 295, 309 Locomotor, 45, 295, 318 Logistic Models, 295, 316 Longitudinal study, 46, 60, 61, 63, 295 Long-Term Care, 9, 53, 201, 296 Loop, 26, 157, 296 Lorazepam, 126, 222, 296 Lower Esophageal Sphincter, 284, 296 Luciferase, 26, 296 Lymphatic, 281, 291, 296 Lymphoid, 259, 275, 296 Lymphoma, 232, 296 M Macula, 296 Macula Lutea, 296 Macular Degeneration, 200, 296 Malabsorption, 232, 268, 296 Malaria, 190, 191, 296 Malaria, Falciparum, 296 Malaria, Vivax, 296 Malignant, 9, 232, 296, 301, 314, 318 Malingering, 10, 296 Malnutrition, 257, 262, 296, 300 Mammogram, 267, 296, 299 Mandible, 270, 297 Mania, 189, 191, 297 Manic, 26, 38, 95, 116, 260, 265, 295, 297, 313 Manic-depressive psychosis, 297, 313 Manifest, 17, 23, 24, 26, 297 Mastication, 297, 326 Maximum Tolerated Dose, 279, 297 Meatus, 297, 328 Mechanical ventilation, 28, 297 Mediate, 14, 38, 64, 279, 297, 329 Mediator, 297, 319 Medical Records, 9, 297, 317 MEDLINE, 229, 231, 233, 297 Meiosis, 297, 323 Melanocytes, 297 Melanoma, 232, 297 Membrane Glycoproteins, 297 Membrane Potentials, 182, 297 Memory, 6, 7, 23, 62, 147, 174, 190, 201, 204, 252, 258, 259, 276, 277, 297 Meninges, 269, 275, 298 Meningitis, 298, 308
Menopause, 4, 46, 60, 61, 62, 84, 128, 144, 200, 298, 307, 310, 311 Menstrual Cycle, 60, 61, 298, 311 Menstruation, 258, 298 Mental Disorders, 26, 31, 54, 65, 168, 201, 289, 298, 308, 313 Mental Health, iv, 12, 15, 20, 23, 30, 38, 49, 73, 165, 166, 168, 210, 228, 230, 239, 298, 314 Mental Processes, 279, 298, 313 Mental Retardation, 75, 234, 298 Mentors, 53, 298 Mercury, 77, 298 Mesolimbic, 260, 298 Meta-Analysis, 79, 108, 129, 133, 298 Metabolite, 265, 278, 298 Metabotropic, 46, 298 Methionine, 278, 298 MI, 190, 254, 298 Mianserin, 79, 298 Microbe, 298, 325 Microbiology, 256, 262, 299 Microcalcifications, 267, 299 Microorganism, 272, 299, 306, 329 Middle Cerebral Artery, 194, 299 Milliliter, 265, 299 Miscible, 195, 299 Mitosis, 261, 294, 299 Modeling, 30, 299 Modification, 115, 133, 170, 199, 285, 299, 314 Modulator, 36, 299, 324 Molecular, 23, 26, 33, 42, 46, 64, 87, 174, 229, 231, 265, 273, 299, 315, 326, 327 Molecule, 32, 36, 194, 260, 263, 273, 279, 280, 281, 283, 289, 299, 305, 315, 319, 328 Monitor, 3, 9, 60, 61, 177, 184, 299, 303 Monoamine, 62, 258, 260, 299 Monoclonal, 288, 293, 299, 314, 330 Monocytes, 292, 294, 299, 324 Mononuclear, 299, 327 Mood Disorders, 53, 57, 88, 200, 202, 299 Morphine, 28, 171, 193, 266, 271, 299, 301, 304 Morphological, 24, 281, 284, 297, 299 Motility, 209, 299, 319 Motion Pictures, 209, 300 Motion Sickness, 300, 301 Motor Activity, 62, 300 Motor nerve, 300, 308 Movement Disorders, 4, 260, 300, 324 Mucosa, 268, 300
340 Insomnia
Muscle Fibers, 300 Muscle relaxant, 4, 194, 219, 259, 300 Muscle Relaxation, 127, 140, 300 Muscle tension, 181, 195, 196, 300 Muscular Atrophy, 232, 300 Muscular Dystrophies, 280, 300 Musculature, 289, 300 Mutagenesis, 64, 300 Mutagens, 300 Myocardium, 298, 300 Myopathy, 4, 300 Myotonic Dystrophy, 232, 300 N Naive, 35, 300 Naloxone, 300 Naltrexone, 173, 300 Narcolepsy, 36, 37, 39, 41, 193, 197, 203, 207, 236, 237, 239, 241, 301 Narcosis, 301 Narcotic, 27, 173, 193, 299, 300, 301 Nasopharynx, 285, 301 Natural selection, 264, 301 Nausea, 4, 96, 173, 190, 260, 291, 301, 305, 327 NCI, 1, 168, 227, 271, 301, 307 Necrosis, 261, 291, 298, 301 Neonatal, 28, 301 Neonatal Abstinence Syndrome, 28, 301 Neoplasia, 232, 301 Neoplasm, 301, 318 Neoplastic, 283, 288, 296, 301 Nephropathy, 293, 301 Nerve Fibers, 255, 269, 301, 308, 328 Nervousness, 6, 58, 190, 203, 301 Networks, 45, 301 Neural, 11, 25, 75, 114, 184, 186, 199, 256, 258, 267, 301, 307, 320 Neuralgia, 4, 197, 302 Neurasthenia, 209, 210, 302 Neuritis, 190, 302, 329 Neurodegenerative Diseases, 8, 185, 263, 302 Neuroendocrine, 24, 96, 302 Neuroleptic, 257, 260, 302 Neurologic, 28, 259, 302 Neuromuscular, 255, 302, 327 Neuromuscular Junction, 255, 302 Neuronal, 37, 41, 45, 97, 182, 193, 198, 301, 302, 307 Neurons, 17, 37, 42, 45, 180, 182, 194, 197, 271, 277, 283, 284, 300, 301, 302, 323, 328, 329
Neuropathy, 4, 302, 307 Neuropeptide, 36, 64, 267, 302 Neurophysiology, 69, 70, 76, 82, 89, 107, 277, 302 Neurosis, 196, 302 Neurotic, 196, 259, 302, 328 Neurotic Disorders, 196, 302 Neurotransmitters, 182, 258, 261, 279, 302, 311, 320 Neutrons, 257, 293, 302, 314 Neutrophils, 257, 286, 294, 303 Niacin, 119, 303, 327 Night Blindness, 6, 303 Nimodipine, 56, 303 Nitric Oxide, 193, 303 Nitrogen, 257, 258, 303, 327 Nonmetastatic, 84, 303 Nonverbal Communication, 303, 313 Norepinephrine, 14, 26, 54, 256, 258, 279, 303 Nuclear, 46, 263, 274, 280, 282, 284, 295, 301, 303, 324 Nuclei, 184, 257, 258, 274, 280, 285, 295, 299, 302, 303, 304, 313, 328, 329 Nucleic acid, 180, 263, 285, 300, 303, 311 Nucleolus, 303, 317 O Ocular, 21, 32, 304 Odour, 136, 261, 304, 327 Oncogene, 232, 304 Opacity, 268, 277, 304 Opium, 28, 173, 299, 304, 305 Opportunistic Infections, 3, 202, 304 Optic Chiasm, 289, 304, 311, 323 Optic Nerve, 304, 317 Orofacial, 4, 283, 304 Orthostatic, 261, 304 Osmosis, 304 Osmotic, 25, 257, 304 Osteoarthritis, 36, 200, 304 Osteoporosis, 63, 144, 200, 304 Outpatient, 24, 80, 89, 114, 304 Ovum, 285, 290, 304, 311 Oxazepam, 83, 128, 158, 304 Oxidation, 27, 255, 260, 265, 304 Oxidative metabolism, 294, 305 Oxygen Consumption, 305, 316 P Pacemaker, 44, 64, 170, 184, 305 Palate, 285, 301, 305, 320, 327 Palliative, 75, 305, 324 Pancreas, 255, 264, 278, 292, 305, 327
Index 341
Pancreatic, 172, 232, 284, 305 Pancreatic cancer, 232, 305 Pancreatic Juice, 284, 305 Pancreatitis, 4, 305 Panic, 25, 142, 177, 187, 191, 192, 290, 305 Panic Disorder, 25, 177, 187, 290, 305 Papaverine, 304, 305 Paralysis, 276, 305, 306, 314 Paranoia, 7, 305 Parenteral, 196, 306 Paresis, 302, 306 Paresthesias, 302, 305, 306 Parkinsonism, 260, 306 Parotid, 285, 306 Paroxetine, 70, 193, 306 Paroxysmal, 232, 262, 287, 306, 328 Partial remission, 306, 316 Particle, 306, 326 Partnership Practice, 306, 311 Patch, 42, 306, 326 Pathogen, 185, 306 Pathogenesis, 8, 16, 33, 46, 47, 306 Pathologic, 87, 255, 261, 266, 267, 275, 289, 306, 313, 328 Pathologic Processes, 261, 306 Pathologies, 26, 306 Pathophysiology, 14, 19, 134, 306 Patient Education, 214, 240, 246, 248, 254, 306 Patient Satisfaction, 22, 109, 306 PDQ, 237, 306 Pelvic, 307, 312 Penicillin, 158, 259, 307 Pentamidine, 202, 307 Pentylenetetrazole, 25, 307 Peptide, 23, 34, 267, 294, 307, 310, 312 Perception, 19, 131, 195, 274, 277, 286, 307, 318 Perimenopausal, 57, 307 Perinatal, 179, 307 Periodicity, 307, 317 Peripheral blood, 27, 307 Peripheral Nerves, 294, 307 Peripheral Nervous System, 302, 307, 311, 322 Peripheral Neuropathy, 4, 307 Perivascular, 267, 307 Perspiration, 277, 307 PH, 96, 265, 307 Pharmaceutical Preparations, 269, 282, 284, 308 Pharmacodynamics, 28, 44, 187, 308
Pharmacokinetic, 13, 16, 82, 308 Pharmacologic, 5, 14, 25, 66, 97, 114, 124, 164, 214, 219, 259, 286, 308, 325 Pharmacotherapy, 5, 9, 28, 53, 79, 99, 104, 114, 124, 134, 135, 308 Pharynx, 284, 301, 308, 328 Phenotype, 42, 308 Phenyl, 175, 187, 194, 195, 197, 308 Phospholipases, 308, 319 Phospholipids, 283, 291, 308 Phosphorous, 48, 308 Phosphorus, 267, 308 Photophobia, 183, 308 Photoreceptor, 32, 308 Phototherapy, 308, 318 Phototransduction, 21, 33, 308, 318 Phrenic Nerve, 172, 308 Physical Therapy, 173, 309 Physiologic, 14, 170, 257, 265, 286, 289, 298, 302, 309, 315, 319, 326 Physiology, 23, 41, 58, 64, 78, 114, 117, 121, 139, 256, 280, 294, 302, 309, 328 Pigment, 64, 264, 297, 309 Pilot study, 13, 22, 41, 82, 115, 116, 117, 127, 309 Pineal Body, 309 Pineal gland, 44, 58, 62, 167, 185, 309 Placebo Effect, 122, 309 Placebos, 136, 309 Plague, 107, 309 Plants, 26, 33, 176, 184, 257, 264, 267, 270, 271, 278, 285, 303, 309, 317, 325, 326, 329 Plaque, 185, 309 Plasma, 13, 25, 58, 89, 181, 185, 187, 257, 259, 269, 284, 285, 287, 288, 293, 309, 318, 329 Plasma protein, 257, 309 Plasticity, 62, 309 Platelet Activation, 310, 319 Platelet Aggregation, 303, 310 Platelets, 303, 310 Platinum, 296, 310 Poisoning, 276, 292, 298, 301, 310 Polycystic, 233, 310 Polymorphism, 68, 82, 83, 88, 310 Polypeptide, 258, 272, 286, 310, 312, 330 Pons, 37, 266, 310 Pontine, 37, 310 Posterior, 259, 262, 269, 270, 285, 293, 305, 309, 310, 327 Postmenopausal, 77, 304, 310 Postoperative, 7, 310
342 Insomnia
Postsynaptic, 35, 182, 310, 319, 323 Post-translational, 34, 185, 310 Post-traumatic, 287, 300, 310 Potassium, 35, 297, 310 Potentiating, 258, 264, 310 Potentiation, 270, 310, 319 Practicability, 310, 326 Practice Guidelines, 10, 230, 240, 311 Precipitating Factors, 287, 311 Preclinical, 34, 311 Precursor, 261, 270, 279, 280, 282, 303, 311, 327 Prednisolone, 311 Prednisone, 9, 311 Premenopausal, 77, 311 Preoptic Area, 37, 311 Presynaptic, 182, 279, 311, 323 Presynaptic Terminals, 279, 311 Prevalence, 5, 6, 12, 17, 19, 31, 46, 50, 51, 52, 53, 60, 79, 89, 100, 101, 195, 210, 217, 219, 311 Prion, 8, 11, 47, 68, 82, 83, 180, 185, 269, 311 Private Practice, 132, 311 Probe, 62, 177, 311 Problem Solving, 201, 311 Progesterone, 311, 322 Prognostic factor, 21, 312 Progression, 8, 15, 46, 259, 312 Projection, 303, 304, 312, 315 Proline, 272, 289, 312 Promoter, 26, 64, 176, 312 Proneness, 170, 312 Prophase, 312, 323 Prophylaxis, 197, 312 Proportional, 170, 306, 312 Prospective Studies, 40, 312 Prospective study, 31, 50, 51, 52, 295, 312 Prostate, 14, 144, 200, 232, 264, 312, 327 Prosthesis, 172, 312 Protease, 47, 272, 312 Protein C, 23, 36, 185, 257, 258, 263, 272, 312 Protein Conformation, 23, 258, 312 Protein Isoforms, 258, 312 Protein S, 23, 48, 208, 233, 265, 285, 312, 317 Protocol, 17, 28, 45, 58, 60, 61, 163, 167, 309, 313 Protons, 257, 289, 313, 314 Proximal, 194, 279, 311, 313 Pruritic, 277, 294, 313
Pruritus, 278, 313, 318, 327 Psoriasis, 193, 313 Psychic, 206, 294, 302, 313, 318 Psychomotor, 276, 302, 313 Psychoneuroimmunology, 54, 313 Psychopathology, 15, 59, 81, 313 Psychophysiology, 90, 126, 137, 313 Psychosis, 6, 10, 190, 260, 313 Psychotherapy, 81, 114, 116, 117, 125, 166, 201, 264, 272, 313, 315 Psychotropic, 8, 10, 313 Psychotropic Drugs, 8, 10, 313 Ptosis, 187, 314 Public Health, 18, 25, 34, 48, 49, 209, 230, 314 Public Policy, 229, 314 Publishing, 3, 49, 68, 199, 210, 314 Pulmonary, 117, 257, 265, 274, 293, 294, 314, 328 Pulmonary Artery, 265, 314, 328 Pulse, 6, 173, 187, 299, 314 Pupil, 173, 275, 278, 314 Purifying, 24, 314 Pustular, 190, 191, 314 Q Quaternary, 312, 314 R Race, 180, 181, 314 Radial Artery, 177, 314 Radiation, 186, 263, 281, 283, 292, 293, 314, 330 Radiation therapy, 283, 292, 293, 314, 330 Radioactive, 263, 286, 289, 290, 292, 293, 303, 314, 330 Radiolabeled, 293, 314, 330 Radiotherapy, 266, 293, 314, 330 Radius, 314, 315 Random Allocation, 315 Randomization, 39, 56, 65, 315 Randomized clinical trial, 14, 83, 94, 141, 315 Reagent, 296, 315 Reality Testing, 313, 315 Reassurance, 211, 315 Rebound effect, 110, 315 Receptors, Serotonin, 315, 319 Recombination, 274, 285, 315 Recovery Room, 7, 315 Rectum, 261, 266, 278, 284, 291, 293, 312, 315, 323 Recur, 9, 307, 315, 318
Index 343
Recurrence, 21, 173, 265, 271, 297, 307, 315, 318 Red Nucleus, 262, 315 Refer, 1, 272, 279, 288, 295, 296, 300, 302, 303, 313, 316, 328 Refraction, 316, 321 Regimen, 13, 21, 29, 173, 280, 308, 309, 316 Regression Analysis, 32, 41, 43, 316 Regurgitation, 284, 287, 316 Relapse, 22, 48, 53, 92, 217, 316 Relaxant, 305, 316 Relaxation Techniques, 6, 122, 147, 316 Reliability, 40, 103, 107, 316 Remission, 59, 265, 297, 315, 316 Renal failure, 276, 316 Renal pelvis, 293, 316 Research Design, 53, 316 Research Support, 67, 316 Resection, 58, 316 Respiration, 172, 261, 267, 270, 276, 299, 305, 316 Respirator, 297, 316, 328 Respiratory failure, 39, 316, 328 Respite Care, 200, 316 Restless legs, 5, 105, 116, 241, 316 Restoration, 17, 92, 309, 317 Reticular, 9, 317 Retina, 46, 184, 270, 294, 296, 304, 308, 317, 329 Retinal, 32, 274, 304, 308, 317 Retinoblastoma, 232, 317 Retrospective, 7, 8, 9, 95, 317 Retrospective study, 7, 95, 317 Rheumatic Diseases, 219, 317 Rheumatism, 317 Rheumatoid, 4, 8, 190, 191, 317 Rheumatoid arthritis, 4, 8, 190, 191, 317 Rhythmicity, 23, 32, 45, 57, 184, 317 Ribose, 256, 317 Ribosome, 37, 317 Rigidity, 198, 306, 309, 317 Risk factor, 10, 60, 62, 63, 101, 200, 295, 312, 317 Rod, 82, 96, 97, 102, 109, 271, 308, 317 S Saliva, 317 Salivary, 17, 278, 305, 317 Salivary glands, 278, 317 Saponins, 317, 322 Sarcoma, 190, 191, 318 Schizoid, 318, 330
Schizophrenia, 172, 181, 192, 197, 306, 318, 330 Schizotypal Personality Disorder, 277, 318, 330 Sclerosis, 71, 179, 232, 318 Scrapie, 8, 47, 180, 185, 318 Screening, 15, 33, 41, 63, 64, 73, 92, 271, 307, 318 Seasonal Affective Disorder, 26, 46, 59, 318 Secobarbital, 188, 189, 318 Second Messenger Systems, 302, 318 Secretion, 55, 58, 77, 97, 271, 288, 292, 307, 318, 327 Secretory, 23, 318, 323 Sedative, 35, 44, 61, 110, 182, 194, 195, 196, 258, 263, 272, 278, 290, 293, 296, 318, 327, 328 Seizures, 28, 172, 174, 180, 186, 187, 192, 276, 306, 318, 321 Semen, 147, 148, 150, 312, 318 Senile, 104, 117, 137, 174, 304, 318 Sequencing, 38, 48, 319 Serologic, 290, 319 Serotonin, 14, 75, 114, 193, 219, 258, 260, 284, 298, 306, 308, 315, 319, 323, 327 Sertraline, 53, 70, 193, 319 Serum, 28, 63, 164, 257, 272, 319, 327 Sex Characteristics, 256, 319, 324 Sex Determination, 233, 319 Shedding, 48, 319 Shivering, 173, 319 Shock, 194, 319, 326 Sign Language, 72, 319 Signal Transduction, 23, 46, 291, 319 Signs and Symptoms, 28, 316, 319, 327 Skeletal, 191, 192, 194, 270, 271, 276, 300, 319, 321 Skeleton, 293, 319, 320 Skull, 275, 320, 324 Sleep apnea, 4, 5, 36, 39, 41, 46, 49, 50, 51, 52, 61, 81, 99, 105, 172, 320 Sleep Bruxism, 4, 320 Sleep Deprivation, 4, 33, 39, 48, 63, 79, 83, 89, 165, 171, 188, 189, 204, 320 Small intestine, 279, 288, 292, 320 Smooth muscle, 267, 288, 299, 305, 320, 321, 322 Sneezing, 319, 320 Snoring, 4, 241, 252, 320 Social Environment, 200, 314, 320 Social Support, 201, 320, 322
344 Insomnia
Social Work, 201, 320 Sodium, 179, 188, 297, 308, 320 Sodium Channels, 308, 320 Solitary Nucleus, 263, 320 Solvent, 187, 264, 282, 304, 320 Soma, 219, 321 Somatic, 27, 65, 105, 109, 256, 285, 289, 295, 297, 299, 306, 307, 321, 328 Soporific, 167, 321 Spasm, 181, 196, 261, 275, 321 Spasticity, 172, 181, 192, 198, 263, 321 Spatial disorientation, 200, 279, 321 Specialist, 242, 278, 321 Species, 180, 185, 276, 278, 282, 288, 294, 296, 297, 299, 314, 321, 322, 327, 329, 330 Specificity, 36, 45, 256, 321 Spectrum, 10, 80, 98, 321 Spinal cord, 194, 255, 262, 263, 266, 269, 270, 284, 298, 301, 302, 307, 321, 323 Sporadic, 11, 86, 302, 317, 321 Squamous, 9, 282, 321 Squamous cell carcinoma, 9, 282, 321 Squamous cells, 321 Statistically significant, 11, 44, 321 Status Epilepticus, 179, 321 Steel, 271, 321 Sterilization, 11, 322 Steroid, 182, 275, 317, 322 Stimulant, 222, 258, 267, 288, 307, 322 Stomach, 5, 206, 210, 255, 262, 264, 278, 282, 284, 288, 292, 296, 301, 308, 320, 322 Stool, 291, 293, 322 Strand, 27, 272, 322 Stress management, 19, 55, 322 Stroke, 63, 145, 168, 179, 200, 228, 237, 238, 239, 268, 322 Stupor, 301, 322 Subacute, 291, 322 Subarachnoid, 287, 308, 322 Subclinical, 291, 318, 322 Subcutaneous, 194, 196, 256, 306, 322 Subliminal, 186, 187, 205, 322 Subspecies, 321, 322 Substance P, 298, 318, 322 Sumatriptan, 193, 323 Support group, 202, 323 Supportive care, 307, 323 Suppositories, 284, 323 Suppression, 194, 197, 323 Suprachiasmatic Nucleus, 25, 33, 44, 62, 323 Supraspinal, 263, 323
Sympathetic Nervous System, 16, 28, 263, 323 Sympathomimetic, 258, 279, 282, 303, 323 Symphysis, 270, 312, 323 Symptomatic, 259, 305, 323 Synapses, 270, 302, 323 Synapsis, 323 Synaptic, 62, 182, 319, 323 Systolic, 289, 323 T Tachycardia, 27, 190, 323 Tardive, 192, 260, 323 Telangiectasia, 233, 324 Telencephalon, 263, 324 Temazepam, 70, 175, 324 Temporal, 17, 18, 25, 33, 38, 106, 258, 287, 296, 297, 324 Temporal Lobe, 258, 324 Terminator, 272, 324 Testosterone, 57, 255, 324 Thalamic, 262, 324 Thalamic Diseases, 262, 324 Thalamus, 82, 266, 278, 295, 324 Thalidomide, 93, 324 Theophylline, 16, 160, 324 Therapeutics, 13, 16, 25, 126, 146, 182, 209, 223, 324 Third Ventricle, 289, 309, 324 Thoracic, 278, 324 Thorax, 255, 324, 328 Threshold, 25, 283, 289, 322, 324 Thrombin, 310, 312, 325 Thrombomodulin, 312, 325 Thrombosis, 312, 322, 325 Thyroxine, 257, 325 Time Management, 322, 325 Tin, 5, 307, 310, 325 Tinnitus, 145, 197, 199, 200, 210, 211, 325, 329 Tissue, 11, 23, 172, 256, 260, 262, 264, 265, 267, 274, 279, 280, 281, 282, 283, 284, 286, 289, 290, 292, 294, 296, 297, 300, 301, 302, 305, 307, 309, 310, 316, 317, 319, 321, 322, 325 Tolerance, 23, 25, 28, 34, 35, 66, 76, 194, 266, 285, 325 Tomography, 325 Tonic, 187, 268, 325 Tonicity, 280, 288, 325 Tooth Injuries, 320, 325 Tooth Loss, 200, 325 Topical, 262, 282, 325
Index 345
Toxic, iv, 173, 194, 264, 274, 276, 278, 281, 290, 302, 307, 325 Toxicity, 14, 27, 191, 192, 279, 297, 298, 325 Toxicology, 97, 192, 230, 325 Toxins, 174, 260, 291, 325 Trace element, 270, 325 Traction, 271, 326 Tranquilizing Agents, 313, 326 Transcription Factors, 64, 326 Transdermal, 187, 196, 326 Transduction, 23, 319, 326 Transfection, 265, 326 Transferases, 286, 326 Translational, 326 Transmitter, 42, 182, 255, 262, 279, 292, 297, 303, 323, 326 Trauma, 108, 179, 276, 301, 305, 326 Treatment Outcome, 53, 65, 74, 326 Trees, 282, 326 Tremor, 173, 306, 326 Triazolam, 8, 128, 160, 187, 326 Tricyclic, 258, 260, 279, 290, 326 Trigeminal, 4, 172, 197, 283, 326 Trigger zone, 261, 326 Trimipramine, 109, 188, 326 Trypanosomiasis, 307, 327 Tryptophan, 117, 272, 319, 327 Tuberculosis, 274, 327 Tuberous Sclerosis, 233, 327 Tumor marker, 264, 327 Tumor Necrosis Factor, 77, 194, 324, 327 Tyrosine, 279, 327 U Unconscious, 259, 290, 327 Uraemia, 305, 327 Ureters, 293, 327 Urethra, 312, 327 Urinary, 9, 17, 42, 270, 291, 327, 330 Urine, 39, 50, 51, 52, 54, 63, 265, 279, 287, 291, 293, 316, 327 Uterus, 269, 281, 290, 298, 311, 327 Uvula, 320, 327 V Vaccine, 256, 313, 327 Vacuoles, 11, 327 Vagina, 267, 298, 327, 328 Vaginal, 27, 328 Vaginitis, 267, 328 Vagus Nerve, 172, 320, 328 Valerian, 76, 82, 83, 93, 114, 115, 116, 125, 127, 128, 132, 138, 141, 160, 166, 217, 237, 328
Vascular, 10, 171, 193, 270, 281, 287, 291, 303, 328 Vascular Headaches, 193, 328 Vasculitis, 305, 328 Vasoconstriction, 282, 328 Vasodilatation, 268, 328 Vasodilator, 266, 267, 279, 288, 305, 328 Vasomotor, 60, 61, 328 Vector, 326, 328 Vein, 292, 303, 306, 328 Venous, 265, 312, 328 Ventilation, 328 Ventilator, 297, 316, 328 Ventral, 289, 310, 328 Ventricle, 258, 314, 323, 324, 328 Vertebrae, 321, 328 Vesicular, 62, 277, 288, 328 Vestibular, 186, 286, 328, 329 Vestibular Nerve, 186, 328, 329 Vestibule, 328, 329 Vestibulocochlear Nerve, 325, 328, 329 Vestibulocochlear Nerve Diseases, 325, 329 Veterinary Medicine, 229, 329 Villous, 268, 329 Viral, 54, 326, 329 Viral Load, 54, 329 Viroids, 180, 329 Virulence, 262, 264, 325, 329 Virus, 54, 202, 263, 269, 281, 285, 309, 326, 329 Viscera, 321, 329 Visceral, 263, 285, 294, 295, 328, 329 Visceral Afferents, 263, 285, 328, 329 Vitreous Body, 317, 329 Vitro, 329 Vivo, 329 Volition, 292, 329 W Wakefulness, 31, 36, 37, 42, 62, 184, 252, 276, 329 Weight Gain, 206, 318, 329 Withdrawal, 25, 27, 34, 35, 44, 48, 58, 66, 76, 102, 114, 125, 130, 142, 172, 173, 194, 196, 276, 301, 304, 330 X Xanthine, 16, 330 Xenograft, 259, 330 X-ray, 265, 273, 293, 296, 303, 314, 330 X-ray therapy, 293, 330 Y Yawning, 301, 330
346 Insomnia
Yeasts, 267, 284, 308, 330
Z Zymogen, 312, 330
Index 347
348 Insomnia
