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

PNEA A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES J AMES N. P ARK...

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PNEA A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES

J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS

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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 2003 by ICON Group International, Inc. Copyright 2003 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1

Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Apnea: 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: 0-597-83740-6 1. Apnea-Popular works. I. Title.

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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.

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

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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on apnea. 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 APNEA ...................................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Apnea .......................................................................................... 12 E-Journals: PubMed Central ....................................................................................................... 69 The National Library of Medicine: PubMed ................................................................................ 69 CHAPTER 2. NUTRITION AND APNEA........................................................................................... 113 Overview.................................................................................................................................... 113 Finding Nutrition Studies on Apnea......................................................................................... 113 Federal Resources on Nutrition ................................................................................................. 118 Additional Web Resources ......................................................................................................... 118 CHAPTER 3. ALTERNATIVE MEDICINE AND APNEA .................................................................... 121 Overview.................................................................................................................................... 121 National Center for Complementary and Alternative Medicine................................................ 121 Additional Web Resources ......................................................................................................... 126 General References ..................................................................................................................... 127 CHAPTER 4. DISSERTATIONS ON APNEA ...................................................................................... 129 Overview.................................................................................................................................... 129 Dissertations on Apnea.............................................................................................................. 129 Keeping Current ........................................................................................................................ 130 CHAPTER 5. CLINICAL TRIALS AND APNEA ................................................................................. 131 Overview.................................................................................................................................... 131 Recent Trials on Apnea.............................................................................................................. 131 Keeping Current on Clinical Trials ........................................................................................... 133 CHAPTER 6. PATENTS ON APNEA ................................................................................................. 135 Overview.................................................................................................................................... 135 Patents on Apnea ....................................................................................................................... 135 Patent Applications on Apnea ................................................................................................... 161 Keeping Current ........................................................................................................................ 195 CHAPTER 7. BOOKS ON APNEA ..................................................................................................... 197 Overview.................................................................................................................................... 197 Book Summaries: Federal Agencies............................................................................................ 197 Book Summaries: Online Booksellers......................................................................................... 199 The National Library of Medicine Book Index ........................................................................... 201 Chapters on Apnea..................................................................................................................... 202 CHAPTER 8. MULTIMEDIA ON APNEA .......................................................................................... 207 Overview.................................................................................................................................... 207 Bibliography: Multimedia on Apnea.......................................................................................... 207 CHAPTER 9. PERIODICALS AND NEWS ON APNEA ....................................................................... 209 Overview.................................................................................................................................... 209 News Services and Press Releases.............................................................................................. 209 Newsletters on Apnea ................................................................................................................ 214 Academic Periodicals covering Apnea ....................................................................................... 214 CHAPTER 10. RESEARCHING MEDICATIONS................................................................................. 217 Overview.................................................................................................................................... 217 U.S. Pharmacopeia..................................................................................................................... 217 Commercial Databases ............................................................................................................... 218 Researching Orphan Drugs ....................................................................................................... 219 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 223 Overview.................................................................................................................................... 223

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NIH Guidelines.......................................................................................................................... 223 NIH Databases........................................................................................................................... 225 Other Commercial Databases..................................................................................................... 228 The Genome Project and Apnea ................................................................................................. 228 APPENDIX B. PATIENT RESOURCES ............................................................................................... 233 Overview.................................................................................................................................... 233 Patient Guideline Sources.......................................................................................................... 233 Associations and Apnea ............................................................................................................. 239 Finding Associations.................................................................................................................. 240 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 243 Overview.................................................................................................................................... 243 Preparation................................................................................................................................. 243 Finding a Local Medical Library................................................................................................ 243 Medical Libraries in the U.S. and Canada ................................................................................. 243 ONLINE GLOSSARIES................................................................................................................ 249 Online Dictionary Directories ................................................................................................... 249 APNEA DICTIONARY ................................................................................................................. 251 INDEX .............................................................................................................................................. 333

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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 apnea is indexed in search engines, such as www.google.com or others, a nonsystematic 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 apnea, 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 apnea, 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 apnea. 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 apnea, 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 apnea. 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 APNEA Overview In this chapter, we will show you how to locate peer-reviewed references and studies on apnea.

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and apnea, 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 “apnea” (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: •

Maxillomandibular Advancement Surgery for Obstructive Sleep Apnea Syndrome Source: JADA. Journal of the American Dental Association. 133(11): 1489-1497. November 2002. Contact: Available from American Dental Association. ADA Publishing Co, Inc., 211 East Chicago Avenue, Chicago, IL 60611. (312) 440-2867. Website: www.ada.org. Summary: Although maxillomandibular advancement (MMA) surgery is highly successful, the indications for and staging of MMA in the treatment of obstructive sleep apnea syndrome (OSAS) have not been settled upon. In this article, the author presents a retrospective review of several published case series with inclusion criteria of 20 or more patients who underwent MMA and received documented preoperative and postoperative diagnostic polysomnography. Protocols of MMA as a primary versus

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secondary operation, with and without adjunctive procedures in a site-specific approach, are compared and discussed. As an extrapharyngeal operation that enlarges and stabilizes the entire velo-orohypopharyngeal airway, MMA, which can be safely combined with adjunctive nonpharyngeal procedures, may circumvent the staging dilemmas associated with multiple, less successful, segmental, invasive, pharyngeal procedures. In accordance with current goals and guidelines governing OSAS surgery, MMA does not need to be limited to severe OSAS cases as a last resort after other procedures have failed but, rather, is also indicated as an initial operation for veloorohypopharyngeal narrowing. The author concludes that the diagnosis and management of OSAS requires a multidisciplinary team approach, including a working relationship between the dentist and sleep physician. General dentists and dental specialists who participate in the management of snoring and OSAS cases should have some knowledge of basic sleep medicine. 5 figures. 1 table. 55 references. •

Heart in Uremia: Role of Hypertension, Hypotension, and Sleep Apnea Source: American Journal of Kidney Diseases. 38(4 Supplement 1): S38-S46. October 2001. Contact: Available from W.B. Saunders Company. Periodicals Department, 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452 or (407) 345-4000. Summary: Cardiovascular disease is the leading cause of morbidity (illness) and mortality (death) in patients with end stage renal (kidney) disease (ESRD). The causes of this morbidity and mortality include those usually found in the general population, those related to the uremic status, and those related to dialysis treatment. This article focuses on the specific roles of hypertension (high blood pressure), hypotension (low blood pressure), anemia (low levels of hemoglobin, the oxygen carrying parts of the blood), hypoalbuminemia (low levels of protein in the blood), malnutrition, dyslipidemia (unhealthy levels of fats in the blood), reactive C protein, calciumphosphate product, dialysis modalities (hemodialysis versus peritoneal dialysis), and hyperhomocysteinemia. The authors put special emphasis on hyperparathyroidism as a traditional toxin. The emergent role of sleep apnea has been confirmed in animal models as well as in humans studied using polysomnography. There are difficulties in diagnosing coronary disease, because angiography has some risks, is expensive, and should be reserved for patients having symptoms of heart failure, patients with diabetes mellitus, or patients entering a transplantation list. This allows patients with coronary disease to undergo revascularization (adding blood vessels) through coronary artery bypass (preferably) or percutaneous transluminal angioplasty. Patients for whom surgery is not appropriate should be treated using more traditional medical procedures. 2 figures. 1 table. 36 references.

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Treating Obstructive Sleep Apnea and Snoring: Assessment of an Anterior Mandibular Positioning Device Source: JADA. Journal of the American Dental Association. 131(6): 765-771. June 2000. Contact: Available from American Dental Association. ADA Publishing Co, Inc., 211 East Chicago Avenue, Chicago, IL 60611. Summary: Dental devices have been used to help manage snoring and obstructive sleep apnea, or OSA. This article reports on patients' compliance with and complications of long term use of an anterior mandibular positioning, or AMP, device. The device used was a custom made, two piece, full coverage, adjustable acrylic appliance, used nightly. The appliance advanced the mandible by 75 percent of the patient's maximum

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protrusive distance. The study sample included 65 consecutive patients with mild to moderate obstructive sleep apnea and snoring. Long term use (three years or more) of the AMP device in these patients was 51 percent (27 of 53 patients). Of the 53 responding patients, 40 percent reported jaw or facial muscle pain, 40 percent had occlusal changes, 38 percent reported tooth pain, 30 percent reported jaw joint pain, and 30 percent experienced xerostomia. Of the 27 long term AMP users, 22 rated themselves as being very satisfied and four as somewhat satisfied; one person was neither satisfied nor dissatisfied with the appliance. The authors conclude that with use of the AMP device, 40 percent of patients will develop some minor complications of jaw, mouth, or tooth pain, and approximately 26 percent of long term users might experience a painless but irreversible change in their occlusion. Annual follow up office visits with the dentist appear necessary for early detection of these changes. 4 figures. 23 references. •

Sleep Apnea in End-Stage Renal Disease Source: Seminars in Dialysis. 4(1): 52-58. January-March 1991. Summary: Information regarding the prevalence and diagnosis of sleep disorders in patients with renal disease is limited, but interest in such abnormalities has increased over the last several years. This article reviews the literature on sleep apnea in end-stage renal disease (ESRD). Topics include diagnosis, the prevalence of sleep apnea in ESRD, etiological considerations, and treatment interventions. The author stresses that effective diagnosis and treatment of sleep apnea are required by physicians if we are to continue to make headway in improving the quality of life for ESRD patients. 1 figure. 2 tables. 58 references.

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Obstructive Sleep Apnea: Its Relevance in the Care of Diabetic Patients Source: Clinical Diabetes. 20(3): 126-132. Summer 2002. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: Obstructive sleep apnea (OSA) is a common and frequently unrecognized disorders. OSA is often found in patients with obesity, diabetes, and cardiovascular disease, and there is growing evidence that sleep apnea is independently associated with increased cardiovascular morbidity (related disease or complications). This article reviews the presentation, diagnosis, and treatment of OSA and its related health risks. The authors discuss the proposed associations between OSA and diabetes and insulin resistance. The authors conclude that diabetes and OSA are common disorders that often coexist in the setting of shared risk factors and perhaps a similar metabolic environment. Currently, emphasis is being placed on identifying and treating modifiable cardiovascular risk factors, such as tobacco abuse, obesity, hyperglycemia, hypertension, and dyslipidemia. The authors stress that there is growing evidence that OSA should be added to this list. 2 tables. 68 references.

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Longitudinal Effect on Facial Growth After Tonsillectomy in Children with Obstructive Sleep Apnea Source: World Journal of Orthodontics. 3(1): 67-72. Spring 2002. Contact: Available from Quintessence Publishing Co., Inc. 551 Kimberly Drive, Carol Stream, Illinois 60188. (800) 621-0387. Website: www.quintpub.com. Summary: Obstructive sleep apnea syndrome (OSAS) is characterized by heavy snoring, significant increases in respiratory rate and inspiratory effort, and arousals and apnoic

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(cessation of breathing) episodes during sleep. This article reports on a study undertaken to study the longitudinal effect on the dentition and facial morphology of children with OSAS and enlarged tonsils who have undergone tonsillectomy (removal of the tonsils) to relieve the pharyngeal obstruction. The mean age of the 14 children in the experimental group was 5.7 years; there were matched controls without pharyngeal obstruction problems. Preoperative, 1 year postoperative, and 3 year postoperative analyses of several dentitional (teeth), facial, and breathing variables were done. The results showed significant differences for several dentitional and facial variables, despite the small number of children and the short observation time. The largest changes occurred during the first postoperative year, indicating that the obstruction of the airway had significantly impacted facial morphology and the dentition in young children. The authors conclude that normalization after relief of the obstruction occurred mostly during the first postoperative year. 12 figures. 20 references. •

Nocturnal Polyuria in Type 2 Diabetes: A Symptom of Obstructive Sleep Apnea Source: Diabetes Educator. 28(3): 424-434. May-June 2002. Contact: Available from American Association of Diabetes Educators. 100 West Monroe Street, 4th Floor, Chicago, IL 60603-1901. (312) 424-2426. Summary: Polyuria (excessive urination) and nocturia (getting up at night to urinate) in individuals with type 2 diabetes may be due to obstructive sleep apnea (OSA), a recently recognized etiology (cause) of excess nighttime urine production. This article reports on an exploratory study that examined the relationships among glucose control, OSA, and nocturnal urine production. A sample of community-dwelling older adults (20 nondiabetic subjects and 10 poorly controlled type 2 diabetes subjects) was recruited based on self-report of nocturia more than twice per night. Participants were monitored on a metabolic research unit for 24 hours to track intake and output, collect blood and urine samples, and conduct an overnight polysomnography sleep study. None of the subjects had fasting serum glucose levels above the renal threshold. OSA was found in 65 percent of subjects. Those with moderate or severe OSA had significantly greater overnight urine production than subjects without OSA. Subjects with type 2 diabetes and moderate or severe OSA had the highest nocturnal urine production. The authors conclude that the high incidence of undetected OSA in subjects with type 2 diabetes with nocturia suggests that nocturia, OSA, and type 2 diabetes frequently coexist and may be interrelated. The article concludes with a list of resources, including Internet, books, pamphlets, and professional contacts, for readers who want to obtain more information. 2 figures. 3 tables. 42 references.

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Improvement of Sleep Apnea in Patients with Chronic Renal Failure Who Undergo Nocturnal Hemodialysis Source: New England Journal of Medicine. 344(2): 102-107. January 11, 2001. Summary: Sleep apnea (defined as the absence of airflow for longer than 10 seconds; it usually interrupts sleep) is common in patients with chronic renal failure (CRF) and is not improved by either conventional hemodialysis of peritoneal dialysis. With nocturnal hemodialysis, patients undergo hemodialysis seven nights per week at home, while sleeping. This article reports on a study undertaken to investigate the role of nocturnal hemodialysis in correcting sleep apnea in patients with CRF. Fourteen patients who were undergoing conventional hemodialysis for four hours on each of three days per week underwent overnight polysomnography (a measurement of sleep). The patients were then switched to nocturnal hemodialysis for eight hours during each of six or

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seven nights a week. They underwent polysomnography again 6 to 15 months later on one night when they were undergoing nocturnal hemodialysis and on another night when they were not. The mean serum creatinine concentration (a measurement of kidney or replacement kidney function) was significantly lower during the period when the patients were undergoing nocturnal hemodialysis than during the period when they were undergoing conventional hemodialysis. The conversion from conventional hemodialysis to nocturnal hemodialysis was associated with a reduction in the frequency of apnea and hypopnea from 25 (plus or minus 25) to 8 (plus or minus 8) episodes per hour of sleep. This reduction occurred predominantly in seven patients with sleep apnea, in whom the frequency of episodes fell from 46 (plus or minus 19) to 9 (plus or minus 9) episodes per hour, accompanied by increases in the minimal oxygen saturation, transcutaneous partial pressure of carbon dioxide, and serum bicarbonate concentration. During the period when these seven patients were undergoing nocturnal hemodialysis, the apnea hypopnea index measured on nights when they were not undergoing nocturnal hemodialysis was greater than that on nights when they were undergoing nocturnal hemodialysis, but it still remained lower than it had been during the period when they were undergoing conventional hemodialysis. The authors conclude that nocturnal hemodialysis corrects sleep apnea associated with chronic renal failure. 2 figures. 4 tables. 22 references. •

Obstructive Sleep Apnea: A Case Report Source: Journal of the Tennessee Dental Association. 82(3): 48-51. Fall 2002. Contact: Available from Journal of the Tennessee Dental Association. 2104 Sunset Place, Nashville, TN 37212. E-mail: [email protected]. Summary: Sleep-disordered breathing is a spectrum of relatively common medical problems ranging from apnea to hypopnea to upper airway resistance syndrome. Apnea is the temporary cessation of airflow during sleep for 10 seconds or more, despite continued ventilatory effort. Hypopnea is a reduction of 25 percent in airflow followed by arousal or desaturation of two percent or more. Upper airway resistance syndrome (UARS) involves frequent arousals in response to increased respiratory effect as a result of upper airway narrowing without overt apnea or hypopnea. This article reviews obstructive sleep apnea (OSA), a problem showing up in 4 percent of American males and 2 percent of American females. The authors stress that the role of dentistry in diagnosing and treating OSA is significant given the profession's knowledge of cephalometric radiography, oral appliances, and orthognathic surgery. Topics include epidemiology, symptoms, diagnostic tests, classification, and treatment options. The case report describes a 32 year old white male whose chief complaints were inability to sleep, snoring, daytime hypersomnolence, lack of energy, inability to sustain exercise, and obesity. 7 figures. 10 references.

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Dental Side Effects of an Oral Device To Treat Snoring and Obstructive Sleep Apnea Source: Sleep. 22(2): 237-240. March 15, 1999. Contact: Available from American Sleep Disorders Association. 6301 Bandel Road, Suite 101, Rochester, MN 55901. (507) 529-0804. Summary: Snoring and obstructive sleep apnea (OSA) are common and related conditions with major social and health implication. These conditions can be treated successfully with dental devices that reposition the mandible (lower jaw). Despite wide use, side effects of these devices have not yet been systematically evaluated. This article reports on a study undertaken to evaluate the side effects of a mandibular advancement

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splint (MAS). The research consisted of a questionnaire survey and dental examination of a consecutive case series of patients treated with the MAS. Attempts were made to contact all 191 patients treated over a 5 year period in a dental outpatient clinic; all patients had snored loudly and habitually with or without OSA prior to treatment. Of 191 patients treated, 132 agreed to complete the questionnaire and 106 underwent examination. Of the 132 interviewed, patient and partner report indicated that the device was well tolerated and controlled snoring satisfactorily in 100 patients after 31 (plus or minus 18) months of use. Dental side effects were reported in 107 patients, although these were mostly minor, and only 10 patients ceased using the device because of them. Side effects included excessive salivation (40 patients), xerostomia (30 patients), temporomandibular joint pain (35 patients), dental discomfort (35 patients), myofacial discomfort (33 patients), and bite changes (16 patients). Of 106 patients examined, 30 had increased maximal opening and 76 had no change compared with pretreatment records. Temporomandibular joint noises were found in 9 patients, and occlusal changes in 15. None of these effects could be related to degree of opening or protrusion produced by the MAS. The authors conclude that dental side effects occur in a significant proportion of patients using the MAS. In most cases, these are minor and their importance must be balanced against the efficacy of the MAS in treating snoring and OSA. 1 appendix. 2 figures. 9 references. (AA-M). •

Dentistry's Role in the Management of Obstructive Sleep Apnea Source: Journal of the Greater Houston Dental Society. 71(4): 29-30. November 1999. Contact: Available from Greater Houston Dental Society. One Greenway Plaza, Suite 110, Houston, TX 77046. (713) 961-4337. Fax (713) 961-3617. E-mail: [email protected]. Website: www.ghds.com. Summary: Snoring may be one symptom of a potentially life threatening sleep related disorder known as obstructive sleep apnea (OSA). This article describes how the dental community is actively playing a role in understanding, managing, and treating OSA. OSA occurs when the pharyngeal airways, which include the tongue, palate, and pharynx, collapse during sleep. The authors outline the signs and symptoms, complications of the condition, diagnosis, treatment, use of oral appliances, and the effects of oral appliance therapy. Dentists may participate in the management of OSA patients by understanding OSA, recognizing the signs and symptoms, developing a relationship with the patient's physician or sleep specialist, and having resources and referrals available for patients. Diagnosis is based on the clinical signs and symptoms, physical examination, as well as head, neck, and oral examinations. Age and obesity are two significant predictors of OSA. The two most commonly used types of oral appliances used during sleep are the tongue retaining device and the mandibular (lower jaw) repositioning splint. 6 references.

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Sleep Apnea in Alzheimer's Patients and the Healthy Elderly Source: Scholarly Inquiry for Nursing Practice: An International Journal. 1(3): 221-235. 1987. Summary: The incidence of sleep apnea was explored in 80 elderly subjects. Through the use of several criteria, sleep apnea was found more frequently in Alzheimer's patients (n equals 24) than in healthy controls (n equals 56). Alzheimer's patients were also found to have a significantly higher proportion of apnea related to non-rapid eye movement than to rapid eye movement sleep. Apnea-positive Alzheimer's patients also had significantly more awake time during the course of the night. A significant positive correlation

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between apnea index and severity of dementia, as measured by the Blessed Dementia Rating Scale, was found for apnea-positive Alzheimer's patients (r equals 0.57, p less than.01) as well as for the entire sample of Alzheimer's patients (r equals 0.41, p less than.05). Neuropathological implications are discussed, as well as the implications for nursing practice. 37 references. (AA). •

Snoring and Obstructive Sleep Apnea From a Dental Perspective Source: CDA Journal. Journal of the California Dental Association. 26(8): 557-565. August 1998. Contact: Available from California Dental Association (CDA). 1201 K Street, Sacramento, CA 95814. (916) 443-0505. Summary: This article considers the problems of snoring and obstructive sleep apnea from a dental perspective. The author stresses the proper diagnosis and treatment of sleep related disorders are best handled via a team approach. This team may include a general dentist treating in conjunction with other sleep specialists. The author provides a dental overview of sleep related breathing disorders, including key definitions, an outline of a diagnostic protocol, a discussion of the factors involved in decision making, and a summary of the wide variety of treatment modalities. Treatment methods discussed include general behavioral measures, surgical approaches (tracheotomy, nasal reconstruction, uvulopalatopharyngoplasty, and orthognathic procedures), and dental appliances. The author concludes with recommendations for the dentist who wishes to play a role in both the recognition and treatment of sleep disorders. These include revising the standard medical questionnaires to include questions on sleep disorders and snoring, revising how the intraoral examination is done (to incorporate evaluation of the oropharyngeal airway, the tongue, the mandible, and the nasal airway), and working closely with other health care professionals. 2 tables. 36 references. (AA-M).

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Diagnosing and Comanaging Patients with Obstructive Sleep Apnea Syndrome Source: JADA. Journal of the American Dental Association. 131(8): 1178-1184. August 2000. Contact: Available from American Dental Association. ADA Publishing Co, Inc., 211 East Chicago Avenue, Chicago, IL 60611. Summary: This article discusses the diagnosis and management of patients with obstructive sleep apnea syndrome (OSAS), a common, but underdiagnosed, disorder that can be fatal. The disorder is characterized by repetitive episodes of complete or partial upper airway obstruction leading to absent or diminished airflow into the lungs. These episodes usually last 10 to 30 seconds and result in loud snoring, a decrease in oxygen saturation, and chronic daytime sleepiness and fatigue. The obstruction is caused by the soft palate, base of the tongue or both collapsing against the pharyngeal walls because of decreased muscle tone during sleep. Potentially fatal systemic illnesses frequently associated with this disorder include hypertension, pulmonary (lung) hypertension, heart failure, nocturnal cardiac dysrhythmias, myocardial infarction (heart attack), and ischemic stroke. The classic signs and symptoms of OSAS may be recognizable by dental practitioners. Common findings in the medical history include daytime sleepiness, snoring, hypertension, and type 2 diabetes mellitus. Common clinical findings include male gender, obesity, increased neck circumference, excessive fat deposition in the palate, tongue (macroglossia) and pharynx, a long soft palate, a small recessive mandible and maxilla, and calcified carotid artery atheromas on parnoramic and lateral cephalometric radiographs. After confirmation of the diagnosis

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by a physician, dentists can participate in management of the disorder by fabricating mandibular advancement appliances and performing surgical procedures that prevent recurrent airway obstruction. 6 figures. 43 references. •

Sleep Apnea in End Stage Renal Disease Source: ANNA Journal. American Nephrology Nurses Association Journal. 24(6): 645654. December 1997. Contact: Available from American Nephrology Nurses Association. Box 56, East Holly Avenue, Pitman, NJ 08071. (609) 256-2320. Summary: This article familiarizes nephrology nurses with the sleep apnea syndrome, a disorder that is characterized by repetitive episodes of the cessation of breathing (apneas) or diminished airflow (hypopneas) that occur during sleep, and is usually, although not always, associated with a reduction in the oxygen saturation of the blood. The author reviews risk factors, clinical features, diagnostic strategies, and treatments. The author also discusses recent research linking sleep apnea with end-stage renal disease (ESRD). In diagnosing sleep apnea syndrome, the total number of apneas and hypopneas that occur during a sleep period are usually added together and then divided by the number of hours spent sleeping to obtain a respiratory disturbance index (RDI). While disrupted sleep and daytime sleepiness are significant problems, cardiopulmonary abnormalities are also important complications associated with sleep apnea. Risk factors for sleep apnea include obesity, craniofacial abnormalities, male gender, certain medical illnesses, lifestyle factors (use of alcohol and central nervous system depressants, smoking, exposure to allergens), and cardiovascular diseases. The author reviews nine studies of ESRD and sleep apnea, all of which demonstrated that sleep apnea has a prominent presence in ESRD, that both hemodialysis and peritoneal dialysis patients are vulnerable to it, and that dialysis itself seems to have little effect on its clinical expression. These studies showed that the incidence of sleep apnea is most likely much higher in this group than in the general population, but they did not succeed in determining the exact prevalence of sleep apnea in chronic renal failure because of subject selection bias and small sample sizes. The author concludes that patients with ESRD who have symptoms related to sleep-wake problems should be evaluated. Treatment of a sleeping disorder thus revealed is likely to have a drastic impact on the quality of life experienced by these patients. 4 figures. 2 tables. 26 references. (AA-M).

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Practice Parameters for the Treatment of Snoring and Obstructive Sleep Apnea with Oral Appliances: An American Sleep Disorders Association Report Source: Sleep. 186(6): 511-513. 1995. Contact: Available from American Sleep Disorders Association. Standards of Practice Committee, 1610 14th Street, N.W., Suite 300, Rochester, MN 55901-2200. (507) 287-6006. Summary: This article presents clinical guidelines, reviewed and approved by the Board of Directors of the American Sleep Disorders Association (ASDA), that provide recommendations for the use of oral appliances for the treatment of snoring and obstructive sleep apnea (OSA). The authors note that the U.S. FDA has approved some of the available oral appliances for the treatment of snoring, with and without OSA, even though limited data from controlled studies supporting the effectiveness and safety of these devices have been published. After a background section briefly describing the problems and morbidity associated with snoring and OSA, the article presents recommendations in the following areas: diagnosis, treatment objectives,

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indications, follow-up, and appliance fitting. A brief recommendations for future research. 1 table. 3 references. •

conclusion

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addresses

Treating Obstructive Sleep Apnea: Can An Intraoral Prosthesis Help? Source: JADA. Journal of the American Dental Association. 126(4): 461-466. April 1995. Summary: This article reports on a study of the effectiveness of an intraoral airway maintenance prosthesis used to treat obstructive sleep apnea syndrome (OSAS). The author presents a review of the relevant literature, and then describes the materials and methods used in the study of five men who were diagnosed with OSAS. The author goes into some detail in his discussion of the cephalometric technique. The prosthesis, which can be constructed and modified easily by a dentist, significantly reduced the number of apneas per night and the syndrome's severity in the subjects studied. 4 figures. 1 table. 13 references. (AA-M).

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Obstructive Sleep Apnea Surgery: Genioglossus Advancement Revisited Source: Journal of Oral and Maxillofacial Surgery. 59(10): 1181-1184. October 2001. Contact: Available from W.B. Saunders Company. Periodicals Department, P.O. Box 629239, Orlando, FL 32862-8239. (800) 654-2452. Summary: This article reports on a study that evaluated the accuracy of a genioglossus advancement (GA) technique (rectangular window) to incorporate the genial tubercle or genioglossus muscle complex (GGC) in patients with obstructive sleep apnea. The prospective study consisted of 38 consecutive patients who underwent GA. All 38 pairs of genial tubercles were captured. Thirty-one patients had both bellies of the genioglossus muscle incorporated. Two patients had a complete belly and a partial (greater than 50 percent) belly of the muscle captured. Five patients had only a portion of both muscle bellies included. The incomplete incorporation of the muscles in the bone flap was caused by the limited lateral extension of the osteotomy beyond the genial tubercles. The causes of the limited lateral osteotomy extension included crowding of the lower incisors as well as the presence of elongated or medially angulated canine roots. The results of this study show that the rectangular osteotomy technique accurately captures the genial tubercles and enables an adequate amount of the genioglossus muscle to be incorporated and advanced. 6 figures. 15 references.

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Glossoptosis (Posterior Displacement of the Tongue) During Sleep: A Frequent Cause of Sleep Apnea in Pediatric Patients Referred for Dynamic Sleep Fluoroscopy Source: AJR (American Journal of Roentgenology). 175(6): 1557-1559. December 2000. Contact: Available from American Roentgen Ray Society. 44211 Slatestone Court, Leesburg, VA 20147-5109. (800) 438-2777 or (703) 729-3353. Fax (703) 729-4839. Email: [email protected]. Summary: This article reports on a study undertaken to evaluate the frequency of glossoptosis (posterior displacement of the tongue) as a cause of sleep apnea in pediatric patients referred for fluoroscopic sleep studies. The authors reviewed seventy consecutive dynamic fluoroscopic sleep studies performed to evaluate sleep apnea. All patients had been sedated and examined with lateral fluoroscopy during sleep. Anatomic changes in the airway were correlated with episodes of oxygen desaturation (lower levels of oxygen in the blood). Cases of glossoptosis, in which the tongue moved posteriorly during sleep and abutted the posterior pharynx (airway), resulting in airway obstruction and oxygen desaturation, were identified. Of the 70 sleep studies reviewed,

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glossoptosis was the cause of airway obstruction in 17 patients (24 percent). Mean age in these 17 patients was 3 years (range, 5 days to 13 years). Seven of the 17 children were younger than 1 year old. Only three patients had no underlying medical problems. Four patients had macroglossia (Down syndrome, n = 3; duplicated tongue, n = 1) as a cause and three patients had micro or retrognathia (small or receding jaw). Six patients had neuromuscular abnormalities. The authors conclude that glossoptosis was a cause of airway obstruction in 25 percent of pediatric patients referred for fluoroscopic sleep studies. Attention to this anatomic region is important when evaluating children with sleep apnea. 2 figures. 19 references. •

Sleep Apnea: A Serious Disorder Source: Access. 9(7): 32-36. August 1995. Contact: Available from American Dental Hygienists' Association (ADHA). 444 North Michigan Avenue, Chicago, IL 60611. (800) 243-2342 or (312) 440-8900; Fax (312) 4408929; E-mail: [email protected]; http://www.adha.org. Summary: This article, from a journal for dental hygienists, reviews the problem of sleep apnea and its precursor, snoring. Topics covered include the epidemiology of sleep apnea; obstructive sleep apnea (OSA); the symptoms of snoring and sleep apnea; the consequences of an OSA episode; central sleep apnea (CSA); the association of sleep apnea and hypertension; treatment options, including nonsurgical, nonpharmalogical interventions, pharmacological interventions, and surgical interventions; and the oral health care professional's responsibility with regard to sleep apnea. One sidebar describes the appliances that have received FDA clearance for the treatment of snoring. 18 references.

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

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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Project Title: A HIGH-THROUGHPUT ASSAY FOR GENETIC STUDIES OF SLEEP Principal Investigator & Institution: Heller, Horace Craig.; Professor and Chair; Biological Sciences; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-AUG-2002 Summary: Arousal states are a fundamental aspect of global nervous system function; yet, measures of sleep and wake are rarely performed in genetically altered mice due to the difficulty of EEG analysis. We propose to develop a high-throughput alternative to EEG recordings in mice that will greatly facilitate the measurement of sleep and wake. Our system utilizes a simple piezoelectric transducer comprising the flexible floor upon which the animal rests. Distension of the floor by respiratory or other movements produces electrical signals. During slow wave sleep, rhythmic breathing results in a consistent, regular pattern of electical signals. REM sleep produces a less consistent signal due to more irregular breathing, while wake produces a dramatically irregular pattern caused by a variety of movements. Therefore, all three vigilance states can be accurately determined. We have already validated this system in young rats. Since no surgery is required and the signal patterns are simpler than those produced by EEG, the technology to perform high-throughput phenotyping of arousal states will be relatively easy. An immediate test and use of our system will be to investigate genes that underlie sleep parameters. Twin studies, adoption studies, and the analysis of inbred strains of mice have demonstrated that variation in sleep related traits are largely determined by genotype. Specifically, we propose to validate our system in common inbred strains of mice by comparing our piezo recordings with traditional EEG recordings. Based on our prior EEG data, we expect to confirm large sleep differences between AKR/J and DBA/2J inbred strains. This will be followed by examination of AKD2F1 hybrids and AKXD recominant inbred lines. QTL analysis of these data should identify candidate loci that underlie the variability of sleep traits in these two strains. With this high throughput system we will also be able to examine large numbers of progeny from appropriate genetic crosses between these or other strains to confirm putative QTLs. This system also makes large scale screening of mutagenized mice far more feasible, and we will begin to examine such mice in the proposed study. In general, the project we propose will provide an important index of nervous system function, and specifically will allow genetic approaches towards understanding sleep and sleep disorders that would not be possible with existing technology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ABSOLUTE NEAR INFRARED BRAIN OXIMETER Principal Investigator & Institution: Michalos, Antonios; Iss, Inc. 1602 Newton Dr Champaign, Il 61822 Timing: Fiscal Year 2003; Project Start 12-SEP-2000; Project End 31-MAY-2005 Summary: (provided by applicant): Our goals in Phase I have been completed and showed the feasibility of our approach. We applied Near-Infrared Spectroscopy (NIRS), a non-invasive method and an affordable, portable, bedside technique for the diagnosis of the degree of the hypoxic insult in the brain, in sleep apnea, during daytime napping. It has been suggested that chronic, recurrent hypoxia during sleep leads to brain injury, which causes neuropsychological deficits and decline of cognitive function. Cerebrovascular accidents, including fatal strokes are not uncommon. Conventional polysomnography, a relatively expensive test, detects sleep apnea at various sleep stages and determines arterial oxygen saturation. However, current clinical methods do not provide information on brain oxygenation, which is important especially in subjects

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with preexisting anatomical or functional vascular pathology. NIRS enables continuous real-time measurements of changes in the hemoglobin oxygenation and blood volume, thus providing information on tissue oxygenation and hemodynamics. In Phase II we propose the development of a tool and the application of NIRS to determine cerebral hemodynamics during sleep, in association to overnight polysomnographic sleep studies. Our goal is the development of reliable, cost efficient instrumentation for early detection of cerebral hemodynamic abnormalities in sleep apnea, for the prevention of hypoxic cerebral morbidity and mortality. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ACTIVATION OF TONGUE MUSCLES IN OBSTRUCTIVE SLEEP APNEA Principal Investigator & Institution: Durand, Dominique M.; Professor; Biomedical Engineering; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2001; Project Start 01-FEB-2001; Project End 31-DEC-2004 Summary: adapted from applicant's abstract) This project aims to develop an experimental therapy for obstructive sleep apnea (OSA) using electrical stimulation of the hypoglossal nerve. The PI proposes to use a multi-channel stimulation technique for selective activation of portions of the hypoglossal nerve to activate individual tongue muscles selectively. Such stimulation might increase control over the tongue muscles and improve efficiency for electrical stimulation to remove pharyngeal obstruction. There are 3 aims to be tested in dogs. Aim 1 will determine the maximum muscle selectivity that can be obtained with a multi-contact electrode on the hypoglossal nerve. Aim 2 will evaluate the mechanical dilation of the airways due to selective stimulation. Aim 3 will determine the optimum electrode geometries and stimulation paradigms for airway dilation in chronic dogs. It is anticipated that the experimental delineation and validation of these methods will lead to a design of a neuroprosthetic device for the treatment of OSA. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ADVANCED AT-HOME SCREENING DEVICE FOR SLEEP APNEA Principal Investigator & Institution: Cooke, Arthur V.; Active Signal Technologies, Inc. 13025 Beaver Dam Rd Cockeysville, Md 21030 Timing: Fiscal Year 2001; Project Start 15-JUN-1999; Project End 31-AUG-2003 Summary: Active Signal Technologies proposes to further develop its self applied, electrodeless home monitoring device for sleep apnea with the ultimate goal of making clinical diagnosis available to a much larger population of sleep disorder patients than currently possible. Preliminary results from Phase I have shown that much of the diagnostically rich airflow information captured in the sleep lab with a nasal mask and pneumotachograph can be replicated using an unobtrusive external tracheal contact sensor. Because this flow data has such important ramifications, the present proposal is being directed primarily to optimizing the sensor to work uniformly across a wide variety of cervical morphometries, and building real-time signal processing routines to separate snore, obstruction sounds, etc, from the broadband "hiss" of pure air movement in the trachea. This specific focus recognizes the broad application potential of the breathing sensor, not only as a critical component for the home monitoring device and as an alternative to a mask in the sleep lab but also throughout the field of respiratory care. In addition, the sensor captures far more acoustic information than just quantitative tidal volume and qualitative flow patterns, and hence can be used to

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characterize obstruction, respiratory effort, etc. PROPOSED COMMERCIAL APPLICATIONS: With approximately 10 million people suffering from obstructive sleep apnea alone yet <250,000 being tested per year in sleep clinics, the AAMS has a huge potential market. The AAMS priced at $1000 provides the patient with a costeffective, accurate screening option in the comfort of his or her home. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: AGE, GENDER, SEROTONIN AND RESPIRATORY CONTROL Principal Investigator & Institution: Behan, Mary; Professor; Comparative Biosciences; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2001; Project Start 15-AUG-2001; Project End 31-JUL-2004 Summary: Serotonin (5HT) plays a major role in breathing and the control of upper airway function. The proposed research will test the hypothesis that, with increasing age, there is a gender- specific decrease in serotonergic modulation of respiratory motoneurons. Because of gender-related differences, aging males may be uniquely susceptible to breathing disorders such as obstructive sleep apnea. Our preliminary data indicate that 5HT immunoreactivity in the hypoglossal nucleus decreases with age in male rats, but increases with age in female rats. Furthermore, long term facilitation, a 5HT-dependent increase in respiratory motor output following intermittent hypoxia, decreases to older male rats, but increases to older female rats. This is the first description of age-associated change in serotonergic modulation of respiratory control, and the first description of sexual dimorphism in age-related changes in any aspect of the serotonergic nervous system. The proposed research will test the hypothesis that gonadal hormones have a neuroprotective role in the maintenance of serotonergic modulation of respiratory motoneurons in female rats with increasing age, and can potentially reverse or delay the age-associated changes that occur in male rats. Five specific aims are proposed, each corresponding to a testable hypothesis. First, we will use neurochemical and anatomical assays to detect age- and gender- related changes in key elements of the serotonergic neuromodulatory system (5HT, 5HT receptors, and the serotonin reuptake transport protein) in hypoglossal and phrenic motor nuclei. Secondly, we propose to determine if there are functional consequences of aging and gender on respiratory responses to hypoxia in awake rats. Thirdly, we will test the hypothesis that serotonin-dependent components of the hypoxic ventilatory response are decreased selectively with aging in male rats. Finally, we propose to investigate the influence of neutering and hormone replacement therapy (estrogen, progesterone, testosterone) on our anatomical and physiological indices of serotonergic modulation of respiration in male and female rats. To our knowledge, this is the first proposal to study age and gender effects on any form of plasticity in respiratory control. An understanding of these mechanisms may lead to therapeutic strategies for intervention in age-related breathing disorders that affect both men and women such as obstructive sleep apnea. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: AGING, PROJECTIONS

EPISODIC

HYPOXIA,

AND

VAGAL

CARDIAC

Principal Investigator & Institution: Cheng, Zixi; Pediatrics; University of Louisville University of Louisville Louisville, Ky 40292 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2008

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Summary: (provided by applicant): Aging and the syndrome of obstructive sleep apnea, which is characterized by chronic intermittent hypoxia (CIH), are commonly associated with increased incidence and severity of hypertension, orthostatic intolerance, and cardiovascular diseases. However, our understanding of the neural mechanisms underlying these dysfunctions is impeded by a lack of structural information on autonomic nerve terminals and the circuitry within the cardiac tissues. Vagal projections to the heart originate from a sensory ganglion, i.e., the nodose ganglion, and the motor neuron pools in the brainstem, i.e., the nucleus ambiguus (NA) and the dorsal motor nucleus of the vagus (DmnX). The overall goal of the present application is to determine the functional deficits of the vagal control of the heart induced by aging, CIH, or both, and to identify the damage to the cardiac neural circuitry, specifically to the vagal axonal projections to the heart. Vagal control of particular cardiac functions will be measured in young (3months), middle age (12months) and aged (24 months) Fischer 344 rats. The vagal cardiac axons and terminals, and glutamatergic transmission within the NA and DmnX will be examined qualitatively and quantitatively using a battery of techniques that will include anterograde neural tracing, stereological counting, confocal microscopy, Neurolucida digitization, and dual immunohistochemistry. These anatomical findings will be assessed in conjunction with physiological responses to enhance our understanding of structure-function relationships. Aim 1 will assess agingassociated attenuation of baroreflex and vagal control of the heart, and the associated structural changes of vagal projections to the heart and aortic arch. Aim 2 will evaluate CIH-induced reduction of baroreflex sensitivity and vagal controls and the parallel vagal cardiac axon degeneration. Aim2 will also determine whether aging and CIH interact to induce more severe functional and anatomical damage to the vagal cardiac axons. Aim 3 will study changes in glutamatergic transmission within the caudal brainstem complex (NTS, NA, DmnX) during aging and following CIH. Collectively, the proposed experiments will advance our knowledge of brain-heart interactions and provide unique insights into the remodeling of vagal outflow to cardiac tissues during aging and following CIH. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ALZHEIMER CAREGIVER COPING: MENTAL AND PHYSICAL HEALTH Principal Investigator & Institution: Grant, Igor; Professor & Executive Vice Chairman; Psychiatry; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 92093 Timing: Fiscal Year 2001; Project Start 30-SEP-1997; Project End 31-AUG-2006 Summary: The experiences of elderly caregivers of Alzheimer relatives (CG) can be viewed as a model of chronic human stress in aging. Our work in the past funding cycle has been guided by the notion that such stress is accompanied by increased sympathoadrenalmedullary (SAM) activation whose cardiovascular and molecular responses may be amplified by superimposed stressors such as excessive care demands relative to respite received ("vulnerable CG"). The results to date indicate heightened basal circulating epinephrine (E) in vulnerable CG, altered L-selectin cell adhesion molecule (CAM) expression, down- regulation of beta-adrenergic receptors of lymphocytes, but no systematic changes in heart rate or blood pressure variability. Vulnerable CG who received a two week respite intervention demonstrated lessened circulating E in response to stressors compared to wait-listed CG, but there were no systematic treatment-related changes in other variables. Pilot data revealed: 1) increased expression of procoagulation factors (especially D-Dimer) which correlated with amount

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of sleep disturbance and level of catecholamines; 2) Vulnerable CG had less total sleep time and more awakenings than nonvulnerable CG. In the proposed research we wish to refine our understanding of the molecular changes underlying chronic and acute stress in elderly caregiving. The basic theory is that the chronic stress of caregiving yields a state of relative SAM arousal reflected in greater resting and stressor-related releases of catecholamines. As outcome variables of chronic and acute stressors related to caregiving, we shall focus on coagulation factors and cellular adhesion molecules, each of which has been associated with heightened risk of cardiovascular morbidity and mortality. The general hypothesis is that elderly caregivers, versus noncaregiving controls (NC) will have greater SAM arousal and greater expression of coagulation and adhesion molecules. It is posited further that those caregivers who have background medical risks (history of cardiovascular disease or hypertension), and who experienced superimposed stressors, such as excessive caregiving demands, or other negative life events, will be selectively vulnerable to these physiological changes. Disturbed sleep environment is posited to be one of the pathways whereby caregiving stressors are translated into SAM arousal and molecular changes. The study design calls for recruitment of 120 elderly caregivers (CG) and 60 noncaregiving controls (NC). Laboratory-derived speech stressor tasks will be used to probe differences in SAM responsivity to speech stressors between CG and NC, as well as CG at several levels of "mismatch" between caregiving demand and respite received. At-home polysomnography and actigraphy will monitor sleep disruption, sleep disorders (e.g., sleep apnea), and circadian activity variation. In the longitudinal phase, subjects will be re-evaluated annually to determine if hypothesized recovery of SAM arousability occurs in those CG who have placed their spouse, or whose spouse has died. The results of this research should bring us closer to understanding the physiological and molecular mechanisms underlying increased morbidity in elderly persons under chronic stress. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ANDROGENS PATHOPHYSIOLOGY

&

SLEEP:

APNEA

EPIDEMIOLOGY

&

Principal Investigator & Institution: Fogel, Robert B.; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2001; Project Start 01-AUG-2000; Project End 31-JUL-2005 Summary: (Adapted from the applicant's abstract) Obstructive sleep apnea (OSA) is a common disorder with important consequences for afflicted individuals. This disorder is characterized by recurrent pharyngeal collapse during sleep with subsequent repetitive arousals, along with substantial hypoxia and hypercapnia. Associated consequences include daytime somnolence, decreased performance on cognitive and vigilance testing and decreased quality of life. In addition, there is also increasing evidence that OSA may lead to adverse cardiovascular outcomes such as hypertension, arrhythmias, myocardial infarction and stroke. The pathophysiology of sleep apnea is dependent upon a complex interaction between upper airway anatomy, pharyngeal dilator muscle function and ventilatory control mechanisms, and the effects of state related changes in these variables. Substantial literature indicates that this disorder is much more common in men than in women, and that androgens in both men and women can exacerbate the disorder. However, neither the true extent of the effect of androgens on sleep apnea incidence and severity, nor the mechanisms by which androgens predispose to apnea have been well delineated to this point. With the proposed Mentored Patient-Oriented Research Career Development Award, the applicant will build upon his prior experiences investigating the role of androgens in the

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pathophysiology of sleep apnea. Based upon very positive experiences in the laboratory to date, the applicant is firmly committed to a career in academic pulmonary and critical care medicine, focused primarily on clinical research. The laboratory of Dr. David P. White at the Brigham and Women's Hospital will provide a rich intellectual environment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: APNEA DETECTION SYSTEM FOR NICU MONITORING Principal Investigator & Institution: Krausman, David T.; Vice Prsident & Ceo; Individual Monitoring Sys, Inc. (Im Sys) 1055 Taylor Ave, Ste 300 Baltimore, Md 21286 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 31-JAN-2004 Summary: (Applicant's abstract): Sleep apnea or sleep disordered breathing (SDA) occurs commonly among patients who have a stroke and may significantly complicate post-stroke recovery. SDB can be effectively treated and yet this treatment is not made available to patients on neurological intensive care units (NICU) owing to the problems of organizing requisite materials and expertise. Thus, the patients fail to get the needed treatment at the most critical recovery time when treatment would probably be the most beneficial. This project seeks to correct this problem by developing and apnea detection and reporting (ADR) system for use with existing monitoring equipment on the NICU. This system provides for easy, rapid identification of SDB events permitting starting treatment, if needed, shortly after entry to the NICU. The system provides data storage, convenient display and printouts of events and event rates. It uses technology developed by IM Systems for accurate recording and automatic detection of events. The system will automatically alert the staff when excessive SDB events occur. Phase 1 develops a prototype and evaluates its accuracy. Phase 2 improves the design and extends the use of system to a wide range of patients in the NICU. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: APPLES: APNEA POSITIVE PRESSURE LONG-TERM EFFICACY STUDY Principal Investigator & Institution: Dement, William C.; L W & J Q Berry Professor of Psychiatry; Psychiatry and Behavioral Sci; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-JUL-2007 Summary: (provided by applicant): Nasal continuous positive airway pressure (CPAP) therapy is in widespread use as the primary treatment for the obstructive sleep apnea syndrome (OSAS), a sleep-related breathing disorder affecting more than 15 million Americans. The therapeutic effectiveness of CPAP in providing significant, stable, and long-term neurocognitive or other functional benefits to patients with OSAS has not been systematically investigated. The revised proposed study is a randomized, blinded, sham-controlled, multi-center trial of CPAP therapy. The principal aims of the study are: 1) to assess the long-term effectiveness of CPAP therapy on neurocognitive function, mood, sleepiness, and quality of life by administering tests of these indices to subjects randomly assigned to active or sham CPAP; 2) to identify specific neurocognitive deficits associated with OSAS in a large, heterogeneous subject population; 3) to determine which deficits in neurocognitive function in OSAS subjects are reversible and most sensitive to the effects of CPAP; 4) to develop a composite multivariate outcome measure from the results of this study that can be used to assess the clinical effectiveness of CPAP in improving neurocognitive function, mood, sleepiness, and quality of life; and 5) to use functional magnetic resonance imaging to compare cortical activation

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before and after CPAP therapy, and to assess whether this change is associated with improvement in specific neurocognitive task performance. The primary endpoint of this proposed study is the effect of 6 months of CPAP treatment on neurocognitive function. A total of 1050 subjects (525 per treatment group) will be enrolled from the patient populations at five sites (Stanford; U of Arizona; Harvard; St. Luke's Hospital, MO; St. Mary's Hospital, WA). This study will advance our knowledge of the major, most debilitating, clinically relevant OSAS-associated conditions, and, by scientifically establishing the effectiveness of CPAP therapy, should greatly improve access for the countless victims now denied treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BDNF IN PLASTICITY OF CHEMOAFFERENT PATHWAY Principal Investigator & Institution: Katz, David M.; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2002; Project Start 01-FEB-2002; Project End 31-DEC-2006 Summary: (provided by applicant): The aim of the proposed research is to define the role of Brain-Derived Neurotrophic Factor (BDNF) in activity-dependent plasticity in the developing chemoafferent pathway. Chemoafferent neurons are the link between peripheral chemoreceptors and the brainstem, and thereby play a pivotal role in cardiorespiratory homeostasis. At birth, chemoafferent reflexes are immature, and perturbations in oxygen availability can derange postnatal development of cardiorespiratory responses to acute hypoxia. However, mechanisms that underlie chemoreflex development and plasticity are largely undefined. This proposal is based on our recent discoveries that 1) Chemoafferent neurons in the newborn rat nodosepetrosal ganglion complex (NPG) express high levels of BDNF messenger RNA and protein, 2) BDNF protein is released from NPG neurons in response to patterned electrical stimulation in vitro, and 3) BDNF acutely inhibits glutamatergic AMPA receptors in second-order relay neurons in the nucleus tractus solitarius (nTS), the primary site of chemoafferent projections to the brainstem. Together, these data indicate a new role for BDNF as a modulator of excitatory synaptic transmission between primary chemoafferent neurons and second-order relay neurons in nTS. In view of increasing evidence that BDNF plays a critical role in long-term synaptic plasticity elsewhere in the brain, we hypothesize that BDNF plays a similar role at chemoafferent synapses in nTS. Moreover, based on our preliminary data, we hypothesize that BDNF signaling in nTS is regulated by changes in oxygen availability, and thereby contributes to derangements in chemoreflex function following chronic sustained or intermittent hypoxia. Therefore, the proposed research is designed to further define mechanisms of BDNF expression and release in chemoafferent neurons after birth, including the role of chronic sustained and intermittent hypoxia, in vivo and in vitro. In addition, we will characterize postsynaptic effects of BDNF on developing nTS neurons, including regulation of transmitter receptor expression and dendritic growth. Moreover, we will determine the role of BDNF in functional plasticity in vivo by analyzing development of peripheral chemoreflexes in transgenic mice in which BDNF signaling is disrupted selectively after birth. By defining mechanisms of activity-dependent plasticity in the PG and nTS, the proposed research may shed light on cellular and molecular mechanisms relevant to understanding and improved management of hypoventilation and apnea syndromes in neonates and infants, as well as mechanisms that contribute to altered cardiorespiratory control in adult obstructive sleep apnea and chronic obstructive pulmonary disease. Moreover, it is hoped that elucidating development of this system

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will, in turn, create a model of neurotrophin function applicable to the nervous system as a whole. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CARDIOVASCULAR DISEASE MECHANISMS IN SLEEP APNEA Principal Investigator & Institution: Somers, Virend K.; Professor; Mayo Clinic Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-AUG-2003 Summary: Obstructive sleep apnea is emerging as an important risk factor for hypertension, heart failure, and ischemic heart disease. The mechanisms linking obstructive sleep apnea to cardiac and vascular disease are poorly understood. Utilizing recent developments in neural circulatory control and in vascular biology, we have acquired exciting preliminary data that promise mechanistic insight into the association between sleep apnea and cardiovascular disease. These data suggest that patients with sleep apnea have: 1) increased sympathetic neural traffic, tachycardia, and marked impairment of heart rate and blood pressure variability; 2) impaired endothelial vasodilator function; 3) dramatic overnight increases in endothelin and cytokines, with reductions in both after acute continuous positive airway pressure (CPAP) therapy; and 4) a reduction in blood pressure and sympathetic drive after long-term CPAP therapy. These interesting findings have led us to propose the overall hypothesis that obstructive sleep apnea is associated with neural, vasoactive and inflammatory abnormalities, which may be implicated in cardiovascular dysfunction, and that these abnormalities are attenuated by long-term therapy with CPAP. We will test the following specific hypotheses: 1) That patients with sleep apnea have impaired neural mechanisms regulating circulatory control. 2) That patients with sleep apnea have impaired endothelial function, and increased production of endothelin, cytokines and leukocyte adhesion molecules. 3) That long term effective therapy with CPAP improves cardiovascular function by attenuation of these abnormalities in neural, vasoactive and inflammatory mechanisms. An important and novel strength of these studies is that the integrity of the hypotheses will be tested with careful exclusion of potential confounding variables such as obesity, hypertension, left ventricular dysfunction, exercise capacity and impaired glucose tolerance. This proposal builds on our broad experience in studies of both sleep apnea and neural circulatory control, and should contribute to the understanding and treatment of cardiac and vascular disease in patients with obstructive sleep apnea. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CARDIOVASCULAR RESPONSES TO CHRONIC INTERMITTENT HYPOXIA Principal Investigator & Institution: Mifflin, Steven W.; Professor; Pharmacology; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, Tx 78229 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-AUG-2004 Summary: Chronic intermittent hypoxia (CIH) is a widely used model for the repetitive bouts of hypoxemia that occur during sleep in sleep apnea patients. During such apneic periods, hypoxia activates chemoreceptors that evoke reflex increases in arterial pressure. In humans with sleep apnea and animals exposed to CIH the repetitive periods of hypoxia during sleep result in tonically increased arterial pressure during waking hours, likely the result of elevated levels of sympathetic nerve activity and an enhanced response to acute hypoxia. The goal of the present project is to investigate the

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central pathways and mechanisms that underlie this persistent increase in sympathetic nerve activity. It is hypothesized that CIH leads to alterations in ligand gated excitatory and/or inhibitory amino acid receptors in noradrenergic (A2) neurons in the nucleus of the solitary tract (NTS) so that their discharge is increased compared to before CIH. These neurons transmit this enhanced discharge to sympatho-excitatory neuron in the paraventricular nucleus (PVN) of the hypothalamus. PVN neurons receiving the catecholaminergic input include neurons that release corticotropin releasing factor (CRF) as a transmitter. The CRF releasing PVN neurons mediate, at least in part, the enhanced sympathetic discharge observed following CIH via projections to the RVLM and by stimulating corticosterone release. Both in vivo and in vitro approaches will be used and microinjection, electro-physiological and molecular studies are proposed to characterize the synaptic integration of chemoreceptor inputs and the molecular regulation of the neurotransmitter receptors that mediate these integrative processes. The specific aims are designed to assess: 1) The integration of arterial chemoreceptor inputs within the NTS following CIH; 2) The integration of A2, noradrenergic inputs within the PVN following CIH; and 3) The functional activation of the CRF system within the PVN following CIH. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CARDIOVASCULAR STRESS OF SLEEP APNEA AND HEART FAILURE Principal Investigator & Institution: Schwartz, Alan R.; Associate Professor of Medicine; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-JUL-2006 Summary: (provided by applicant): Sleep apnea is a common disorder associated with an increased risk of cardiovascular disease, and is particularly prevalent in heart failure patients. The cardiovascular risk of sleep apnea is likely to be amplified in the presence of heart failure since each disorder can aggravate the other. This proposal examines the interrelationship between sleep apnea and heart failure, and the mechanisms leading to cardiovascular stress when the two interact. Our proposal is predicated on the notion that sleep apnea increases cardiovascular stress, and further worsens left ventricular function in heart failure patients. Our major hypothesis is that a reciprocal interaction exists between sleep apnea and heart failure, wherein sleep-related disturbances in key mediators lead to acute and chronic increases in cardiovascular stress and worsening left ventricular function. To test this hypothesis, experiments are proposed in humans and murine models of sleep apnea and heart failure. In Specific Aims 1 and 2, heart failure patients will be intensively studied nocturnally to elucidate the mechanisms by which sleep apnea and its associated arousals and hypoxemic episodes increase cardiovascular stress acutely and perpetuate cardiovascular stress chronically. In Specific Aims 3 and 4, studies in novel murine models of chronic intermittent and sleepinduced hypoxia will examine the mechanisms in which sleep apnea and heart failure interact at the cardiac and central nervous system level. This potentially harmful interaction will be explored by assessing responses in: (a) novel mediators of cardiovascular stress (reactive oxygen species, cytokines, leptin, and insulin), (b) an important biomarker of acute and chronic cardiovascular stress (B-type natriuretic peptide, BNP), (c) cardiac tissue, and in (d) cardiac and CNS gene expression. The research plan will elucidate new mechanisms causing excess cardiovascular morbidity and mortality in heart failure, as well as provide new approaches to detect, monitor and treat sleep apnea in heart failure patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CAUSES OF SLEEP-INDUCED BREATHING INSTABILITIES Principal Investigator & Institution: Dempsey, Jerome A.; Professor; Preventive Medicine; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2001; Project Start 01-APR-1999; Project End 31-MAR-2003 Summary: During sleep and with the loss of the "wakefulness" drive to pump and upper airway respiratory muscles, the control of breathing becomes highly dependent upon and vulnerable to reflexive feedback inputs from chemoreceptors and mechanoreceptors. Accordingly, sleep-induced breathing instabilities are common and have a significant prevalence even in the general population. Sleep unmasks a highly sensitive hypocapnic-induced apneic threshold, but we do not know what role this mechanism plays in various types of sleep-disordered breathing, because we do not know its sites of action, its changes in sensitivity in the presence of powerful background influences such as CNS hypoxia, chronic hypocapnia/hypercapnia, changing sleep states, or changing stimuli to breathe which might be specific to sleep. We will use sleeping humans and dogs, the latter with extra corporeal perfusion of isolated carotid chemoreceptors-to quantify the effect of these influences on both the apneic threshold and on the important stabilizing mechanism of short term potentiation of ventilatory output. This dog model with isolation of carotid chemoreceptors will also be used to address the question of central versus peripheral hypoxic effects on periodic breathing in sleep. A second dog model as well as human patients with chronic heart failure will be studied to address the mechanisms of Cheyne-Stokes respiration, with specific emphasis on the effects of the added stimulus to hyperventilation originating from the lungs of the patient in congestive heart failure. Finally, we will use dogs and humans-with and without innervated lungs-to address the role of non-chemical, mechanoreceptor inhibitory feedback effects during sleep on upper airway and pump muscles; a) influences from high frequency low amplitude pressure oscillations in the upper airway; b) the effects of amplitude, timing and duration of normocapnic mechanical ventilation on the resetting of inherent respiratory rhythm and on the "shortterm inhibition" of respiratory motor output following cessation of phasic inhibitory sensory input. These latter studies conduced in sleep are important to testing the sensitivity of respiratory control mechanisms to mechanical feedback-a problem which remains relatively unexplored, especially in the human. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CHEMORECEPTORS AND HYPERTENSION AND SLEEP APNEA Principal Investigator & Institution: Loredo, Jose S.; Medicine; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 92093 Timing: Fiscal Year 2001; Project Start 01-AUG-1999; Project End 31-JUL-2004 Summary: The career development plan for this award will consist of two components: A research project and a didactic program. The research project aims to characterize the function of peripheral chemoreceptors and their relation to the sympathetic nervous system (SNS) and blood pressure (BP) in hypertensive patients with obstructive sleep apnea (OSA). Previous work has suggested that apneic hypertensives have high tonic chemoreceptor activity, and depressed chemoreceptor sensitivity. The project's hypothesis is that high tonic chemoreceptor activity contributes to the development of maintenance of hypertension and high SNS tone in OSA patients. To test this hypothesis it is necessary to study four groups of patients: hypertensives and normotensives , with and without sleep apnea. The specific goals of this randomized double blind cross over study include 1) Characterization of tonic chemoreceptor activity by measuring

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ventilation at room air and during chemoreceptor blockade with 100% O2. 2) Characterization of chemoreceptor sensitivity by measuring ventilation during hypoxia. 3) Characterization of SNS activity at baseline and its response to chemoreceptor blockade or stimulation. 4) Determination of the effect of 7 days nocturnal supplemental O2 on BP, SNS, and chemoreceptor function. If the hypothesis is correct, that high tonic chemoreceptor activity is associated with hypertension and high SNS activity in OSA patients, then treatment with supplemental oxygen may decrease BP and normalize SNS function. A short term implication is that patients with mild to moderate OSA unable to tolerate continuous posit8ive airway pressure, may benefit from nocturnal O2 alone. The didactic program will supplement the clinical research training background of the applicant. The program includes courses in epidemiology, biostatistics, and sleep medicine. Further didactic instruction will include courses and symposia on advanced statistics, clinical trials design and ethical conduct of clinical research. This training will provide the basis of an MPH degree and a solid theoretical background for future conduct of quality clinical research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHOLINERGIC ASPECTS OF THE CAROTID BODY IN SLEEP APNEA Principal Investigator & Institution: O'donnell, Christopher P.; Associate Professor of Medicine; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-AUG-2004 Summary: The prevalence of Obstructive Sleep Apnea (OSA) is increasing dramatically in the U.S. representing a serious health risk. The primary consequence of airway obstruction during sleep is to cause hypoxemia which stimulates the carotid body, leading to increased respiratory drive until arousal from sleep restores upper airway patency. This project proposes to determine the mechanisms by which the carotid body senses and responds to the repetitive intermittent periods of hypoxemia in OSA. Based on the critically important role of acetylcholine as an excitatory neurotransmitter in the carotid body's chemotransduction of hypoxia, it is hypothesized 1) that the repetitive intermittent hypoxia of OSA alters cholinergic transduction pathways in the carotid body, and 2) that the sensitivity of the carotid body is determined genetically. Specific Aim 1 will examine the impact of repetitive intermittent hypoxia during sleep on carotid body function in a novel, murine model of sleep disordered breathing. Specific Aim 2 will investigate the pattern of acetylcholine and other neurotransmitter release from the carotid body, as well as recording carotid sinus nerve activity, in response to repetitive intermittent hypoxia. Specific Aim 3 will use immunohistochemical and patch clamp analyses to determine if neuronal nicotinic acetylcholine receptors (nAChRs) can account for differential hypoxic responsiveness between mouse strains with differential hypoxic responsiveness and determine whether repetitive intermittent hypoxia upregulates expression of subtypes of nAChRs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: COGNITIVE BENEFITS OF TREATING SLEEP APNEA IN DEMENTIA Principal Investigator & Institution: Ancoli-Israel, Sonia A.; Professor; Psychiatry; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 92093 Timing: Fiscal Year 2001; Project Start 01-MAY-1989; Project End 31-JAN-2006

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Summary: (adapted from Investigator's abstract) Studies have shown that there is a strong relationship between sleep disordered breathing (SDB) and dementia and patients with Alzheimer's Disease having a high rate of SDB. This application will examine whether treating SDB with nasal CPAP in patients with AD will result in improvement in cognitive functioning. The specific aims are to assess whether patients with mild AD will tolerate CPAP and be compliant with the treatment; to examine the effect of CPAP treatment on SDB; to examine the effects of CPAP treatment on cognitive functioning in patients with mild AD and SDB; to examine whether improvement is greater after 6 weeks of CPAP treatment than after 3 weeks. Because caregivers are often disturbed by the patient's poor sleep, the effect of treatment on the caregiver will also be evaluated. The secondary aim is to evaluate whether caregivers feel that their own sleep improves as the patient's sleep improves. Patients will be randomized to a CPAP treatment group or sham CPAP group. After 3 weeks, the sham group will also be switched to CPAP. Measures of neuropsychological performance will be obtained at baseline and after 3 and 6 weeks of treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COMPUTATIONAL STUDIES OF THE RESPIRATORY BRAINSTEM Principal Investigator & Institution: Lindsey, Bruce G.; Professor; Physiology and Biophysics; University of South Florida 4202 E Fowler Ave Tampa, Fl 33620 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): Understanding the control of breathing is an important goal in integrative biology and medicine. Sleep disorders in newborns and adults that disrupt breathing have been implicated in the development of pulmonary and systemic hypertension and other disorders and risks. The goal of this collaborative project is to develop a unified model of the brainstem respiratory network and to identify potential sites where abnormalities can disrupt breathing and its control. Detailed biophysical and large-scale simulations will guide associated in vivo and in vitro neurophysiological and pharmacological experiments to test model-based hypotheses on sub-cellular, cellular, network and systems level mechanisms that transform the respiratory network during the transitions between eupnea and hyperventilation apnea, from eupnea to gasping, and during sleep and waking. Experimental feedback will be used to iteratively tune the model. The project has five aims: 1. Develop a comprehensive computational model of the ventrolateral medullary "core" respiratory network and use it as a tool for interactive modeling/experimental studies on the neural control of breathing. 2. Evaluate interactions among the medullary central pattern generator (CPG), the pontine respiratory group, the nuclei of the solitary tract, and the raphe nuclei. 3. Elucidate mechanisms underlying network reconfiguration and the respiratory motor patterns associated with transient changes in chemical drive and gasping. 4. Identify inputs to the pontine-medullary respiratory network that can produce the respiratory motor patterns observed during the sleepwake cycle and that can cause sleep apnea. These inputs or their absence are ultimately responsible for sleep disorders. 5. Test biophysical, cellular, and network mechanisms for a) rate and synchrony "coding" and network stability. This project will bring together researchers from universities in five states. Members of the group have a common interest in the control of breathing, complementary areas of expertise, large and growing experimental databases, and long-standing collegial relationships. The project will be a catalyst for the development and sharing of advanced multi-array recording technologies and computational methods, modeling and simulation tools, and large data sets.

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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CONTROL SLEEP/WAKEFULNESS

OF

AIRWAY

MOTOR

NEURONS

DURING

Principal Investigator & Institution: Siegel, Jerome M.; Professor; Brain Research Institute; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2001; Project Start 01-SEP-1998; Project End 31-AUG-2003 Summary: The loss of upper airway muscle tone in sleep is the precipitating cause of sleep apnea. Sleep apnea affects 3-5% of men over 40 and 1.5-2.5% of post-menopausal women. It causes persistent sleepiness, exacerbates a variety of medical conditions and increases morbidity and mortality. We will study how forebrain sleep induction mechanisms cause the reduction of muscle tone in airway dilators. A variety of complementary techniques will be used in sleep apnea patients to determine which forebrain and brainstem regions are activated and inactivated during airway obstruction. In projects 2 and 3 the pathways from forebrain sleep inducing regions will be traced to the brainstem region activated and inactivated in sleep apnea, focusing on regions controlling upper airway muscle tone. These studies will use anatomical tract tracing techniques, thermal activation of sleep controlling neurons and unit recording in the posterior hypothalamus, periaqueductal gray and medulla of unrestrained animals. In projects 4 and 5 we will determine which amino acid and monoamine transmitters mediate the suppression of muscle tone in airway dilator motoneurons during REM and non-REM sleep. These studies will use in vivo microdialysis, intracellular unit recording and iontophoresis. This program will bring basic science techniques to bear on the important clinical problem of sleep apnea. Pilot studies for this collaborative enterprise have already yield data that will produce a major revision in our understanding of the mechanisms controlling the airway during sleep. The work of this SCOR (Specialized Center of Research) will increase our understanding of sleep apnea. It is also likely to be of importance to other disorders of motor control during sleep. It is also likely to be of importance to other disorders of motor control during sleep, including REM sleep behavior disorder, bruxism, periodic limb movements during sleep and cataplexy. This research will also shed light on the cellular mechanisms controlling REM and non-REM sleep states. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CONTROL OF BREATHING DURING PHYSIOLOGIC CONDITIONS Principal Investigator & Institution: Forster, Hubert V.; Professor; Physiology; Medical College of Wisconsin Po Box26509 Milwaukee, Wi 532264801 Timing: Fiscal Year 2001; Project Start 01-JUN-1986; Project End 31-MAY-2005 Summary: Several theories on the neural control of breathing that were based on data from reduced preparations were not supported by our recent findings in awake and asleep goats on the effects of rostral medullary neuronal dysfunction and/or carotid body denervation (CBD). Some findings mimicked the altered breathing found in obstructive sleep apnea (OSA) and congenital central hypoventilation syndrome (CCHS). The mechanisms that mediated these effects are not established, but one likely mechanism is through intracranial chemoreceptors for years thought to exist only near the ventral medullary surface (including the retrotrapezoid nucleus RTN)). However, findings in reduced preparations of chemoreceptors at widespread brain sites have raised questions related to the location and role of chemoreceptors that affect breathing

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in awake and asleep states and whether brain chemoreceptor sensitivity is altered by CBD. One recently identified site of chemoreception is the medullary raphe nuclei (MRN) whose role in the control of breathing during awake and asleep states remains speculative. Accordingly, to study chemosensitivity and the role of the RTN and MRN in the control of breathing, we will implant microtubules into these nuclei of goats to: a) create a focal acidosis by dialysis of mock cerebrospinal fluid with different PCO2's, or b) induce neuronal dysfunction through injection of glutamate or serotonin receptor antagonists or agonists, or a neurotoxin. Major hypotheses are: 1) focal acidosis (equivalent to that breathing 7 percent inspired CO2, delta brain pH approximately -.05) in the RTN will increase breathing in awake, but not asleep states, while acidosis in the MRN will increase breathing in asleep, but not awake states, 2) at RTN sites where focal acidosis increases breathing, neuronal dysfunction will attenuate whole body CO2 sensitivity, but not alter rest and exercise breathing, 3) neuronal dysfunction in the MRN will attenuate CO2 sensitivity and rest and exercise breathing, 4) during the first 10 days after CBD, the effect of RTN and MRN focal acidosis will be attenuated but 15 plus days after CBD, the effect of focal acidosis will be accentuated. and 5) at most RTN and MRN sites, the acute effects of neurotoxic lesions will be hypoventilation (rest and exercise) and attenuated CO2 sensitivity; the acute effects of these lesions will be greater in CBD than in intact goats, but recovery after lesioning will be greater in intact than in CBD goats. Our unique studies are important because hypotheses generated largely from reduced preparations will be tested in awake and asleep states to enhance the understanding of medullary chemoreceptor contribution to the control of breathing and how abnormalities in this contribution may underlie diseases such as OSA, CCHS, and the Sudden Infant Death Syndrome. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CONTROL OF BREATHING IN RECOVERY FROM APNEA Principal Investigator & Institution: Thach, Bradley T.; Professor; Pediatrics; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2001; Project Start 30-SEP-1977; Project End 31-MAY-2004 Summary: The Sudden Infant Death Syndrome (SIDS) remains a leading cause of infant deaths inspite of recent highly successful public health interventions designed to reduce SIDS risks (The U.S. "Back to Sleep" campaign, "BTS"). We propose to study several physiologic and neuro-developmental mechanisms potentially involved in the etiology of SIDS, as well as, pertinent environmental factors. The research will focus on three areas. In the first of these, we plan to study the physiology of recovery from severe hypoxia by gasping (autoresuscitation, AR). These studies will determine if the previously documented developmentally acquired defect in AR, originally described in SWR mice, is present in other inbred strains and species and, furthermore, if underlying mechanisms causing AR failure are similar to those in SWR mice. Additionally, the effects of increased environmental temperature on AR will be evaluated. Also, Home apnea monitor recordings of infants dying suddenly and unexpectedly while being monitored will be studied to determine if there is evidence of attempted AR and if so, potential reasons for its failure. The second part of our studies will be directed to prospectively obtaining data on the case history, death scene and postmortem examination of infant's dying with the diagnoses of SIDS, accidental suffocation and "cause of death undetermined" in the St. Louis metropolitan area. The aim is to determine how many of these deaths are preventable by public acceptance of current "BTS" guidelines and how many might be prevented by future additions or changes in the recommendations to child caretakers. In connection with this study, we will perform

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special death scene investigations in certain SIDS and accidental suffocation deaths combined with laboratory death scene reconstruction studies in order to determine if additional simple guidelines for parents and child equipment manufactures can be formulated in order to prevent infant deaths. Finally, we will study development of the infant's ability to avoid potentially suffocating environments during sleep, and determine the potential role of the infant's past experience on this development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CONTROL-RESPIRATORY MODULATION OF SYMPATHETIC ACTIVITY Principal Investigator & Institution: Dick, Thomas E.; Medicine; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2001; Project Start 01-SEP-2000; Project End 31-JUL-2004 Summary: (Applicant's abstract): Sleep apnea syndrome is prevalent (3-5 percent of the adult population) and associated with significant morbidity including hypertension. The increased blood pressure appears to result from an up-regulation of basal sympathetic nerve activity (SNA). Treatment reverses this up-regulation. We theorize that the upregulation of SNA results from both short- and long-term sequelae of episodic hypoxemia associated with sleep apnea. The respiratory and cardiovascular systems are coordinated in the maintenance of homeostasis. Respiratory modulation of SNA is an aspect of this coordination. Not only is SNA modulated with the respiratory cycle but also this modulation increases during and following brief periods of hypoxemia. The neural substrate for this coordination is undefined. Recent studies have focused on neuronal interaction between medullary respiratory-modulated and pre-motor sympathetic neurons of the rostral ventrolateral medulla (RVLM). However, neurons in the dorsolateral (dl) pontine Kolliker-Fuse (KF) nucleus are the only brainstem neurons other than the those in the NTS that project to the RVLM and that are activated by hypoxia. We hypothesize that a direct pontomedullary interaction between respiratorymodulated neurons of the KF nucleus and neurons in RVLM contributes to the respiratory modulation of sympathetic activity and that this interaction underlies the enhanced respiratory modulation of sympathetic activity during and following hypoxia. To test this hypothesis, we propose a series of neurophysiologic experiments addressing the following specific aims: 1) to determine if inhibition of dl pontine activity blocks the transient and sustained increases in respiratory modulation of SNA during and following hypoxia, 2) to determine if activation of dl pons enhances respiratory modulation of SNA, and 3) to determine if respiratory-modulated KF neurons project to and excite RVLM neurons and if these KF neurons are activated during and after hypoxia. We will investigate the neural substrate controlling respiration and blood pressure, the transient and sustained consequences of brief hypoxemia on this control, and the modulation of this control by morbidity, i.e., the development of hypertension. We propose experiments in normo- and hypertensive rats as well as in cats to evaluate the dl pontine influence on SNA, the changes in this influence with transient hypoxemia and hypertension. These proposed studies examine the mechanism of up-regulation of sympathetic nerve activity that is associated with sleep apnea. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CYCLICAL HYPOXIA--SUSCEPTIBILITY TO NEURONAL INJURY Principal Investigator & Institution: Haddad, Gabriel G.; Pediatrics; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047

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Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-AUG-2002 Summary: In considering how neurons and glia in the central nervous system respond, adapt or get injured when exposed to short and long term hypoxia using cellular and molecular techniques, it has now become clear that the responses to hypoxia and the mechanisms that underlie these responses are dependent on a number of factors, such as severity of hypoxia, history of previous hypoxic exposure, and ontogeny. One of the important consequences of obstructive sleep apnea/hypoventilation syndrome (OSHA) in both children and adults is a cyclical hypoxia with a major O2 desaturations that can occur with every cycle. This cyclical hypoxia generally occurs throughout the night and can repeat itself tens to hundreds of times. The effects of this cyclical hypoxia on behavior and neural function are ill defined. Although there has been a substantial amount of work to delineate the molecular mechanisms of O2 sensing, there are still many important questions that are unanswered. Because cortical neurons have been shown to be vulnerable to hypoxic exposure, the work will focus on the neocortex. Since 1) repetitive hypoxia in OSAH can be severe and can occur over prolonged periods of months and years and 2) the impact of cyclical hypoxia may depend on the level of CNS maturation, the investigators have formulated the following 3 specific hypothesis: 1) invivo cyclical hypoxia renders neurons more susceptible to injury, as evidenced by poor ionic homeostasis and mitochondrial dysfunction, especially when stressed subsequently with hypoxia: 2) in-vivo cyclical hypoxia alters gene expression and renders neurons more susceptible to programmed cell death, and 3) in vivo- cyclical hypoxia has a more profound impact on the inherent electrophysiologic properties of neurons, their metabolism, and their susceptibility to injury and cell death when exposure occurs in early life, as compared to that in the mature rodent. This work may shed light on mechanisms of a variety of diseases, including OSAH, apnea of infancy, postnatal cardiorespiratory diseases that reduce O2 delivery, myocardial infarcts, and cerebro-vascular accidents and stroke. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DEPRESSION, SLEEP DISORDERS AND CORONARY HEART DISEASE Principal Investigator & Institution: Carney, Robert M.; Professor of Medical Psychology; Psychiatry; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-JUL-2003 Summary: Description (adapted from the investigator's abstract): Clinical depression is a risk factor for mortality and morbidity after acute myocardial infarction (MI), yet little is known about the underlying mechanisms that account for this. The purpose of this study is to examine a potential mechanism, cardiovascular response to disordered sleep. Three months after an MI, 75 patients who meet the DSM-IV criteria for major depression will be selected and matched for gender, age, BMI to patients without depression. Polysomnography will be performed to determine the frequency and severity of cardiac responses to sleep disordered breathing and sleep architecture measures. The following hypotheses will be tested: 1) patients with depression have greater cardiac response to episodes of sleep apnea than non-depressed patients; 2) patients with depression without sleep disordered breathing have shorter REM latency, increased REM density, reduced slow wave sleep and worse sleep efficiency; 3) increased cardiac response to sleep disordered breathing, a shorter REM latency, increased REM density, decreased slow wave sleep are associated with electro cardiographic abnormalities predictive of cardiac events in post MI patients.

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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DEVELOPMENTAL REGULATION OF HYPERCAPNIC RESPONSES Principal Investigator & Institution: Martin, Richard J.; Professor; Pediatrics; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2001; Project Start 01-APR-1999; Project End 31-MAR-2003 Summary: Apnea of prematurity is a major clinical problem whose pathophysiology is poorly understood. In preterm infants, especially those with apnea, ventilatory responses to hypercapnia are impaired: preliminary data reveal that hypercapnia causes prolongation of expiratory duration, similar to that observed during hypoxic exposure in early postnatal life. Hypercapnia induced prolongation of expiration is reversed by blockade of GABAA receptors in our neonatal animal models, while hypoxia induced frequency decrease is attenuated alpha2 by adrenergic receptor antagonists applied to the brainstem. We have demonstrated that catecholamine containing cells innervate bulbospinal neurons in newborn rat brainstem and that a subpopulation of bulbospinal inspiratory neurons express GABAA receptors. This proposal tests the hypothesis that hypercapnia modulates respiratory timing and the balance of inspiratory and expiratory muscle behavior during early postnatal development. We further hypothesize that C02 induced activation of central inhibitory systems such as GABAergic and alpha2 adrenergic pathways is responsible for maturational changes in these responses. We will administer intracisternal GABAA and alpha2 adrenergic blockers to characterize the role of neuroinhibitory pathways in C02 induced expiratory prolongation in maturing rat pups. We will utilize newborn piglets to characterize the role Of C02 induced chest wall and laryngeal muscle responses in modulating laryngeal resistance during changes in respiratory timing. Microinjection of GABAA and alpha2 adrenergic blockers at sites where brainstem bulbospinal neurons are identified will allow us to characterize the role of these neuroinhibitory pathways in mediating respiratory timing in piglets. Transneural labeling techniques will be combined with immunohistochemistry to characterize the connectivity of neurons in the medulla of maturing rat pups. We will describe expression and agonist affinity of GABAA and alpha2 adrenergic receptors on brainstem inspiratory bulbospinal neurons to test the hypothesis that receptor overexpression or increased agonist affinity contributes to the prolongation of expiration induced by hypercapnia during early life. Characterization of central neurochemical pathways that contribute to impaired hypercapnic ventilatory responses may advance our understanding of the pathogenesis of neonatal apnea and contribute to novel pharmacologic interventions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DIASTOLIC DYSFUNCTION & ATRIAL FIBRILLATION IN ELDERLY Principal Investigator & Institution: Tsang, Teresa S.; Mayo Clinic Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): Nonvalvular atrial fibrillation (AF) is an age-related public health problem associated with marked morbidity and mortality. We propose to prospectively examine the structural, hemodynamic, and neurohormonal/ inflammatory factors associated with first AF and investigate whether sleep apnea independently predicts AF. In Aim 1, we will confirm that diastolic function and left atrial (LA) volume are predictive of AF, incremental to clinical and other

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echocardiographic variables. We hypothesize that diastolic dysfunction and increased LA volume independently predict nonvalvular AF. In Aim 2, the distribution and correlates of changes in diastolic function and LA volume will be described, and we will determine whether serial measurements of these parameters provide incremental information on risk of AF. In Aim 3, we plan to explore how neurohormonal activation, specifically atrial natriuretic peptide (ANP) release, and the inflammatory marker, Creactive protein (CRP), are associated with LA size, diastolic function, and AF development. We hypothesize that there is an independent role for ANP, but not for CRP, in the prediction of AF, after clinical and echocardiographic parameters have been considered. In Aim 4, we will assess relationships between arterial stiffness, diastolic function and LA volume, and determine whether arterial stiffness independently predicts AF. In Aim 5, we will evaluate sleep apnea as an independent predictor of AF development, after accounting for other clinical and echocardiographic risk factors. We plan to recruit 800 adults at significant risk for nonvalvular AF on the basis of age > 65 years and the presence of two or more known AF risk factors (hypertension, diabetes, history of coronary artery disease, and history of congestive heart failure). Prior history of AF, embolic stroke, organic valvular disease and congenital heart disease are the major exclusion criteria. All participants must be able to provide informed consent. Echocardiography, electrocardiogram (ECG), ANP, CRP, noninvasive arterial stiffness assessments (pulse wave velocity and augmentation index) will be obtained at baseline and annually thereafter. The Berlin Sleep Questionnaire to assess risk of sleep apnea will be completed by all participants at baseline and annually. A subgroup of 200 participants will undergo sleep studies, using a portable recording system, for detection of sleep apnea. Ascertainment of AF involves regular ECG surveillance, and patient report of AF with ECG confirmation. Identification of the cascade of factors contributing to AF development will have important implications in primary prevention of this major public health problem. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DIFFERENTIAL VULNERABILITY TO MORBIDITIES OF SLEEP APNEA Principal Investigator & Institution: Veasey, Sigrid C.; Professor; Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-JUL-2004 Summary: (Adapted from the applicant's abstract) Obstructive sleep apnea (OSA) affects over 2% of the adult population in the United states and is associated with significant neurobehavioral and cardiovascular morbidities. The morbidities of OSA relate at least in part to sleep fragmentation and intermittent hypoxia, both consequences of sleep- related collapse of the upper airway. In humans with OSA, there is significant variance in the manifestation of both the neurobehavioral and cardiovascular consequences. This variance in morbidity is only partially explained by the severity of disease. These investigators believe that vulnerability tot he morbidities of OSA is, in part, genetically-determined. For this proposal, they will focus on the substantial neurobehavioral consequences of sleep apnea. To begin to determine the genetic mechanisms contributing to the differential vulnerabilities, they will look separately at sleep fragmentation and chronic intermittent hypoxia (CIH) responses in inbred strains of mice. They will first expand the phenotypical response to sleep disruption to include, not only electroencephalographic changes, but also to characterize the neurobehavioral responses: sleepiness, changes in motor activity, learning, short and long term memory, vigilance and recovery for each of these parameters following

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

Project Title: EFFECT OF SLEEP DEPRIVATION ON INFLAMMATORY MARKERS Principal Investigator & Institution: Wright, Kenneth P.; Associate Neuroscientist; Integrative Physiology; University of Colorado at Boulder Boulder, Co 80309 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2005 Summary: (provided by applicant): Heart disease, vascular disease and respiratory sleep disturbance are common and complex disorders with interactions among the cardiovascular, immune, neuroendocrine, sleep and circadian systems. Because inflammation in response to acute and chronic stress responsible for tissue damage associated with disease, recent efforts to understand mechanisms underlying these disorders have lead to studies that investigated inflammatory markers. These research efforts have revealed that high plasma levels of several novel inflammatory markers-cell adhesion molecules and pro-inflammatory cytokines-predict cardiovascular morbidity and mortality. High plasma levels of these markers are also reported to be associated with the severity of sleep apnea. A variety of stressors have been reported to initiate the inflammatory response, however, whether the stress of sleep deprivation also produces higher levels of these novel inflammatory markers is unknown. The current grant application takes an integrative physiological approach to understanding health consequences of sleep deprivation by forming new collaborations between experts in vascular physiology, neuronimmunophysiology, neuroendocrinology and sleep and circadian physiology. We are requesting funds to analyze existing biological specimens that were collected under controlled laboratory conditions from healthy women and men who underwent baseline sleep and wakefulness recording and 40 hours of total sleep deprivation. We propose to test the following specific hypothesis: 0 that acute total sleep deprivation will increase circulating levels of proinflammatory cell adhesion molecules; and ii) that acute total sleep deprivation will increase circulating levels of pro-inflammatory cytokines. We also propose to measure stress hormones to determine the relationship between changes in inflammatory cell adhesion molecules, cytokines and stress hormones during sleep deprivation and during baseline sleep. Because sleep loss is an independent risk factor for heart disease and chronic sleep loss is a consequence of sleep apnea, the results of the proposed study could have important implications for understanding the molecular mechanisms underlying these disorders and their association with sleep loss. This work could also have a significant impact on our understanding of the health consequences of sleep loss, which would have implications for public health and safety. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EFFECTS OF SLEEP APNEA ON METABOLIC FUNCTION Principal Investigator & Institution: Punjabi, Naresh M.; Associae Professor; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-JUL-2007

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Summary: (provided by applicant): Sleep apnea is a chronic condition associated with an increased risk of hypertension and cardiovascular disease. Recent data suggest that sleep apnea is also associated with metabolic dysfunction that is characterized by glucose intolerance and insulin resistance. Although several studies indicate that the association between sleep apnea and metabolic dysfunction is independent of confounders including obesity, it remains to be determined whether the association is causal. Moreover, whether intermittent hypoxemia and/or sleep fragmentation are in the putative causal pathway is unknown. The major objective of our proposal is to determine whether sleep apnea produces metabolic dysfunction and delineate the underlying mechanisms. Our primary hypothesis is that intermittent hypoxemia and recurrent arousals from sleep lead to acute and chronic changes in metabolic function. In Specific Aim 1, we will examine whether nighttime and daytime profiles of metabolic function differ between patients with sleep apnea and control subjects matched on age, race, gender, and obesity. We hypothesize that, compared to control subjects, patients with sleep apnea will demonstrate: a) marked abnormalities in nighttime profiles of glucose, insulin, and insulin secretion rate; b) impairment in daytime glucose tolerance, insulin sensitivity, and glucose effectiveness; and c) an increase in sympathetic activity and serum levels of leptin, cortisol, IL-6, and TNF-ct that are independently correlated with the severity of intermittent hypoxemia and frequency of arousals. In Specific Aim 2, we will examine whether experimental sleep fragmentation and sleep apnea (sleep fragmentation with intermittent hypoxemia) alter metabolic dysfunction in normal subjects. We hypothesize that: a) sleep fragmentation in normal individuals will alter nighttime profiles of glucose, insulin, and insulin secretion rate and worsen daytime measures of glucose tolerance, insulin resistance, and glucose effectiveness; b) intermittent hypoxemia in association with sleep fragmentation will potentiate the adverse effects of sleep fragmentation alone; and c) experimental sleep fragmentation and sleep apnea will increase sympathetic activity and serum levels of cortisol, leptin, TNF-alpha and IL-6 in association with impaired glucose homeostasis. Novel experimental paradigms have been developed to determine the independent roles of sleep fragmentation and sleep apnea on metabolic function. Given the epidemic of obesity and diabetes, understanding the role of sleep apnea as a risk factor for metabolic dysfunction has public health significance in terms of prevention and treatment of diabetes, hypertension, and cardiovascular disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EFFECTS OF TREATING OBSTRUCTIVE SLEEP APNEA IN EPILEPSY Principal Investigator & Institution: Malow, Beth A.; Associate Professor; Neurology; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 31-JUL-2003 Summary: (provided by applicant): Epilepsy affects approximately 2.5 million Americans, resulting in substantial disability. Because up to 30% of patients with epilepsy continue to have seizures despite appropriate treatment with antiepileptic medications, additional interventions to improve seizure control are needed. One approach to improving seizure control is to treat coexisting sleep disorders, such as obstructive sleep apnea. Obstructive sleep apnea (OSA) may exacerbate seizures via sleep fragmentation, sleep deprivation, or other pathophysiological processes that have not yet been determined. The investigators recently documented that OSA is common in epilepsy patients with seizures refractory to medical treatment. In addition, preliminary data in the form of retrospective case series by the investigators and others have

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suggested that treatment of OSA may improve seizure control. However, no prospective studies have been done to verify these findings. Proof that treating OSA is effective in reducing seizure frequency will require a multicenter Randomized Clinical Trial (RCT). This large RCT will test the hypothesis that treatment of OSA in patients with epilepsy refractory to medical treatment will reduce seizure frequency. In addition, the RCT will assess the impact of treating OSA on health-related quality of life and on daytime sleepiness, common concerns in epilepsy patients that are often attributable to antiepileptic medications or to frequent seizures rather than to a coexisting sleep disorder. The proposed aims of the Pilot Clinical Trial (PCT) are to determine critical information for the design of the RCT to allow for the testing of the above hypotheses in the RCT. In the PCT subjects 18 years and older with 4 or more seizures per month who meet survey criteria for OSA and other study criteria will be recruited at 3 different sites from epilepsy patients seen in clinical settings. A total of 60 subjects will be observed longitudinally through PSG confirmation and treatment of OSA and randomized to either therapeutic continuous positive airway pressure (CPAP) or sub-therapeutic (placebo or sham) CPAP in order to determine tolerability. Rates of adherence to therapeutic and sham CPAP and dropout rates due to antiepileptic drug changes during the treatment phase will be estimated. Specifically, the proposed PCT will: 1. Evaluate screening ranges on the Sleep Apnea scale of the Sleep Disorders Questionnaire (DA/SDQ), a survey instrument that is used to determine whether subjects are eligible for inclusion into the RCT. 2. Determine the necessity of performing two nights of PSG in patients with epilepsy. A second night of study increases the cost and may decrease recruitment in the RCT, but may be important to include given the night-to-night variability in the PSG and the potential for seizure occurrence during recordings. The working hypothesis is that one night of PSG will be sufficient for the RCT. 3. Determine rates of adherence to therapeutic and sham CPAP, dropout rates due to antiepileptic drug changes, and response rates will provide valuable data for planning the RCT. 4. Develop quality control measures to ensure accurate and consistent data collection among sites in the RCT, including aspects related to remote data entry and standardization of performance and interpretation of PSG studies across sites. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EPISODIC INFLAMMATION

HYPOXIA

AND

ACUTE

CEREBROVASCULAR

Principal Investigator & Institution: Gidday, Jeffrey M.; Assistant Professor; Neurological Surgery; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-AUG-2004 Summary: A significant percentage of newborns become intermittently hypoxic secondary to complications during labor and delivery, apnea of prematurity, and respiratory distress syndrome. Although brain injury is suspected in some cases, the potential mechanisms by which episodic hypoxia might cause cerebral dysfunction and neurodevelopmental handicaps are, at present, purely speculative. Thus, no prophylactic treatments are available. In order to develop rational therapeutics to reduce brain injury from intermittent hypoxia, a better understanding of the effects of this stress on the newborn brain needs to be realized by studies in appropriate preclinical models. The general hypothesis is that intermittent hypoxia stimulates the production of interleukin-1B, superoxide radical, and adenosine, and concomitantly inhibits the production of nitric oxide. It is hypothesized that these changes, singly and in combination, activate edothelium, upregulate adhesion molecule expression, and

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promote an inflammatory response that jeopardizes microcirculatory flow, vascular reactivity, and blood-brain barrier integrity. The specific aims are: 1) To examine the role of the cytokine interleukin-1B (IL-1B) in mediating leukocyte endothelial adherence secondary to its induction of E-selectin and intercellular adhesion molecule-1 (ICAM); 2) To investigate the participation of superoxide radical in mediating leukocyte-endothelial adherence in response to intermittent hypoxia; 3) To examine how nitric oxide (NO) affects leukocyte-endothelial interactions and their consequences in the setting of intermittent hypoxia; and 4) To elucidate the involvement of adenosine and its receptors in the inflammatory response to intermittent hypoxia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EVALUATION OF DIAGNOSTIC TESTS FOR PEDIATRIC SLEEP APNEA Principal Investigator & Institution: Rosen, Carol L.; Associate Professor; Pediatrics; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2001; Project Start 01-AUG-2000; Project End 31-JUL-2005 Summary: The candidate is an experienced academic clinician, trained in pediatric pulmonology and sleep medicine, who plans to re-train in clinical epidemiology. This award is expected to help transition the candidate's focus from physiological testing to clinical epidemiology. The candidate's career goals are to develop an independent research career concentrating on the identification, diagnosis, treatment, and outcomes assessment of obstructive sleep apnea (OSA) in children. The specific objective of the research proposal is the rigorous systematic assessment (reliability, accuracy, and cost effectiveness) of a diagnostic strategy for OSA in children that relies on clinical predictors and simplified home (unattended) monitoring. The candidate proposes a five-year training program with an experienced team of faculty mentors from strong research departments. This plan describes activities (advanced degree coursework, independent study, patient based clinical research) focused on developing skills in clinical epidemiology with immediate applications to the diagnosis of sleep disordered breathing in children. Specific activities in the plan include research training in statistical methods, experience with data analysis in large databases, supervised experience in preparation of grant proposals for individual research support, and training in the responsible conduct of research. The proposed research addresses important knowledge gaps about diagnostic testing for OSA in children and provides important new data for rational and cost-effective application of technology to an under-recognized health condition of children. Furthermore, clarification of the role of diagnostic testing and outcome assessment in pediatric OSA will be crucial for future randomized controlled trials of treatment efficacy; mechanistic studies, and population based studies of pediatric sleep disorder breathing. Finally, the proposal will provide a key training opportunity to foster the candidate's career development as a clinical epidemiologist with a commitment to patient based research in pediatric sleep medicine and pulmonology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: FAMILIAL AGGREGATION AND NATURAL HISTORY OF SLEEP APNEA Principal Investigator & Institution: Redline, Susan S.; Professor of Pediatrics, Medicine & Epid; Medicine; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106

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Timing: Fiscal Year 2001; Project Start 01-AUG-1990; Project End 31-MAR-2006 Summary: In this genetic-epidemiological study of Obstructive Sleep Apnea (OSA), we propose further investigation of the genetic and etiologic bases for OSA and OSAassociated co-morbidities in a unique, racially diverse family cohort (n= 2200) who have previously undergone overnight sleep studies. Cohort members from structurally informative families for OSA (n=700), most of whom will have had a genome scan performed prior to the study's inception, will undergo additional physiological and biochemical measurements and longitudinal follow-up to derive detailed phenotypic characterization of OSA and related cardiovascular disease (CVD) risk factors and subclinical disease. Newly available technology will be used to quantify specific and sensitive indices of obstructive breathing parameters and sleep fragmentation. These will provide more precise estimates of the OSA phenotype. Subjects also will undergo a biochemical profile and evaluations of vascular function, including assessment of novel CVD risk factors that may be related to OSA based on: i. common genes (e.g., that influence fat distribution); and/or ii. their role as indices of OSA disease severity (e.g., reflecting hypoxic or adrenergic tissue responses). Studies include: In-laboratory determination of sleep-related hypoxemia, arousal, airflow limitation and respiratory effort; b. In-laboratory assessment of biochemical markers, anthropometry, and physiological functions (many measured both in the evening and morning surrounding the sleep study); c. In-home re-assessment of the apnea hypopnea index (AHI), using comparable technology to what was used in the first 10 years of the study. Rigorous analyses, using a variance components-segregation analysis framework, will be used to: i. derive new phenotypes for OSA with estimates of heritability; ii. Assess genetic linkages for these phenotypes; iii. Determine metabolic and vascular responses to OSArelated nocturnal stresses; iv. Model longitudinal changes in the AHI. We will dissect the sharing or non-sharing of the genetic and non-genetic determinants of phenotypes potentially on a causal pathway leading to OSA. Additional longitudinal follow-up of this cohort will identify determinants of OSA progression, the co-variation of OSA with other risk factors, and its natural history. These studies will provide new data that will address the genetics and pathophysiology of OSA and associated traits. Such data are needed to address critical questions regarding the treatment and prevention of a disorder with a huge public health impact related to its high prevalence and associated co-morbidity (CVD, hypertension, sleepiness, impaired quality of life, accidents). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FUNCTIONAL NEAR INFRARED IMAGING SYSTEM Principal Investigator & Institution: Barbieri, Beniamino F.; President; Iss, Inc. 1602 Newton Dr Champaign, Il 61822 Timing: Fiscal Year 2001; Project Start 01-SEP-1999; Project End 31-JUL-2003 Summary: (Provided by Applicant): ISS will develop a novel instrument for the noninvasive imaging of functional activation of the brain. The system will consist of novel hardware and software. The hardware will include 32 laser diode emitters, and 8 photomultiplier tube detectors. Novel features of the hardware will include a customized frequency synthesizer and a customized data acquisition card, both of which will significantly improve imaging performance over current equipment. The software will include real time video maps of multiple tissue properties (hemoglobin oxygen saturation, hemoglobin concentration, and tissue optical parameters). These maps will be generated from a variety of methods including calibrated frequency domain multiple distance (C-FDMD) method, absolute frequency domain multiple distance method, continuous wave differential path length method, and crossed source-

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detector (CSD) path method. This multiplicity of methods will allow maps which benefit from the special characteristics of each method, from the high quantitation of C-FDMD method to the high localization of the CSD method. The system will be tested on phantoms, and in human subjects in conjunction with functional Magnetic Resonance Imaging (fMRI). Upon completion of its design and test, the system will be the world's only commercially available research system for near infrared tissue hemoglobin dynamics imaging. PROPOSED COMMERCIAL APPLICATION: 1. Optical imaging of brain activation and localization of stimulated brain cellular aggregates; 2. Cognitive neuroscience; 3. Brain oxygenation monitoring during cardiac bypass surgery; 4. Sleepapnea studies; 5. Attention deficit disorder investigations Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETICS AND INTERMITTENT MYOCARDIAL HYPOXIA Principal Investigator & Institution: Baker, John E.; Professor; Surgery; Medical College of Wisconsin Po Box26509 Milwaukee, Wi 532264801 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-AUG-2004 Summary: The overall objective is to localize the gene(s) responsible for susceptibility to myocardial ischemia caused by intermittent hypoxia and characterize the physiology in a novel model system. Patients with obstructive sleep apnea have an increased cardiovascular morbidity and mortality. Diseases such as hypertension, hyperlipidemia and diabetes mellitus have an underlying genetic basis and represent risk factors for ischemic heart disease. However, the genetic components(s) underlying the impact of intermittent hypoxia on susceptibility to myocardial ischemia are unknown. It is hypothesized that genetic factors are responsible for increased susceptibility to myocardial ischemia caused by intermittent hypoxia in Dahl S rats compared with Brown Norway rats. This hypothesis will be tested by crossing the Brown Norway with Dahl S rat. The isolated heart model and coronary vessels will be used to facilitate discrete, well-controlled investigations of susceptibility to ischemia with and without prior intermittent hypoxia. A total genome scan will be performed to map quantitative trait loci (QTLs) involved in adaption to intermittent hypoxia and susceptibility to myocardial ischemia. Phenotypic difference between parents and the congenic derivatives resulting form ischemia and reperfusion will be characterized. The specific aims are to: 1) Determine the phenotypic differences of isolated hearts and coronary vessels from the parental strains by studying the responses to: ischemia alone and adaptation to intermittent hypoxia prior to ischemia; 2) Map the gene(s) responsible for adaption in intermittent hypoxia and susceptibility to myocardial ischemia using a total genome scan approach; 3) Develop congenic strains in response to: ischemia alone and adaptation to intermittent hypoxia prior to ischemia; and 4) Use microarray technology to study the expression of genes within the heart adapted to intermittent hypoxia. This project may provide detailed information regarding the genetic basis for adaption to intermittent hypoxia and susceptibility to myocardial ischemia in a genetic model system, which may prove useful for detailed physiological, biochemical and pharmacological assessment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HUMAN FACTORS TO DESIGN SAFE PEDIATRIC SEDATION SYSTEMS Principal Investigator & Institution: Blike, George T.; Anesthesiology; Dartmouth College 11 Rope Ferry Rd. #6210 Hanover, Nh 03755

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Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2004 Summary: (provided by applicant)Goal: Test a Human Factors paradigm to improve efficacy and safety in medical care domains that are accident-prone. The test domain will be pediatric procedural sedation--the treatment of procedure related pain and stress with medication in children. Specific Aims: 1) identify pediatric procedural sedation care system hazards; 2) model modes of failure in the practice of pediatric procedural sedation; 3) innovate error prevention, error recovery and error tolerance strategies for pediatric sedation care systems. Research Design: 1) Simulate two sedation associated events that carry the potential for serious injury or death. Scenarios will be reproducible using a pediatric simulator (Ped-sim TM, Medical Education Technologies, Inc.). Airway obstruction and central apnea are the two sedation events that will be embedded into typical sedation contexts. 2) Study the performance of four Anesthesiology) managing one scenario without an event, one scenario with airway obstruction and one scenario with central apnea. Simulated cases will be assigned using standard scheduling systems and care will be videotaped. 3) Video analysis to identify hazards and vulnerabilities associated with pediatric sedation. Video and verbal data will be used to perform a work analysis in order to define the operators, environment, technology, and patient demands that characterize pediatric sedation when managing sedation associated respiratory events. Qualitative methods (protocol analysis, process tracing and hazards analysis) and semi-quantitative methods (that measure operative conditions, response times, accuracy rates, simulator hypoxia of PaO2 < 27 in seconds) of analysis will be employed. 4) Engineering safety into sedation care systems. The goal is to iteratively design novel "best practices for sedation care that not only prevent error, but also create error tolerance and error recovery at the system level Hazards identified in steps 1-3 will be the focal point of design efforts. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HYPOTHALAMIC REGULATION OF RESPIRATION DURING SLEEP Principal Investigator & Institution: Mcginty, Dennis J.; Adjunct Professor; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 31-AUG-2002 Summary: Much evidence supports a hypothesis that hypothalamic preoptic area (POA) temperature-sensitive neurons play a critical role in the regulation of NREM sleep, as a component of overall metabolic regulation. The activation of POA warm sensitive neurons is necessary and sufficient for initiation of NREM sleep. The hypnogenic output from the POA is hypothesized to be a descending gamma-aminobutyric acid (GABA)ergic pathway which inhibits arousal-promoting systems in the posterior hypothalamus (PH) and brainstem. In PH, a GABA-regulated system facilitates respiratory motor and autonomic responses. We hypothesize that PH respiratory mechanisms are coupled to PH arousal generating mechanisms, and that arousal induced respiratory facilitation originating in the PH is a critical component of the wakefulness-drive to-breathing. We propose a model in which this drive is actively inhibited during sleep, that this inhibition originates in the POA, and is mediated by GABAergic inhibitory projections from the POA to the PH. The proposed studies will examine hypothesis central to this model. Activation of POA warm-sensitive neurons will 1) suppress diaphragmatic and upper airway dilator activity during sleep and 2) suppress discharge of PH neurons in chronic animals, via a GABAergic process. 3) POA warming will reduce respiratory coupling of medullary reticular neurons. POA cooling will have opposite effects. Obstructive sleep apnea are characterize by sleep onsetinduced airway dilator and respiratory pump muscle deactivation. These events are

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thought to be consequences of the loss of the wakefulness-drive-to-breathing. In addition, many patients exhibit reduced arousal responses and reduced compensation for airway resistance, Thus, we hypothesize that arousal dysregulation is part of the disease. We hypothesize that excessive energy conservation drive, originating in the POA, induces sleepiness and respiratory motor deactivation at sleep onset. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HYPOXIA INDUCIBLE VEGF PRODUCTION IN SLEEP APNEA Principal Investigator & Institution: Levy, Andrew P.; Technion-Israel Institute of Technology Technion City Haifa, Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-AUG-2004 Summary: Angiogenesis is the physiological adaptive response of a tissue to hypoxia. The coronary collateral circulation of the heart represents such an adaptive response and is an important determinant in the extent of tissue damage following myocardial infarction. Autopsy studies have shown that only 50 percent of patients with coronary artery stenosis develop collaterals. A fundamental challenge in understanding the angiogenic response to ischemia in the clinical setting is to elucidate the basis for interindividual differences in the degree of collateral blood vessel formation. Recent evidence demonstrates the importance of differences between patients in the hypoxic regulation of the angiogenic growth factor, vascular endothelial growth factor (VEGF) in determining the extent of collateral blood vessel formation. Specifically, individuals who upregulate VEGF to a greater degree with hypoxia have more collateral blood vessels. The investigators intend to investigate the mechanism for this heterogeneity in the hypoxic regulation of VEGF. Accordingly, the specific aims of this project are: (1) Analysis of interindividual heterogeneity in hypoxia-inducible VEGF production in patients with obstructive sleep apnea syndrome (OSAS) in vivo and in vitro and its relationship to coronary collaterals; (2) Determination of the molecular mechanism for interindividual heterogeneity in VEGF production in response to hypoxia. These studies may lead to the development of new strategies to increase VEGF production in the setting of ischemic heart disease and thereby promote therapeutic angiogenesis. In addition, understanding the mechanism of interindividual heterogeneity in VEGF production in response to hypoxia would be of tremendous importance for understanding and predicting the natural history of a wide variety of diseases involving VEGF including tumor angiogenesis, diabetic retinopathy, rheumatoid arthritis, and inflammatory bowel disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HYPOXIA-INDUCED AKT SIGNALING MODULE IN NEURONAL CELLS. Principal Investigator & Institution: Gozal, Evelyne; Pediatrics; University of Louisville University of Louisville Louisville, Ky 40292 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2007 Summary: (provided by applicant): The purpose of this proposal is to elucidate hypoxiainduced Akt-related pathways induced in neuronal PC- 12 and RN46A neuronal cells by sustained hypoxia and by intermittent hypoxia, and to determine how these signaling pathways affect cell survival. We will test the hypothesis that hypoxia-induced interactions between different signaling molecules within the Akt signaling module, modulate tolerance or vulnerability to sustained and intermittent hypoxia in neuronal cells. We propose: (1) To identify, using proteomic approaches, members of the Akt

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signaling module in normoxic and hypoxic neuronal cells, and to identify differences in Akt-associated proteins during sustained and intermittent hypoxia; (2) To characterize protein-protein interactions within the Akt signaling modules; (3) To identify selective Akt - protein interactions within the signaling module that underlie neuronal survival to sustained and intermittent hypoxia; (4). To examine the effect of disruption of proteinprotein interactions within the Akt signaling module on downstream genes involved in regulation of hypoxia-induced cellular apoptosis. We will use proteomic techniques, SDS-PAGE and MALDI-MS to identify the Akt-binding proteins coimmunoprecipitating with Akt in normoxic cells or cells exposed to sustained or intermittent hypoxia. Interactions of the components of the Akt signalosomes will be determined by TnT coupled transcription, translation, co-immunoprecipitation, and GST pull-down methods. Transformer kits will be used to make in frame and serial deletion mutants of Akt and its binding proteins in order to identify their Akt docking sites. Finally we will introduce into the cells TAT-fusion peptides corresponding to specific docking sites of targeted proteins binding to Akt signaling module, and disrupt their interaction with the Akt signaling complex to assess the effect of protein association/dissociation with the Akt signaling module, on cell survival to sustained and intermittent hypoxia. These studies will provide the groundwork for future intervention strategies aiming to prevent neuronal cell loss in diseases associated with intermittent and sustained hypoxia, such as sleep apnea and lung disease. 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: INTRACELLULAR ANALYSIS OF AIRWAY MOTONEURONS DURING SLEEP Principal Investigator & Institution: Chase, Michael H.; Professor; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024

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Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 31-AUG-2002 Summary: The clinical signs of obstructive sleep apnea are reflected in abnormal patterns of upper airway motor control. These patterns of control are evidenced by changes in airway patency, which are dependent on the activity of cells that innervate the airway musculature, most specifically hypoglossal and ambiguus motoneurons. The objective of the proposed research is to generate basic data relating to the circuitry, neurotransmitters and neuromodulators responsible for the control of these motoneurons. Intracellular recordings will be obtained from hypoglossal and ambiguus motoneurons; extracellular recording will be obtained by neurons of the medullary motor inhibitory area that provide a monosynaptic inhibitory input to these motoneurons. Electrical stimulation will be applied to the site of REM sleep generation in the pons (the nucleus pontis oralis) to examine the circuitry that controls the excitability of the preceding airway patency motoneurons. The neurochemical control of these motoneurons will be determined by recording from them intracellularly, while simultaneously ejecting neurotransmitter and neuromodulator antagonists and agonists juxta-cellularly. These studies will first be undertaken in an animal model of sleep in which atonia is induced via the pontine microiontophoretic application of carbachol, and subsequently in chronic animals during naturally occurring sleep and wakefulness. The significance of our proposed studies is based upon the following factors. First, in order to understand and treat obstructive sleep apnea, it is essential to clarify the mechanisms that control the activity of airway patency motoneurons. Second, only by recording intracellularly can one differentiate between the two fundamental processes, postsynaptic and presynaptic, that can promote a decrease in motoneuron activity during sleep. In preparation for this application, we recorded intracellularly from hypoglossal motoneurons and found that they are postsynaptically inhibited during REM sleep. This finding, which was obtained by recording with intracellularly-placed microelectrodes, contradicts previous data obtained by indirect means which did not reveal the presence of postsynaptic control during this state. These data therefore suggest that the currently purported airway control mechanisms that operate during sleep need to be reexamined and direct data relating to the state- dependent control of the responsible motoneurons must be developed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MATURATION OF THE HYPOXIC VENTILATORY RESPONSE Principal Investigator & Institution: Bissonnette, John M.; Professor; Obstetrics and Gynecology; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2001; Project Start 15-FEB-2000; Project End 31-JAN-2003 Summary: (Adapted from the Investigator's Abstract): The proposed experiments are designed to test the hypothesis that the lack of hypoxic respiratory depression in mice at P1-P3 results from gamma-aminobutyric acid (GABA), acting at GABAA receptors, depolarizing the resting membrane potential and thereby exciting respiratory neurons at this stage of development. Experiments are proposed in decerebrate and vagotomized mice to show that the greater respiratory drive in P1-P3 mice compared to P7-P10 pups is central in origin. Pharmacologic and genetic techniques will be used to determine the role of GABA in hypoxic hyperpnea and depression during early postnatal development in unanesthetized mice. Whole cell recordings will also be performed in brainstem slices to determine membrane potential and the reversal potential for chloride in the presence of a GABAa agonist. Changes in the chloride potential may underlie disturbances in respiratory drive and apnea in premature human newborns. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MECHANISMS MEDIATING C/V DISEASE IN CHILDREN WITH OSA Principal Investigator & Institution: Amin, Raouf S.; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, Oh 45229 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: (provided by applicant): Obstructive sleep apnea (OSA) is an important clinical disorder occurring in men, women, and children with a prevalence of 4%, 2% and 1-3%, respectively. OSA is under active study in adults and is definitely linked with increased cardiovascular morbidity, even in its mild to moderate clinical forms. In contrast, OSA has not been well studied in children and the potential deleterious consequences on cardiovascular function have received little or no attention. Our goal is to examine in children 1) The interaction between OSA and baroreflex dysfunction, 2) The relation of OSA severity and baroreflex dysfunction to abnormalities in blood pressure control during wakefulness and sleep, 3) The association of the diminished baroreflex gain and impaired blood pressure control with an index of end organ damage, the left ventricular mass index, and 4) Whether effective treatment of OSA results in significant improvement in baroreceptor function, blood pressure control and a decrease in left ventricular mass index. We will accomplish these aims by studying 812 year old children with OSA and a matched group of normal children in a crosssectional design. We will study baroreceptor function, 24-hour ambulatory blood pressure and left ventricular mass index. Baroreceptor function will be measured by non-invasive techniques based on combined computer analysis of heart rate and blood pressure measured by portapres. 24-hour ambulatory blood pressure will be measured by a Spacelab monitor and left ventricular mass index will be measured by direct Mmode echocardiogram. In a longitudinal study we will study the effect of adequate treatment of OSA on baroreceptor function, daytime and nocturnal blood pressure and left ventricular mass index. We will follow a cohort of children with OSA and a matched group of normal controls for a period of 12 months after treatment of the disorder. Results are expected to show that children with OSA have decreased baroreceptor sensitivity, elevated nocturnal blood pressure and increased left ventricular mass index and that effective therapy for OSA, as determined by polysomnography, will improve or normalize baroreceptor sensitivity as well as nocturnal blood pressures and will lead to a decrease in left ventricular mass index. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MENOPAUSE AND MIDLIFE AGING EFFECTS ON SLEEP DISORDERS Principal Investigator & Institution: Young, Terry B.; Professor of Prventative Medicine; Population Health Sciences; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2002; Project Start 15-JAN-1997; Project End 31-DEC-2006 Summary: (provided by applicant): The long-range goals of this ongoing longitudinal study of midlife aging in women are to accurately quantify the associations of menopause with the development and progression of sleep apnea and diminished sleep quality and to identify factors that influence the associations. Understanding the role of menopause in the development of sleep apnea and diminished sleep quality has important clinical and public health significance. Sleep apnea and diminished sleep quality are associated with significant cardiovascular morbidity, depression, and decrements in daytime performance. Because menopause will become a persistent state

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in nearly every woman during her lifetime, even a small effect on sleep apnea and insomnia, the major sleep disorders, would translate into significant morbidity. Furthermore, if associations are causal, understanding whether hormone replacement therapy or other factors significantly modify a menopause-sleep disorder link may lead to interventions that could reduce the occurrence and severity of sleep disorders in midand later life. The proposed study is designed to: 1) Test the hypothesis that changes over the continuum of pre to post menopause increase the incidence and progression of sleep disordered breathing, adjusted for baseline age, body composition, and other potential confounders, 2) investigate the effects of change in body composition during midlife on associations of menopause and sleep apnea, 3) quantify the risk of insomnia, hypersomnia and diminished sleep quality attributable to early, middle and late perimenopause and post menopause, 4) investigate protective effects of hormone replacement therapy on sleep problems, and 5) investigate genetic vulnerability to diminished sleep quality during menopause. To accomplish these aims, we propose additional research on our unique longitudinal cohort of midlife women, with 7-15 years of previously collected polysomnographic and other data with a) new data collected from overnight in-laboratory protocols with polysomnography conducted at 4-year intervals on 621 women enrolled in the Wisconsin Sleep Cohort Study, b) new data collected semi-annually by in-home polysomnography and other procedures and monthly diaries on menstrual characteristics and sleep problems on a subset of 280 women over their pre to peri to post menopausal years. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MENTORED DEVELOPMENT AW

PATIENT-ORIENTED

RESEARCH

CAREER

Principal Investigator & Institution: Gurubhagavatula, Indira Md; Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 01-AUG-2000; Project End 31-JUL-2005 Summary: PROPOSAL (Adapted from the applicant's abstract): Characterized by intermittent airway closure during sleep, OSA is extremely prevalent, afflicting 2-4% of Americans. If left untreated, a large body of evidence convincingly shows that OSA can lead to daytime hypertension. In fact, 20-30% of patients with OSA will have hypertension, and 40% of patients with hypertension have occult OSA. The question then is how to identify patients who have OSA from among this high-risk population of individuals with hypertension. Polysomnography (PSG), the current diagnostic gold standard, is expensive and inconvenient. Several simple techniques to screen for OSA are available: questionnaires, craniofacial measurements, nocturnal oximetry and airflow monitoring devices. However, no one has compared their relative efficacies or costs in one unified population. The investigator proposes to compare these screening tools against full PSG's in a cohort of patients at high risk for OSA, i.e., outpatients with hypertension. Among the cases of OSA subsequently identified, the applicant next proposes to evaluate outcomes of treatment of OSA with continuous positive airway pressure (CPAP) in a randomized, placebo- controlled trial. The specific aims, therefore, are: 1) to compare the accuracy of several screening strategies for OSA in outpatients with hypertension; 2) to determine their relative economic costs; and 3) to determine the effect of CPAP therapy on blood pressure (BP) and sympathetic activity during sleep and awake states in OSA patients with hypertension. These projects are extraordinarily important. They have the potential to lead to dramatic changes in the approach to management of the patient with hypertension. Along with a complementary program of

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didactic training, they will constitute a strong foundation of experience for the applicant in her goal of becoming an independent clinical investigator. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MICROCIRCULATORY EFFECTS OF INTERMITTENT HYPOXIA Principal Investigator & Institution: Johnson, Paul C.; Professor and Head; Bioengineering; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 92093 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-AUG-2004 Summary: The purpose of this study is to test certain hypotheses regarding the acute and chronic effects of intermittent hypoxia on microvascular and parenchymal cell function through in vivo microcirculatory studies. Using the cremaster muscle preparation of the anesthetized rat, Specific Aim 1 will test the hypothesis that reduction of oxygen concentration in the inspired air in the range of 7 percent to 10 percent for 30 s to 3 min duration causes microcirculatory hypoxia and changes in blood flow and vascular tone due to neural influences and local regulatory mechanisms. This aim will also test the hypothesis that chronic episodes of hypoxia alter normal control mechanisms that regulate vascular tone of arterioles in accordance with local oxygen levels; specifically prostaglandins, NO and metabolites of cytochrome P-450. Specific Aim 2 will test the hypothesis that reduction of oxygen in the inspired air causes oxygen levels in tissue surrounding the venous portion of the microvascular network to fall below critical levels, causing a shift in the redox state of mitochondria in the parenchymal cells. This aim will also test the hypothesis that intermittent hypoxia leads to tissue injury and increased expression of venular P-selectin, leukocyte adhesion and rolling oxidative stress, and parenchymal cell injury and death. Since some of the changes seen in sleep hypoxia are neural in origin, a subset of these studies will involve use of unanesthetized animals with an implanted window to study the microcirculation. By reproducing the hypoxic conditions in the microcirculation and tissue like present in sleep apnea, the investigators aim to identify key changes and provide a better rationale for treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MRI OF THE UPPER AIRWAY OF CHILDREN WITH OSAS Principal Investigator & Institution: Arens, Raanan; Children's Hospital of Philadelphia 34Th St and Civic Ctr Blvd Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 20-SEP-1999; Project End 31-JUL-2003 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NASAL OBSTRUCTION AND SLEEP APNEA TREATMENT OUTCOMES Principal Investigator & Institution: Weaver, Edward M.; Otolaryn & Head & Neck Surgery; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: (provided by applicant): Obstructive sleep apnea syndrome is characterized by symptomatic recurrent upper airway obstructions during sleep that may result in serious physiologic abnormalities, medical risks, and quality of life deficits. It occurs in 2 - 4% of adults and is a target disorder for Healthy People 2010. Providing continuous

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positive airway pressure (CPAP) represents first-line therapy. Surgical treatment may serve as an adjunct to CPAP or as a second line definitive therapy, but surgical effectiveness data are lacking. The principal investigator's long-term goal is to evaluate rigorously surgical treatment of the nasal, oral, hypopharyngeal, and laryngeal airways for sleep apnea as an independent investigator. For the period of this award, he proposes to develop sophisticated surgical outcomes research skills through a program of didactics, conferences, focused clinical activity in the Sleep Disorders Center, and hands-on research with the guidance of expert advisors. This research proposal focuses on the role of nasal obstruction, and its surgical correction, as a means of improving clinically important outcomes of CPAP therapy. The specific aims are to: 1. Determine whether nasal obstruction influences CPAP treatment outcomes above and beyond other behavioral and biomedical factors in a prospective inception cohort study. 2. Conduct a pilot trial to examine whether surgical treatment for nasal obstruction improves CPAP outcomes. This single-site pilot trial will provide the principal investigator with clinical trials experience as well as data on logistical, feasibility, and measurement issues for a definitive trial. Future independent investigations of other surgically correctible anatomic abnormalities associated with sleep apnea will follow the model of this proposed research plan. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEURAL SITES MEDIATING OBSTRUCTIVE SLEEP APNEA Principal Investigator & Institution: Harper, Ronald M.; Professor; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 31-AUG-2002 Summary: The objectives are to determine, using functional magnetic resonance (fMRI) techniques, the location and time course of activation of brain structures activated during obstructive sleep apnea. We hypothesize that particular regions of the orbital frontal cortex, rostral hypothalamus, amygdala, locus coeruleus, midline raphe, and dorsal and ventral pons, which activate to simulated obstructive apnea in waking control subjects, will fail to activate, or respond with reduced activity during sleep apnea events of patients, but will continue to activate during simulated obstructive apnea during sleep in controls. Other regions involved in the suppression of muscle tone may show excessive activation in patients, thereby inducing obstructive apnea. A time series of 30 repetitions of 20 image slices across the entire brain will be obtained in the sagittal plane using blood oxygen level dependent (BOLD) Echo Planar-Imaging pulse sequences, optimal for sensing perfusion alterations, in 20 obstructive apnea patients and 20 age- and sex-matched controls during apnea events of sleep (patients) and during inspiratory loads (20 cM water) applied at the onset of an inspiratory effort during sleep (controls). To partition effects of sleep, both groups will undergo a baseline waking recording, followed by inspiratory loading, and Valsalva pressor challengers, which simulate sensory and autonomic aspects of obstructive apnea. Heart rate, flow, non-invasive blood pressure, arm sweating, and digit oximetry will be measured concurrently with image scans. The MR signal changes will be assessed with software optimized for fMRI processing to gauge regional activation changes during apneic events, inspiratory loading and sympathetic challenges. Cross correlations of regional image changes with respiratory, cardiovascular and sympathetic outflow induces will be calculated. The studies have the potential to identify brain regions involved in mediating upper airway atonia, to provide insights into pharmacologic intervention for obstructive sleep apnea, and to determine the neural sites involved in autonomic concomitants of airway obstruction.

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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEUROBEHAVIORAL CONSEQUENCES OF SLEEP APNEA IN CHILDREN Principal Investigator & Institution: Gottlieb, Daniel J.; Associate Professor; Medicine; Boston University Medical Campus 715 Albany St, 560 Boston, Ma 02118 Timing: Fiscal Year 2001; Project Start 20-SEP-1999; Project End 31-JUL-2003 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NEUROMUSCULAR CONTROL OF THE PHARYNGEAL AIRWAY Principal Investigator & Institution: Fregosi, Ralph F.; Associate Professor; Physiology; University of Arizona P O Box 3308 Tucson, Az 857223308 Timing: Fiscal Year 2001; Project Start 10-APR-1998; Project End 31-MAR-2003 Summary: (Adapted from the applicant's abstract): The long-term objective of this proposal is to test the hypothesis that the muscles that protrude and retract the tongue (genioglossus and hypoglossus/styloglossus muscles, respectively) are co-activated during inspiration, and that co-contraction contributes significantly to the maintenance of pharyngeal airway patency. The conceptual model is that co-contraction during inspiration stiffens the tongue as the antagonist muscles work against one another, thereby minimizing backward displacement of the tongue and subsequent occlusion of the pharynx. Significant new data showing respiratory-related co-activation of the protrudor and retractor muscles in animal models, as well as recent evidence showing improved inspiratory airflow with co-activation in human subjects with obstructive sleep apnea, provide strong support for this conceptual framework. Accordingly, the following Specific Aims are designed to rigorously test the co-activation hypothesis using an anesthetized rat model: Aim 1 is to demonstrate that the protrudor and retractor muscles of the tongue are co-activated during breathing and that they respond similarly to changes in respiratory related stimuli. Aim 2 is to show that co-activation of the extrinsic tongue muscles will improve pharyngeal airway mechanics more than the independent activation of either the protrudor or retractor muscles. Aim 3 is to demonstrate that the initial operating length of the tongue muscles will influence: a) the magnitude of respiratory related tongue movements, b) the ability of the tongue muscles to modulate pharyngeal airway flow mechanics, c) the fatigability of the tongue muscles. These experiments will lay the foundation for new and improved treatment strategies for persons with obstructive sleep apnea or with other conditions that are caused by malfunction of the tongue motor system. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NOVEL SYSTEMS TO EVALUATE SLEEP APNEA AND VIGILANCE Principal Investigator & Institution: Levendowski, Daniel J.; Advanced Brain Monitoring, Inc. 2850 Pio Pico Dr, Ste a Carlsbad, Ca 92008 Timing: Fiscal Year 2001; Project Start 01-FEB-2001; Project End 31-JUL-2001 Summary: The proposed research demonstrates the feasibility for two innovative evaluation procedures for diagnostic screening and treatment outcome assessment for sleep apnea (SA). The Alertness for diagnostic screening and treatment outcome assessment for sleep apnea (SA). The Alertness Profiler (AP) combines an easy-to-apply electroencephalographic (EEG) monitoring system and PC-based vigilance, attention

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and memory tests in a 90-minute protocol designed to quantify levels of daytime drowsiness and their effects on performance. The AP will be evaluated with 20 SA patients and 20 health subjects and referenced to a previously collected normative database. The Apnea Risk Evaluation System (ARES) is an integrated system including: a physiological data acquisition device for monitoring SpO2, pulse, snoring and head position, easily self-applied and comfortably worn overnight to screen for SA; software to identify respiratory events and artifacts; a validated questionnaire to assess risk factors commonly associated with SA; and an expert system to classify individuals into five risk levels for SA. During Phase I, the prototype ARES device will be designed and tested on five health subjects. Software development will begin using data from 30 SA patients. The AP and the ARES can be used together or independently to offer accurate, inexpensive and easy to administer tests for the assessment and monitoring of SA. PROPOSED COMMERCIAL APPLICATIONS: An estimated 20 million people in the U.S. suffer from sleep apnea (SA), the majority undiagnosed. The Alertness Profiler and the Apnea Risk Evaluation System (ARES) offer accurate, inexpensive and easily administered procedures for the assessment and monitoring of SA and the measurement of daytime drowsiness. Both products will be marketed to industry, healthcare and epidemiologists. The ARES will also be sold directly to consumers. A searchable database describing SA prevalence, prognosis and outcome will be created with data generated from these products. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NURSING INTERVENTIONS USED IN FEEDING PRETERM INFANTS Principal Investigator & Institution: Hill, Alice T.; Professor; None; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2001; Project Start 01-SEP-2000; Project End 31-AUG-2003 Summary: Learning to suck efficiently is the major work of the preterm infant. Infants who fail to suck efficiently impair their cardiopulmonary functions, impede their behavioral state changes, and fail to gain weight appropriately. Despite the seriousness of these outcomes, there have been only a few published clinical trials of developmental care programs. These trials evaluated infant outcomes related to developmental care in terms of total program effect, making it impossible to evaluate the effects of specific developmental interventions. Therefore, the specific aims of this project are to: (a) determine the degree of physical growth (weight gain, increases in length and occipitofrontal head circumference) and behavioral state change (sleep/wake) immediately following a one week intervention program and a 7-day follow-up, and (b) describe the process by which physical growth and behavioral state change occur in regard to selected indicators of sucking efficiency (heart rate, respiratory rate, oxygen saturation levels, and sucking pattern characteristics). A 4 group, repeated observation, control group design of inefficient feeders will be used. Each group will consist of 55 infants for a total of 220 subjects. Group I infants will receive oral support (cheek and jaw support), Group II infants will receive nonnutritive sucking (pacifier), Group III will receive a combination of oral support and nonnutritive sucking, and Group IV will serve as the control group. RM-ANCOVA and ANOVA will be the statistical methods used to address the four hypotheses. It is essential that we understand the outcomes of specific interventions with bottle feeding over time, since (a) many of the complications (e.g., apnea, bradycardia, oxygen desaturation, untoward changes in behavioral state changes, and changes in sucking pattern characteristics) experienced by preterm infants occur during and immediately after the feeding session and (b) weight gain and the

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absence of apnea or bradycardia are major criteria used by neonatologists and neonatal nurse practitioners to discharge infants from the hospital. If proven to be effective strategies, these techniques could potentially shorten the length of hospital stay for the preterm infant resulting in cost-saving benefits for the hospital. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OBESITY AND NEURAL CONTROL IN SLEEP DISORDERED BREATHING Principal Investigator & Institution: Smith, Philip L.; Professor of Pulmonary Medicine; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001; Project Start 20-JAN-1987; Project End 31-AUG-2003 Summary: (Applicant's abstract): Sleep disordered breathing is characterized by upper airway obstruction and hypoventilation during sleep. Obstructive sleep apnea is the most common form of sleep disordered breathing, and is due to recurrent collapse of the upper airway during sleep. The major risk factors for the development of sleep disordered breathing are obesity, male gender, and increasing age. The precise mechanism for upper airway obstruction and hypoventilation during sleep are unknown. Currently, it is believed that these events are due to alterations in mechanical factors or neuromuscular control precipitated by obesity. It is our overall hypothesis that obesity is associated with progressive defects in reflex mechanisms that lead to upper airway obstruction and hypoventilation during sleep. Moreover, we have evidence that weight loss ameliorates sleep disordered breathing, and we now wish to determine whether this improvement is due to restoration of reflex control mechanisms in the human and to determine the neurohumoral mechanisms in a murine model of the syndrome. In a series of cross sectional and longitudinal experiments, we will examine the effects of obesity on upper airway and ventilatory function, and its modulation by weight loss. In Specific Aim 1, we hypothesize that the response in upper airway pressure-flow relationships to electrical stimulation of the hypoglossal nerve is more effective (a) when the locus of collapse is in the oropharyngeal region and (b) in patients with a lower body mass index. In Specific Aim 2, we hypothesize that a defect in reflex responses to nasal pressure and CO2 exists in (a) patients with obstructive sleep apnea vs. normal controls, and (b) that this defect depends upon the degree of obesity. In Specific Aim 3, we hypothesize that weight loss will restore reflex responses to nasal pressure and CO2. In Specific Aim 4, we hypothesize that (a) changes in neuroventilatory control with weight loss requires an intact leptin axis, and (b) the protective effect of leptin is enhanced in females vs. males. This proposal develops and utilizes methods specifically to quantitate the mechanical and neuromuscular basis for disturbances in upper airway neuromuscular control in humans (Specific Aims 1-3). Complementary experiments in a murine model are proposed in order to probe neurohumoral mechanisms responsible for alterations in ventilatory control (Specific Aim 4). The proposed studies are designed to elucidate the pathophysiologic basis and to explore novel treatments for sleep disordered breathing. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: OBSTRUCTIVE SLEEP APNEA IN CHILDREN Principal Investigator & Institution: Glaze, Daniel G.; Associate Professor Pediatrics & Neurolo; Pediatrics; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2001; Project Start 20-SEP-1999; Project End 31-JUL-2003 Summary: This abstract is not available.

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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OSA AND METABOLIC SYNDROME: ROLE OF OXIDATIVE STRESS Principal Investigator & Institution: Sanders, Mark H.; Medicine; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2007 Summary: (provided by applicant): The Metabolic Syndrome (Met. Syn.) has been defined as insulin resistance (I.R.), central obesity, systemic hypertension and dyslipidemia and is associated with increased cardio/cerebrovascular (CV) risk. I.R. may mediate much of this risk. Obstructive Sleep Apnea-Hypopnea (OSAH) is also associated with augmented CV risk and I.R. and plausibly, the CV risk of OSAH is mediated through I.R. Since OSAH is associated with both Oxidative Stress (O.S.) and pro-inflammatory processes, and O.S. is associated with I.Ro, it follows that O.S. and inflammation may link OSAH to I.R. and the Met. Syn. The Overall Goal of this research is to test the hypothesis that O.S and Inflammation link OSAH to I.R. as well as other CV risk-promoting conditions reflecting Met. Syn. We will specifically test if individual sleep consequences of OSAH, including Sleep Fragmentation and Intermittent Sleep Hypoxia, promote O.S. and Inflammation which in turn promote I.R. and other features of the Met. Syn. We propose: Specific Aim: la: To determine the effect of Sleep Fragmentation on O.S. and Inflammation and to explore the relationships between O.S. and Inflammation and I.R., dyslipidemia, sympathovagal tone and plasma cortisol, we will measure the following study variables: I.R., lipid profile, circulating & exhaled biomarkers of O.S., pro-inflammatory cytokines, plasma cortisol, & heart period variability before and after 2 consecutive nights with experimentally induced Sleep Fragmentation in normal subjects.Aim lb: To assess interaction between i) pre-existing Met. Syn., and ii) the overweight condition without Met. Syn., with regard to the effects of Sleep Fragmentation on the study variables, we will contrast the effect of experimentallyinduced sleep disruption in: non-OSAH/overweight individuals/(+)Met. Syn., non-OSAH/overweight individuals/(-)Met. Syn. and a control group of nonOSAH/normal weight/(-)Met. Syn.;Aim: 2: To evaluate the effect of Intermittent Sleep Hypoxia on O.S. and Inflammation and explore the relationships between O.S. and Inflammation and I.R., dyslipidemia, sympathovagal tone and plasma cortisol. OSAH patients on chronic positive airway pressure (PAP) therapy will have biomarkers of O.S., Inflammation and the other above study variables, measured under two conditions in random order: i) before and after 2 consecutive nights using PAP therapy but with experimentally induced Sleep Fragmentation (fragmentation+normoxia), ii) before and after 2 nights without PAP (fragmentation+hypoxia) to evaluate for an independent Intermittent Sleep Hypoxia effect.; Aim: 3: Using microarray data from peripheral monocytes, we will explore if specific gene expression profiles after the study conditions are associated with alterations consistent with Met. Syn. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PAIN, OPIOIDS, AND SLEEP IN CANCER PATIENTS Principal Investigator & Institution: Alley, Linda G.; Adult and Elder Health; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 31-MAR-2006 Summary: (provided by applicant) Medical oncology patients experiencing pain frequently report nocturnal sleep disturbances and daytime sleepiness that adversely affect their functional health status (FHS) and quality of life (QOL). Furthermore, sleep

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disturbances may lead to increased subjective sensations of pain. Opioid analgesics are known to have intrinsic properties that negatively affect sleep quality. However, they can exert a positive effect on sleep by relieving pain. Therefore, pain and opioids can be viewed as two factors independently affecting nighttime sleep daytime wakefulness while also interacting with each other. The purposes of this descriptive comparative study are to examine pain and opioid use in relation to sleep and wakefulness and to examine associations between daytime and nocturnal sleep and FHS and QOL. The sample will include 80 medical oncology subjects who take opioid analgesics for cancer related pain and report a daily worst pain score or 6 on a scale of 10. All subjects who meet the entrance criteria will be screened by one night of laboratory-based polysomnography to eliminate those with severe periodic leg movement disorder or sleep apnea syndrome. Those subjects meeting all criteria to continue in the study will undergo a laboratory based multiple sleep latency test the following day to index subjects' physiological sleepiness as well as complete brief pain and sleep surveys and QOL and FHS inventories with documented reliability and validity. Subjects will then be monitored for one 48 hour period in their usual home environments via ambulatory polysomnographic equipment and will make entries in a pain and sleep diary. The study will examine the extent to which pain intensity and opioid use are independently associated with day and night time sleep as well as the relationships between sleep and wakefulness and FHS and QOL. Given the centrality of opioids to cancer pain management, detailed analyses of the associations between pain and opioids and sleep and wakefulness in medical oncology patients are needed to develop optimal treatment regimens that maximize the benefits of pain relief while minimizing side effects of sleep disruption. Finally, the results of the study will assist in furthering the development of theory regarding sleep regulatory processes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PATHOGENESIS AND GENETICS OF OBSTRUCTIVE SLEEP APNEA Principal Investigator & Institution: Schwab, Richard J.; Professor; Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 08-APR-2002; Project End 31-MAR-2007 Summary: Although sleep disorders have been identified by the NIH as an area with tremendous scientific growth potential there are a paucity of patient oriented investigators studying sleep-related questions. The University of Pennsylvania is fortunate to have internationally recognized faculty and a strong infrastructure to support high quality patient-oriented research and training m sleep disorders. This infrastructure includes: Center for Sleep and Respiratory Neurobiology, Center for Clinical Epidemiology and Biostatistics, General Clinical Research Center, 3 Sleep Training Grants and the Pulmonary Imaging Group. Dr. Schwab is an integral part of each of these programs and is highly committed to a career in patient-oriented sleep research, proposing to study the genetics and biomechanical basis for obstructive sleep apnea. Dr. Schwab has made seminal observations about changes in the upper airway in patients with sleep apnea and he has successfully mentored several pulmonary fellows and junior faculty. Dr. Schwab through funding from this K24 can further develop into an academic leader and train others investigators that the sleep field desperately needs. Specifically this award would allow Dr. Schwab to develop further expertise in new radiologic techniques in upper airway imaging and computer-based volumetric analysis; further his expertise in genetic epidemiology and bioinformatics; allow increased time for mentoring young scientists and for developing new areas of collaboration with scientists. Dr. Schwab has developed a state-of-the-art upper airway

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imaging program focusing on understanding the pathogenesis and treatment of obstructive sleep apnea. Recently, Dr. Schwab has begun to apply his upper airway imaging expertise to study phenotypic risk factors for sleep apnea. He is the first to apply advanced quantitative MR Imaging techniques and novel volumetric computer image analysis techniques to study the genetic basis for sleep apnea. The scientific portion of this grant will utilize upper airway imaging to study both the pathogenesis and genetics of sleep apnea. My specific aims are: 1) to evaluate and compare upper airway soft tissue structural and biomechanical properties in apneics and normal weight-matched controls during wakefulness and sleep; 2) to quantify upper airway craniofacial structure, soft tissues and regional fat deposition using three dimensional magnetic resonance imaging in order to determine the intermediate traits associated with obstructive sleep apnea utilizing a case control design in normals and apneics; and 3) to determine the upper airway structural risk factors for sleep apnea that demonstrate family aggregation and are most likely to have a genetic component by comparing probands, siblings of probands, neighborhood controls and siblings of neighborhood controls. To address these specific aims, we have planned a logical series of studies that will provide insight in the pathogenesis of obstructive sleep apnea and the anatomic risk factors for this condition. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PATIENT INTERFACE FOR CONTINUOUS POSITIVE AIRWAY PRESSUR Principal Investigator & Institution: Kayyali, Hani A.; Program Director; Biomec, Inc. 1771 E 30Th St Cleveland, Oh 44114 Timing: Fiscal Year 2001; Project Start 01-MAY-2001; Project End 31-OCT-2001 Summary: (Verbatim from the Applicant's Abstract) Obstructive Sleep Apnea (OSA) affects 12 million people. It is caused by frequent closure of the upper respiratory airway obstructing breathing during the night. Nasal Continuous Positive Airway Pressure (NCPAP) is the most effective OSA treatment; it opens the airways by creating positive pressure in a nasal mask. Although treatment is efficacious and relatively straightforward the diagnostic study to prescribe it (CPAP titration) remains inconvenient and costly. CPAP titration studies are conducted overnight in the hospital, which is expensive. Hospitals are also overcrowded, and the unfamiliar setting causes many patients to lose sleep thus preventing accurate pressure titration. This approach discourages enlisting, and is partly responsible for the disproportionately low numbers of OSA patients who are treated (1 million out of the estimated 12 million). The home is a more natural setting and holds great potential in addressing the existing patient demand. It is more convenient and cost effective but current ambulatory devices are unsuited for in-home CPAP titration. They rely on traditional patient interfaces that are unreliable and generate signal quality that is often compromized by patient movement. This discourages patients from using and physicians from prescribing in-home studies. Phase I will demonstrate feasibility of a novel patient interface that utilizes miniaturized wireless pressure and airflow sensors embedded in the mask, and wireless transmission of biopotential data (EEG, EKG,.) with a compact Bio-amplifier. We will construct a prototype of the proposed interface and compare it with conventional approaches. Phase II will develop the commercial patient interface and a recording unit with modem capability for on-line remote monitoring between the home and the clinic. PROPOSED COMMERCIAL APPLICATION: There is a huge potential market for this device. Out of the estimated 12 million people who suffer from OSA only 1 million patients are treated leaving a huge demand that is unmet. The proposed device will expand treatment by

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allowing patients to be diagnosed at home; thus help raise total sales of respiratory products such as masks, monitors,. etc. The sleep apnea products segment of the respiratory devices market posted revenues of $122 million in 1996. The commercial potential for the proposed device is not only for home use but the new patient interface can also benefit traditional in-lab studies because it improves patient mobility without compromising data integrity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PATTERNED HEMODYNAMIC RESPONSE TO AROUSAL FROM SLEEP Principal Investigator & Institution: Weiss, J Woodrow.; Co-Director; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 31-AUG-2002 Summary: Patients with obstructive sleep apnea (OSA) experience repetitive nocturnal oscillations that occur in association with changes in respiration and changes in sleep state. The highest heart rate and arterial pressure of the apnea-recovery cycle occur at apnea termination, co-incident with both the nadir of oxygen saturation and arousal, an abrupt disruption of sleep. But the relative contributions of chemo- stimulation using a unique porcine model of airway occlusion during sleep, we have begun to isolate the hemodynamic consequences of chemo-stimulation from those of sleep disruption by defining regional changes in blood flow in response to arousal induced by respiratory and non-respiratory stimuli. Data gathered in this laboratory using porcine model lead us to propose a series of interrelated hypothesis: 1) airway obstruction during sleep, when associated with abrupt sleep disruption, typically causes a patterned cardiovascular responses, with regional blood flow changes consisting of hindlimb vasodilation and visceral vasoconstriction; 2) we further hypothesize that arousal, an abrupt disruption of sleep is necessary to initiate hindlimb vasodilation and renal vasoconstriction after respiratory and non-respiratory stimuli during sleep; 3) the patterned cardiovascular response to airway occlusion during sleep is, like the cardiovascular defense reaction, effected through sympathetic activation, and is independent of cardiovascular reflex responses (baroreflex, chemoreflex). We will make measurements of blood flow in iliac, renal, mesenteric, and coronary arteries in animals awake and sleep. In these animals we will use tracheal occlusion and acoustic and tactile stimuli to induce respiratory and non-respiratory arousals. We are interested in determining whether the hemodynamic response to airway occlusion has critical, defining features of the cardiovascular defense reaction, and further, in understanding what physiologic factors modify this response. We believe that these studies will importantly influence our understanding of the cardiovascular consequences of arousal and will promote greater understanding of the contribution of OSA to cardiovascular morbidity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PHARMACOLOGY OF SLEEP APNEA Principal Investigator & Institution: Hendricks, Joan C.; Professor; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 31-AUG-2002 Summary: Considerable evidence suggests that a reduction in the serotoninergic (5- HT) excitatory input to upper airway motoneurons during sleep plays a major role in the depression of their activity thus permitting airway closure. If this is so, then

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manipulating the 5-HT system to endure the maintenance of 5-HT levels at these motoneurons during sleep, and/or using selective 5-HT agonists to excite these motoneurons, could provide a pharmacotherapy for obstructive sleep apnea. This concept is the basis of this proposal. Supporting evidence comes from recent studies using our animal model of obstructive sleep apnea, the English bulldog. We systematically administered a combination of trazodone and L-tryptophan, thought to increase 5-HT levels and provide agonist activity at these motoneurons. The treatment reduced sleep-disordered breathing in a dose- dependent fashion. However, the doses of trazodone required were higher than those currently employed in humans. Further development of a 5-HT pharmacotherapy requires knowledge of the specific 5-HT receptor subtypes involved in the excitatory effect at the motoneuron to choose selective agonists. Additionally, the relative efficacy of different strategies to increase 5-HT levels at upper airway motoneurons needs to be determined. For each of these two approaches to increase the 5-HT excitation of the upper airway motoneurons during sleep, we will pursue complementary studies in two animal models. Anesthetized rats will be used in Specific Aim 1 for direct microinjection studies into the hypoglossal (XII) motor neurons to elucidate the specific 5-HT receptors mediating excitation using pharmacological probes; and in Specific Aim 3 to examine the effect of different 5-HT-enhancing drugs on XII activation. These studies provide basic information about the pharmacology in a normal mammal. The English bulldog will be used to document whether, in this animal with congenital airway narrowing, antagonists directed at specific 5-HT receptors suppress airway dilating muscle activity and cause airway collapse during waking (Specific Aim 2), and whether drugs that increase 5-HT relieve sleep- disordered breathing (Specific Aim 4). These projects are thus designed to specifically address basic pharmacological mechanisms of the role of 5-HT in controlling upper airway motoneuronal activity, but with the practical goal of developing a pharmacotherapy for this common disorder. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PHARYNGEAL MECHANICS BY TAGGED MRI IN A ZUCKER RAT MODEL Principal Investigator & Institution: Brennick, Michael J.; Ctr for Sleep and Respiratory Neurobiology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): The goal of the proposed research is to develop the technical, physiological and analytical techniques in advanced magnetic resonance imaging (MRI) to track tissue motion in the pharyngeal walls of anesthetized rats in order to establish a small animal model of pharyngeal airway mechanics. The model is relevant to the pathophysiology of obstructive sleep apnea, a prevalent respiratory disorder in humans characterized by the repetitive closure of the pharyngeal airway during sleep. Previous studies on the control of pharyngeal airway patency have been generally limited to measurements of airway size, shape, and collapsibility. Consequently, our understanding of the mechanical properties of the pharyngeal wall tissues that affect these airway changes is very limited. For example, although it is known that body mass index is the most important predictor of OSA, and that obesity is associated with an increase in airway collapsibility, we do not yet understand how obesity alters the mechanical properties of pharyngeal wall tissues to effect these changes. To address these gaps in our knowledge, the PI will adapt a novel magnetic resonance imaging (MRI) tissue tagging technique in anesthetized rats called spatial modulation of magnetization (SPAMM(r), developed at the University of Pennsylvania)

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to quantify pharyngeal wall tissue motion, i.e., tissue movement and tissue strain, and quantify how pharyngeal wall tissue motion produces changes in airway size and shape. We propose to develop novel technology that will enable us to examine pharyngeal wall tissue motion in anesthetized obese and non-obese Zucker rats, the obese genotype having a compromised pharyngeal airway similar to that in patients with OSA. Specific Aim 1 is to develop the techniques needed to use MRI with SPAMM to quantify pharyngeal wall tissue motion during spontaneous breathing in anesthetized, non-obese and obese Zucker rats under hyperoxic and hypoxic conditions. Specific Aim 2 is to develop the techniques needed to use MRI with SPAMM to quantify pharyngeal wall tissue motion in non-obese and obese Zucker rats during selective electrical stimulation of the hypoglossus nerve, and its branches that supply motor output to tongue protrudor (medial branch) and retractor (lateral branch) muscles. The global hypothesis for Aims 1 and 2 is that obesity compromises pharyngeal airway patency by reducing cross-sectional area and putting the pharyngeal muscles at a mechanical disadvantage. Our development of innovative methods to track tissue motion in the pharyngeal walls will reveal new insights into pharyngeal mechanics that increase our understanding of the role of obesity in the pathophysiology of OSA. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: POSTNATAL BRAIN SUSCEPTIBILITY TO INTERMITTENT HYPOXIA Principal Investigator & Institution: Gozal, David A.; Professor and Vice-Chair for Research; Pediatrics; University of Louisville University of Louisville Louisville, Ky 40292 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: (provided by applicant): Obstructive sleep apnea syndrome (OSA) is a frequent condition affecting up to 2 percent of the pediatric population at ages that are characteristically associated with dynamic brain development and acquisition of important neurocognitive functions. OSA is characterized by repeated episodes of hypoxia during sleep, and when untreated it is associated with significant neurocognitive morbidities such as excessive restlessness and irritability, diminished intellectual performance, attention span, learning and vigilance. However, the relative contributions of chronic intermittent hypoxia (CIH) to OSA-associated neurocognitive dysfunction in children remain unclear. In adult rats, a CIII profile that mimics the intermittent hypoxia observed in patients with OSA during sleep leads to substantial reductions in spatial learning and retention as well as diminished ability to induce longterm potentiation in the CA1 region of the hippocampus. These neurobehavioral and physiological alterations correlate with anatomical changes developing in corticohippocampal regions., and we have found that such anatomical changes are particularly prominent in developing rat pups at post-natal ages that coincide with the peak prevalence of USA in children, suggesting that this period of brain maturation is uniquely vulnerable to CIH. We therefore hypothesized that the detrimental effects of CIH on memory and learning performances during this highly vulnerable developmental period are long-lasting, and will be manifest even during adulthood, long after the CIH exposure has ceased. Furthermore, these neurocognitive deficits will be associated and correlated with parallel electrophysiological alterations in the characteristics of long-term potentiation (LTP) of the CAl region of the hippocampus, as well as with disruption of normal ionotropic glutamate receptor expression and binding characteristics within the cortex and hippocampus. We propose to: (1) examine the short-term and long-term consequences of CIH on behavioral patterning and on water

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maze task acquisition and retention. (2) To assess the short-term and long-lasting effects of CIH on LTP characteristics of the CA1 region of the hippocampus.; (3) To establish changes in NMDA glutamate receptor expression and binding characteristics in neocortical and hippocampal regions associated with CIH, and following long-term recovery; (4) To determine whether exposure to CIH during a critically-vulnerable period of development will elicit time-dependent glial and neuronal stem cell proliferation within cortical and hippocampal regions. These studies will characterize concomitant structural and phenotypic changes induced by CIH in a developmental rodent model of OSA, and provide initial insights into the role of CIH in short-term and long-term neurobehavioral morbidity of USA in children. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: POSTNATAL RESETTING OF CAROTID CHEMORECEPTOR SENSITIVITY Principal Investigator & Institution: Carroll, John L.; Associate Professor; Arkansas Children's Hospital Res Inst Research Institute Little Rock, Ar 72202 Timing: Fiscal Year 2001; Project Start 01-AUG-1995; Project End 31-AUG-2004 Summary: The main sensors of arterial oxygen (02) tension are the carotid bodies (CB). Although they are critically important during infancy, they are not fully developed at birth, and take time to mature. The site of O2 sensing is believed to be the type I cell, which depolarizes in response to hypoxia, leading to Ca2+ influx through calcium channels, a rise in intracellular calcium and release of neurotransmitters which are thought to stimulate carotid sinus nerve endings. We previously reported that the type I cell calcium response to hypoxia matures after birth, and our recent studies suggest that several aspects of this cascade change after birth, as follows: (a) depolarization of type I cells by hypoxia is minimal in cells from newborns and increases with age; (b)the O2sensitivity of a background K+ conductance is small in cells from newborns and increases with age; and (c) calcium currents of immature, but not mature, type cells are inhibited 50% by hypoxia. The proposed work will test the hypothesis that developmental changes in the O2-sensitivity of a background "leak" K+ conductance account, in part, for postnatal maturation of carotid chemoreceptor O2 sensitivity. In addition, we will determine whether (1) background K+ conductance is carried by one major background K+ channel type, the O2 sensitivity of which increases with age; or (2) background K+ conductance in type I cells is carried by at least 2 channel types, one O2sensitive and one non-O2-sensitive, and development involves a change in the ratio of the O2-sensitive to non-O2-sensitive channels. We will also seek to understand whether developmental shifts occur in 0a-sensitive calcium channels during maturation. The results will answer important questions about the mechanisms underlying postnatal development of carotid chemoreceptor function. The ultimate goal of the proposed studies is to understand how the carotid chemoreceptors mature and how development is modulated, so that a number of potentially life threatening disorders such as asthma, bronchopulmonary dysplasia, apnea and sudden infant death syndrome (SIDS) can be better treated or prevented. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PRECISE CONTOL OF TONGUE MOVEMENT Principal Investigator & Institution: Goldberg, Stephen J.; Professor; Anatomy and Neurobiology; Virginia Commonwealth University Richmond, Va 232980568 Timing: Fiscal Year 2001; Project Start 01-JUN-1994; Project End 31-MAY-2006

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Summary: The normal development of the complex neuromuscular system used to control tongue movement is critical to the immediate survival of all terrestrial mammals. Voluntary control in this motor system involves a sequence of neural and muscular events beginning in the motor cortex. Coordinated tongue movements are needed for eating (mastication and swallowing), drinking, licking (suckling), breathing, grooming and vocalization. Clinically, and in contrast to a normal developmental progression, premature human infants often need to be fed intravenously or with a nasogastric tube for extended periods of time (weeks or months) to insure their survival. Attempts to begin bottle feeding these infants can result in apnea, bradycardia, hypoxia, fatigue and agitation and there can also be the long term consequence of delayed oral feeding milestones which results in longer hospital stays. A later impact on motor speech has also been documented. It may be that the interrupted normal maturation of the neuromuscular control system for appropriate suckling plays an important role here. In addition, infants born at term who also need non-oral nutrition due to system disorders or surgical interventions may also exhibit delayed oral feeding. We propose, therefore, to continue our studies of rat hypoglossal nucleus anatomy and tongue muscle contractile measures with a new emphasis on system development. We also propose to add morphological and biochemical studies of individual developing tongue muscles. The normal development of this system, and its cortical control, will then be compared and contrasted to that in rat pups who have been fed, for varying postnatal times, using a gastric cannula. Some animals will experience a near total absence of suckling while others will have their normal suckling sequence interrupted. This has been termed "artificial rearing" and is modeled on the human infant interventions mentioned above. New preliminary data indicates that artificial rearing from postnatal days 4 to 13 results in striking changes in tongue contractile strength, speed, endurance, muscle fiber diameter and a persistence of developmental myosin heavy chain (MHC) isoforms, similar to changes observed in other skeletal muscles after a period of disuse. These studies should help to lay a firm foundation for an understanding of how the hypoglossal motor system develops, especially since many aspects of its normal development have simply not yet been studied. In addition, we hypothesize that the neuroanatomical organization within the hypoglossal nucleus, muscle morphology plus MHC expression, muscle contractile characteristics and afferent input from the motor cortex are altered in animals that have been artificially reared. The degree to which each of these components is altered needs to be ascertained for a clearer view of this motor system and to delineate those postnatal time periods that are the most critical for normal development. It is also hoped, for the long run, that these basic findings can have an application for a speedier and more complete rehabilitation of human infants that are necessarily deprived of normal suckling and eating. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PREVALENCE OF SLEEP DISORDERED BREATHING IN CHILDREN Principal Investigator & Institution: Bixler, Edward O.; Professor; Psychiatry; Pennsylvania State Univ Hershey Med Ctr 500 University Dr Hershey, Pa 17033 Timing: Fiscal Year 2001; Project Start 01-AUG-2001; Project End 31-JUL-2006 Summary: (provided by applicant): The objectives of this proposal are to: 1) establish the prevalence of different types of sleep disordered breathing (SDB) in a large general random sample of children; 2) identify important risk factors of SDB; (3) establish the family history of various risk factors associated with children with SDB; (4) assess the impact of SDB on clinical, psychometric and behavioral/academic outcomes; and 5) identify characteristics which will assist in identifying those children at risk for SDB for

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possible early intervention. Several studies evaluating select populations have suggested that various severe consequences are associated with SDB in children. These consequences include: cardiovascular complications such as pulmonary hypertension, cor pulmonale, and arrhythmia; behavioral abnormalities such as excessive daytime sleepiness, poor school performance, hyperactivity, aggressive behavior, and social withdrawal; and growth disturbances which at times are reversed by successful treatment. To date, there have been only four studies evaluating the prevalence of sleep apnea using objective sleep evaluation methods in general random samples of children. Three studies evaluated a limited age range of 6 mos to 6 yrs, while the fourth assessed a range of 2-18 years. These studies employed relatively small samples in their sleep laboratory phase (N=lO, 11, 132, and 126, respectively). Thus, they could not adequately assess clinical significance. None of these studies evaluated: general development (eg height, weight, age adjusted BMI); the effects of SDB on physical health (eg blood pressure); academic achievement; or electrophysiologic defined sleep stages as possible outcome measures. Only one study reported a possible association with daytime sleepiness and behavior. Thus, the prevalence and clinical impact of SDB in school age children is unknown. In order to establish the prevalence and clinical significance of SDB in children aged 6 - 12 years with reasonable precision, we propose to employ a protocol similar to that used to establish the prevalence and clinical significance in two previously NIH supported protocols in adults. The proposed study will employ a twophase protocol: 1) questionnaire completed by the parents of every child enrolled in local elementary school which will assess general sleep, behavior and learning problems; 2) a random sample (n= 1,000) selected from the first sample based on risk for SDB and evaluated in the sleep laboratory to determine the presence of SDB. The second phase will receive a thorough pediatric ENT and pulmonary evaluation and school records and behavior will be assessed. The parents of this group will be interviewed for the family history of risk factors associated with SDB in children. This strategy will yield adequate power to establish the prevalence and clinical significance of SDB in children. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROGESTERONE AND SLEEP IN OLDER WOMEN Principal Investigator & Institution: Moe, Karen E.; Psychiatry and Behavioral Scis; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2002; Project Start 01-FEB-2002; Project End 31-DEC-2004 Summary: Sleep complaints increase significantly with age in women. Many older women experience difficulty falling asleep, more night-time awakenings, and less restful sleep. Sleep studies verify that disturbed sleep patterns are observed even in healthy older women. Sleep disturbances are associated with increased daytime drowsiness, increased accident risk, increased use of health care, and reduced quality of life. Older women receive a disproportionate number of sedative-hypnotic medications, which can exacerbate sleep apnea and have daytime carryover effects such as sedation, falls and subsequent fractures, and cognitive impairment. A better understanding of the sleep changes experienced by older women is sorely needed. One contributing factor may be menopause-related changes in sex steroids such as estrogen and progesterone. Research attention has focused on estrogen. However, progesterone may also participate in the control of sleep. Clinical reports indicate that women often feel drowsy after they take oral progesterone - an effect which is undesirable during the day, but may be positive at night. To date there are no published studies of progesterone's effect on the objectivelymeasured sleep and daytime drowsiness of older women. The proposed study will take a systematic, multi-dimensional approach to determining the effect of progesterone on

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the sleep and drowsiness of older women. Objective techniques (polysomnography, Multiple Sleep Latency Test) will be used to measure sleep and daytime drowsiness following evening or morning administration of 300 mg micronized progesterone, in 40 postmenopausal women who are at least 5 years past menopause and who are not experiencing hot flashes. Attention, memory, subjective sleepiness, and blood levels of progesterone and its metabolite (allopregnanolone) will also be measured. This study is part of a long-term research plan to assess (1) how the very low postmenopausal levels of estrogen and progesterone contribute to sleep difficulties of older women, and (2) how hormone replacement therapy affects the sleep of women. An ongoing placebocontrolled study is investigating the effects of estrogen on the sleep of older women. The proposed study will complement the estrogen study. It will enhance our limited understanding of the relationship between sex steroids and sleep, and the factors that contribute to sleep problems in older women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROTECTIVE VENTILATORY RESPONSES TO HYPOXIA Principal Investigator & Institution: St. John, Walter; Professor; Children's Hospital (Boston) Boston, Ma 021155737 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2002 Summary: The protective response to hypoxia is organized in two layers. With initial exposure, eupneic ventilation increase. In severe hypoxia, eupnea is replaced by gasping, which promotes "autoresuscitation." The eupneic ventilatory response to hypoxia changes with development. In the newborn, ventilation rises and then falls. With age, the hypoxia- induced augmentation becomes more sustained. We hypothesize that hypoxia- induced ventilatory depression results from activation of a mesencephalicpontine "central oxygen detector." Piglets will be studied. We will identify the region containing the "central oxygen detector." Hypoxia-induced depressions of ventilation will be attenuated if neurons of this central oxygen are destroyed. Neuronal activities of this detector will be characterized. These activities are hypothesized to increased during depressions of phrenic activity in hypoxia or during localized hypoxia by applications of sodium cyanide. We will then examine the role of neurons in the ventral medulla in hypoxia-induced ventilatory depressions and in the neurogenesis of gasping. These ventral medullary neuronal activities may provide a generalized tonic input for ventilatory activity. Yet gasping will not be altered since the mechanisms underlying the neurogenesis of eupnea and gasping differ fundamentally. In unanesthetized piglets, ventilatory activity will be recorded during wakefulness and sleep. We hypothesize that apneic episodes will be recorded following ablation of neurons in the medullary gasping center and those in the ventral medulla. Our results will have profound implications as to the mechanisms of apnea and the sudden infant death syndrome. Mechanisms of central apnea may be elucidated by our studies of the "direct" influence of hypoxia on the brainstem ventilatory control system, of the role of ventral medullary mechanisms in this hypoxia-induced depression and the role of medullary gasping mechanisms in the control of eupnea. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PULMONARY HYPERTENSION FOLLOWING INTERMITTENT HYPOXIA Principal Investigator & Institution: Fagan, Karen A.; Medicine; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508

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Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2007 Summary: (provided by applicant): Pulmonary hypertension (PHTN) is common in diseases characterized by chronic hypoxia (CH) (i.e. COPD, IPF) and occurs in 15-40% of patients with sleep apnea. Intermittent hypoxia (IH) mimicking the hypoxiareoxygenation cycles of sleep apnea causes systemic hypertension and altered regulation of systemic vascular tone. However, the effect of intermittent hypoxia on the pulmonary circulation is unknown. Recently, patients with sleep apnea-induced PHTN were found to have exaggerated hypoxic pulmonary vasoconstriction. Unlike in chronic hypoxia, hypoxia in sleep apnea is not continuous, thus the mechanisms causing sleep apnea-induced PHTN are likely different from chronic hypoxia-induced PHTN. We therefore hypothesize that intermittent hypoxia leads to pulmonary hypertension by differential expression of genes important in regulating pulmonary vascular tone. Specifically, we hypothesize that oxidant stress in IH increases NOS and decreases SOD leading to PHTN through increased formation of peroxynitrite thus decreasing NO available for cellular effects such as attenuating vasoconstriction and mediating vasodilation. We further hypothesize that IH activates redox sensitive transcription factors leading to differential lung gone expression compared to CH. We will present data showing IH-induced PHTN in both rats and mice. We also will present data showing differential expression of NOS (nitric oxide synthase) and SOD (superoxide dismutase) in the lung following IH compared to CH, which may contribute to IHinduced PHTN through increased oxidant stress and decreased NO activity. This proposal will address the questions: 1) does repetitive hypoxia-reoxygenation causes pulmonary hypertension, 2) that despite increased NOS, NO appears to be insufficient to prevent IH-induced PHTN, 3) decreased SOD may contribute to IH-induced PHTN by increasing oxidant stress and formation of peroxynitrite, and 4) does IH leads to differential gene expression through activation of specific signaling pathways compared to CH. We will correlate physiologic measures of PHTN and pulmonary vascular tone with expression and activity of NOS and SOD, measurements of oxidant stress and NO, and activation of specific signaling pathways leading to altered gone expression in IH. This proposal, for the first time, will identify the consequences of IH in the pulmonary circulation. Understanding mechanisms contributing to the development of PHTN in IH may lead improved cardiovascular morbidity and mortality in this common disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION OF GENE EXPRESSION IN INTERMITTENT HYPOXIA Principal Investigator & Institution: Czyzyk-Krzeska, Maria F.; Associate Professor; Molecular and Cellular Physio; University of Cincinnati 2624 Clifton Ave Cincinnati, Oh 45221 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-AUG-2004 Summary: Obstructive sleep apnea (OSA) is a relatively common disorder that is characterized by repetitive episodes of upper-airway obstruction that occur during sleep and cause repetitive episodes of oxygen desaturation of arterial blood (hypoxia). Chronically, OSA syndrome can result in a number of serous cardiovascular problems including systemic arterial hypertension. There is evidence that the OSA-induced hypertension is neurogenic, that it emanates from the oxygen chemoreceptor cells in the carotid body, and involves the catecholaminergic cells within the peripheral sympathetic nervous system and adrenal medulla. This application proposes that intermittent hypoxia stimulates gene expression in these tissues, and that this may be involved in the pathogenesis of hypertension associated with OSA. This is supported by

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the previous finding that brief periods (<1hr) of sustained hypoxia stimulates expression of several genes in the oxygen-sensitive type 1 cells of the carotid body, including tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine synthesis. Enhanced catecholamine biosynthesis in the sympathetic nervous system is a potential mechanism for hypertension. The present research will test the hypothesis that very brief episodes (20 sec) of re-occurring hypoxia are sufficient to increase gene expression in the carotid body, superior cervical ganglion, and the adrenal gland. It is hypothesized that intermittent hypoxia regulates gene expression in these tissues and results in the OSA-induced hypertension. Specific Aim 1 will focus on the characterizing the effects of intermittent hypoxia on a known hypoxia- regulated gene that has been implicated in hypertension, namely TH and some of its known transcriptional regulators, including cfos, junB, and CREB. This aim will also test the hypothesis that gene expression induced by intermittent hypoxia in the superior cervical ganglion and adrenal gland requires synaptic input that originates in the carotid body. It is further hypothesized that coordinate regulation of many genes and proteins mediates the cellular response to such a complex stimulus as intermittent hypoxia. This possibility will be explored in Specific Aim 2, which will focus on identifying the gene and protein expression pattern in the carotid body, superior cervical ganglion and adrenal gland using unique cDNA libraries and high-throughout genomics (cDNA microarray) and proteomics (2-D protein gels and mass spectrometer) analysis. The findings from this study may provide new insight concerning the role of intermittent hypoxia on regulation of gene expression and possible targets for mediating the pathogenesis of OSA-induced hypertension. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RESPIRATORY PERIDOCITY AND COGNITIVE DECLINE IN ELDERS Principal Investigator & Institution: Carlson, Barbara W.; None; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-DEC-2006 Summary: Laboratory and clinical findings suggest that states of low cerebral oxygenation are associated with cognitive decline and dementia in older adults. Sleep is a period of increased risk for hypoxic events; and low respiratory periodicity may be an important indicator for identifying individuals with low cerebral oxygenation during sleep. Our previous studies suggest that older adults with low respiratory periodicity have more fragmented sleep, more low amplitude delta sleep and greater declines in cerebral oxygenation during sleep. The aims of this longitudinal observational study are (1) to examine the relationship between measures of respiratory periodicity, sleep structure and cerebral oxygenation during sleep; (2) to examine whether respiratory periodicity or cerebral oxygenation during sleep, alone or in combination, predict cognitive decline over 24 months; and (3) to explore how changes in respiratory periodicity and cerebral oxygenation change over 24 months. One hundred and six community dwelling older adults, age 70+ years, will be evaluated at baseline and at 12and 24-months. Respiratory periodicity will be measured from the respiratory inductance plethysmograph waveform and include the average 5- minute measures of the variability in the duration (sdIBI), frequency (sdIBF) and amplitude (sdAMP) of breathing cycles. Standard polysomnographic methods will be used to measure sleep structure, which include the proportion of sleep states, as well as the mean interval between sleep spindles, sleep-wake transitions, arousals, and K-complexes. Dual (rightleft) cerebral oximetry will be used to measure maximum change in the average 5minute right and left cerebral oxyhemoglobin saturation from resting awake baseline.

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Standardized tests of secondary memory, working memory, and attention will be measured at the same time as the sleep studies in order to describe changes in cognitive function and to examine whether respiratory periodicity or cerebral oxygenation alone or in combination predict cognitive decline over 24 months. In addition, we will explore how respiratory periodicity and cerebral oxygenation change and interact over time. Data on sleep quality, cerebrovascular risk factors, physical activity and depressive symptoms will be measured every 6 months because these measures can change rapidly and may affect the key outcome measures. In addition to serving as a comparison group, data from subjects who do not exhibit cognitive decline will be used in exploratory analyses to determine gender and race-associated differences in respiratory periodicity and cerebral oxygenation. Since little is known about respiratory periodicity or cerebral oxygenation using cerebral oximetry in older adults, this prospective study will provide important data for determining how these variables vary and may be used to predict cognitive decline in a carefully screened sample of older adults. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RURAL DWELLING OLDER ADULTS: CPAP ADHERENCE SUPPORT Principal Investigator & Institution: Smith, Carol E.; Professor; None; University of Kansas Medical Center Msn 1039 Kansas City, Ks 66160 Timing: Fiscal Year 2001; Project Start 01-APR-2000; Project End 31-MAR-2005 Summary: Obstructive Sleep Apnea (OSA) is the most prevalent and costly sleep disorder in essentially healthy older adults. OSA is assoicated with cardiovascular and neurocognitive sequaela and with public safety losses due to traffic fatalities and other accidents that cost 43 to 56 billion dollars annually (National Commission Sleep Report, number 1, 1993). OSA is controlled with nightly Continuous Positive Airway Pressure (CPAP) ventilation, the treatment of choice (National Commission on Sleep Report number 2, 1994). The primary aim of this randomized clinical trial is to determine the long-term adherence, health, quality of life outcomes, and cost-benefit of a comprehensive intervention on CPAP ventilation in 168 rural dwelling older adults with OSA. Adherence is measured by microprocessor pressure-sensor timer/recorder as patient hours of nightly CPAP use. The Secondary Aim is to assess relationships among CPAP adherence, quality of life, family caregiving, use of a decision aid for driving safety and accidents. The intervention was derived from Triandis and Smith models and each intervention step has been tested in older adults. The intervention steps gradually increase in intensity from self-directed and focused counseling to in home 2-way telehealth monitoring that allows a nurse to direct CPAP care and assess for physical and emotional barriers to adherence and internet interaction. Intervention steps in this proposed study are administered per criteria only if the patient is not adhering to the prescribed CPAP treatment. The steps use music and focused imagery for CPAP habit initiation and sensitization to physiologic and affective benefits from CPAP and mobilizing the family to overcome barriers to CPAP use. Through the internet, subjects connect to peer and professional counselors, engage in interactive adherence support activities, obtain accurate information when seeking unproven cures and use decision aids for driving. An established Univ. of Ks. multidisciplinary team will conduct the study with a subcontract with the Univ. of Wisc. The long-term goal of this proposed study is to validate a CPAP adherence support system that will ultimately improve patient and family caregiver quality of life and public safety, as well as reduce patient and family caregivers' morbidity and the 100 billion dollars spent annually on nonadherence. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SELF-DISPENSING RESPIRATORY EFFORT BAND Principal Investigator & Institution: Schoess, Jeffrey N.; Korosensor.Com, Inc. 3421 50Th St, Ne Buffalo, Mn 55313 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-MAR-2003 Summary: (provided by applicant): Korosensor proposes to develop an innovative "sensor-on-tape" technology to accurately detect apnea conditions for sleep study patients of all age groups. A self dispensing respiratory effort band is a medical device, which incorporates strain-sensitive polymer sensing capability. The self dispensing band reduces false alarms related to central, mixed and obstructive apnea by improving respiratory event registration, and providing tape like sleep patient fitting. Korosensor's approach to demonstrating self-dispensing effort band monitoring has evolved from research working with polymer thick film (PTF) conductive elastomer materials, polymer films, ink jet printing and low power analog instrumentation technology. PTF technology offers the benefits of low cost manufacturing using ink jet printing methods with elastomer materials to provide conforming comfort for sleep study patients. The proposed self dispensing respiratory effort band system will permit a home monitor patient to easily install the effort band to clearly and confidently score subtle apnea and respiratory effort related arousal's (RERA). A 1.0-mil thick apnea sensitive transducer will be incorporated into the effort band using a polymer thick film circuit and a polymer film layer to sense apnea problems. A simple set of amplifier support electronics will measure and condition effort band data for recording on a physiological recorder or Internet home-based monitoring system. PROPOSED COMMERCIAL APPLICATIONS: The self-dispensing respiratory effort band is proposed to provide cost-effective respiratory monitoring of sleep patients. Fabricating respiratory effort bands with sensor-on-tape technology will improve respiratory data consistancy and detection of subtle apnea. Pro-Tech Services, Inc., a leading supplier of sleep disorder products is partnered with Korosensor in the development effort. Pro-Tech provides a clear path for commerical production after completing a successful phase II effort. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ENRICHMENT

SHAPING

HEALTH

BEHAVIORS

THROUGH

SCIENCE

Principal Investigator & Institution: Campfield, L. Arthur.; Department Head and Professor; Food Science & Human Nutrition; Colorado State University Fort Collins, Co 80523 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-AUG-2003 Summary: (Adapted from the applicants abstract): The epidemic of obesity in children and adolescents is a major challenge in the prevention and medical management of obesity. It is serious and alarming because being overweight or obese as a child or adolescent greatly increases the risks for chronic diseases such as type 2 diabetes, heart disease, sleep apnea, stroke, joint pain and some cancers. The increasing number of obese children and adolescents will lead to a large increase in the number of adult obese Americans. Obesity affects at least 25 percent of all adolescents in the United States with young Hispanic Americans and African Americans at higher risk. A strong relationship has been shown between childhood and adult obesity: One third of obese preschoolers and more than one half of obese grade school kids become obese adults. A Science Education Partnership is proposed to promote obesity prevention in Colorado. The Program on Obesity of the Center for Human Nutrition will partner with the Department of Preventive Medicine in the School of Medicine and the School of Nursing

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at UCHSC, Det of Food Science and Human Nutrition at Colorado State University, the Culinary Arts Program of Johnson & Wales University in Denver. These university groups will also work collaboratively with the major science museums in Denver: the Museum of Natural History, the Children's Museum, and Botanic Garden. The Partnership will aim to reduce the rate of childhood and adolescent obesity in Colorado by introducing science and math enrichment programs in elementary schools as well as science museum-based and school-based programs directed at middle and high school students and the community. These programs will provide interactive, "hands-on", fun, and challenging educational science enrichment using examples and exercises from food, nutrition, healthy eating, physical activity and the biology of body weight regulation. Internet-based technology will be used for many lessons, activities and data collection on health behaviors and knowledge of students. All programs will include elements on obesity-its causes, health impacts, and prevention. These model programs will be evaluated by: a) determining the rate of weight and body mass index (BMI) gain of individual students; b) improvement in science-based health knowledge; and c) improvement in health behaviors in individual elementary school students. In addition, we propose to establish and provide leadership for a partnership of interested organizations within Colorado to plan, develop, implement and support a public health campaign. The goal of the campaign will be to prevent obesity and enhance health through the promotion of active lifestyles and healthy eating with a special focus on changing the behavior of children and their families. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SLEEP APNEA IN ELDERLY MALE TWINS Principal Investigator & Institution: Carmelli, Dorit; Sr. Biostatistician/Epidemiologist; Sri International 333 Ravenswood Ave Menlo Park, Ca 94025 Timing: Fiscal Year 2000; Project Start 01-AUG-1998; Project End 31-JAN-2004 Summary: The contribution of genetic factors to sleep disorders has been demonstrated in twin and family studies, and further understanding of the genetic underpinning of sleep disorders is considered an important area of research. Many of the suggested risk factors for sleep apnea (e.g., craniofacial morphology, obesity) have genetic determinants. However, a formal genetic analysis of these anatomical risk factors with sleep-recorded physiological measurements has not so far been conducted. The objective of the proposed study is to conduct such an analysis in a well-characterized U.S. population-based registry of elderly male twins who have been successfully followed for the past 30 years. Specifically, we propose: (1) to recruit a subsample of 150 pairs from the NAS-NRC World War II Twin Registry in which at least one of the twin brothers reported sleep apnea symptoms and a subsample of 30 control pairs in which both twins reported no symptoms; (2) monitor the subgroup of 180 twin pairs with overnight sleep recording; (3) collect on these subjects anthropometric measurements of weight, height, neck circumference, and craniofacial morphology; and (4) collect blood samples for determination of zygosity and DNA extraction for future molecular studies. The twin design is most powerful for estimating the genetic and/or environmental overlap between physiological measurements such as sleep-recorded disordered breathing, obesity, and craniofacial morphology. We have chosen to focus on an elderly male twin sample for which a wealth of data relevant to this study has been previously collected. Twin pair concordance or discordance for monitored sleep-disordered breathing will allow the full characterization of genetic/familial and individual environmental factors associated with the expression and severity of this condition. The investigators of this study represent a multidisciplinary team who have the knowledge

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and experience to conduct a comprehensive genetic study of sleep-disordered breathing in the only existing and well-studied U.S. twin registry of elderly men. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SLEEP APNEA IN LOOK AHEAD PARTICIPANTS Principal Investigator & Institution: Foster, Gary D.; Associate Professor of Psychiatry; Psychiatry; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-JUL-2006 Summary: (provided by applicant): Weight loss is a frequently recommended treatment for obese patients with obstructive sleep apnea (OSA). The empirical support for this recommendation is lacking. Based on descriptive studies, weight loss appears to improve but not abolish sleep disordered breathing. Moreover, the degree of improvement in OSA is quite variable and not directly proportional to weight loss. The lack of randomized trials, the study of predominantly male samples, and the absence of follow-up evaluations leave physicians and patients unsure about the utility of weight loss treatment in obese OSA patients. The research proposed in this application will assess the effects of weight loss on sleep disordered breathing in 120 obese, Type 2 diabetics with OSA (RDI greater than or equal to 15) who are randomly assigned to either weight loss (n=60) or usual care (n=60) treatments within the context of the Look AHEAD study. Home polysomnography studies will be performed before treatment and at 1 and 2 years. Among the 60 weight loss subjects, we will assess the relative importance of changes in neck and abdominal fat in explaining the variability of changes in sleep disordered breathing after weight loss. Finally, we will examine the relationship between changes in sleep-disordered breathing and changes in blood pressure after weight loss in the 60 weight loss participants. Specifically, this research will: 1) determine the efficacy of a weight loss program in reducing sleep disordered breathing in obese Type 2 diabetics; 2) identify sources of variability in sleep disordered breathing associated with weight loss; and 3) examine the role of sleep disordered breathing in mediating changes in blood pressure associated with weight loss. The results of this study will provide an empirical basis for making recommendations about the effectiveness of weight loss in Type 2 diabetics with OSA. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SLEEP METABOLISM

DISORDERED

BREATHING,

APOE

AND

LIPID

Principal Investigator & Institution: Mignot, Emmanuel J.; Director; Psychiatry and Behavioral Sci; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2002; Project Start 21-SEP-2002; Project End 31-JUL-2006 Summary: (provided by applicant): Recent findings suggest interrelationships between obstructive sleep apnea, lipid metabolism, and neurodegeneration. Apolipoprotein E epsilon4 (APOE e4), a genetic marker linked to increased cardiovascular disease (CVD) risk and Alzheimer's disease (AD), is associated with a two fold increased risk of sleep disordered breathing (SDB), and an increase in severity of apnea symptoms. Preliminary data suggest that this association is stronger between the ages of 50 and 65. Other experiments suggest dysregulated leptin levels in obstructive sleep apnea (OSA). Taken together, these findings suggest common pathophysiological mechanisms involving dysregulated lipid metabolism in OSA. An understanding of these mechanisms is essential for the prevention and treatment of SDB. In this project, we will: 1) extend our finding that APOE e4 increases the risk of sleep apnea in the general population using

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case/control and family designs; 2) examine if polymorphisms in other genes regulating lipid levels are associated with sleep apnea; 3) study the relationship between lipid regulatory gene polymorphisms, lipid profile (LDL- cholesterol, HDL-cholesterol, triglycerides), plasma leptin (and other lipid regulatory hormones), and sleep apnea levels. These studies will be critical to extend our understanding of the association between sleep apnea and the metabolic syndrome. This application will focus on one arm of this complex equation, the relationship between lipid metabolism and SDB. With lipid metabolism being critical to cardiovascular risk, this application will also trigger further studies focusing on cardiovascular impact with adequate control of SDB. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SLEEP, METABOLIC, AND CARDIOVASCULAR DYSFUNCTION IN PCOS Principal Investigator & Institution: Ehrmann, David A.; Associate Professor; Medicine; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-JUL-2007 Summary: (provided by applicant): Polycystic ovary syndrome (PCOS) affects 5-10% of women and may be viewed as the combination of hyperandrogenism with the classical features of the metabolic syndrome in young women. PCOS presents a unique opportunity to dissect the relationship between metabolic and cardiovascular risk and sleep disordered breathing (SDB) in a population where intrinsic effects of aging have not yet developed. Because a relationship between obstructive sleep apnea, insulin resistance and elevated testosterone levels has also been observed in men and in women without PCOS, insights gained from studies in PCOS will have broad implications. the Specific Aims of the present application are: Specific Aim 1: to test the hypothesis that sleep disturbances are caused by hyperandrogenemia and hyperinsulinemia that characterize PCOS. Following a detailed baseline evaluation of sleep, hormonal, metabolic and cardiovascular parameters, women with PCOS will be randomized to an 8-week treatment phase with pioglitazone or depot leuprolide plus estrogerdprogestin replacement or placebo. Pioglitazone will reduce insulin levels, and consequently androgen levels, in PCOS. We will compare the effects of androgen reduction alone (depot leuprolide plus estrogerdprogestin) to those of insulin plus androgen reduction achieved with pioglitazone. Primary comparisons will be the change in sleep parameters from baseline between: placebo & pioglitazone; placebo & leuprolide/estrogen/progestin; pioglitazone & leuprolide/estrogen/progestin. Specific Aim 2: to test the hypothesis that sleep disturbances cause the hormonal, metabolic and cardiovascular alterations seen in women with PCOS. PCOS women with SDB and matched control women with SDB will be evaluated at baseline and following 8 weeks of CPAP treatment. The primary comparison will be between baseline and posttreatment parameters in PCOS women. The secondary comparison will be the posttreatment change from baseline between PCOS and control women to test the hypothesis that for the same degree in improvement in SDB, the magnitude of change in metabolic and cardiovascular measures will be greater in PCOS than in controls. Specific Aim 3: to test the hypothesis that in normal young women, experimental manipulation of sleep that recapitulates the sleep disturbances characteristic of women with PCOS will result in metabolic, hormonal, and cardiovascular alterations that are typical of the metabolic syndrome. A group of healthy young women will be studied twice using a randomized cross-over design. In one study, REM sleep will be fragmented by experimentally induced microarousals for 3 consecutive nights and non- REM sleep will be left undisturbed. In the other, slow wave activity will be suppressed without

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awakening the subject and REM sleep will be left undisturbed. Each study will be preceded by 2 nights of basetine sleep. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SPINAL MECHANISMS OF GUSTATORY INDUCED ANALGESIA Principal Investigator & Institution: Dubner, Ronald; Professor; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2006 Summary: Persistent pain is a serious problem in premature, newborn and young infants. Although it is now known that neonates and young infants exhibit increased pain sensitivity, the fear that anesthetic agents produce respiratory depression, apnea and hypotension in newborns persists clinically and leads to an insufficient control of pain. Of importance for the future management of pain in newborns is the finding in rat pups and human infants that gustatory and orotactile stimulation access endogenous analgesic systems and lead to pain relieving and calming effects. The purpose of this project is to study the underlying mechanisms of gustatory stimulation-induced analgesia and anti-hyperalgesia. Our major hypotheses is that gustatory stimulationinduced analgesia and anti-hyperalgesia in rat pups is mediated, in part, via supraspinal descending pathways that modulate hyperexcitability at the level of the spinal dorsal horn. We will use a model of inflammatory hyperalgesia in rats because it mimics the persistent response to tissue injury produced by surgical intervention and traumatic injury in newborn humans. Correlative histochemical, pharmacological, molecular and physiological studies will be performed to determine the CNS mechanisms involved in the gustatory stimuli-produced behavioral analgesia and anti- hyperalgesia. Aim 1 will examine the postnatal time course of the effects of intraoral sucrose on paw withdrawal responses and test the hypothesis that these effects re mediated by brain stem descending pathways. Aim 2 will test the hypothesis that the behavioral analgesic and anti- hyperalgesic effects of intraoral sucrose involved opioid and monoaminergic mechanisms at the level of the spinal cord. Aim 3 will determine that sucrose-induced analgesia and anti-hyperalgesia suppress spinal dorsal horn neuronal activity and that this effect is produced by activation of descending modulatory systems. Aim 4 will determine the differential mechanisms by which intraoral sucrose modulates the response properties of dorsal horn neurons before and after inflammation. Aim 5 will extend the observations in Project #4 and test the hypothesis that gustatory stimulation in the newborn exposed to cutaneous and visceral inflammation projects against the development of altered nocifensive behaviors in the adult. These studies will lead to a better understanding of the development of analgesic mechanisms and will provide new clinical approaches for activating endogenous mechanisms in newborns. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: THE METABOLIC SYNDROME IN PEDIATRIC OBSTRUCTIVE APNEA Principal Investigator & Institution: Waters, Karen A.; Children's Hospital at Westmead Locked Bag 4001 New South Wales, Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-JUL-2006 Summary: (provided by applicant): This project will evaluate the association between obstructive sleep apnea (OSA) in childhood, and the presence of the "metabolic syndrome". Our aims are: 1. To confirm the association between OSA in children and the presence of known risk factors for future cardiovascular disease. 2. To confirm that the

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physiological disruptions caused by OSA can induce the same metabolic abnormalities in an animal model, and 3. To confirm that treatment of OSA can reverse the abnormalities underlying the metabolic syndrome. The metabolic syndrome is a combination of hypertension, insulin resistance, and dyslipidemia. The first abnormality to appear in children is insulin resistance. The presence of insulin resistance in children has been associated with development of all three abnormalities in adulthood, and thus with increased risk for later cardiovascular disease. Studying OSA in children provides a unique opportunity to study the mechanisms underlying the association between OSA, the metabolic syndrome, and cardiovascular disease. The majority of children with OSA are NOT obese, so it is possible to determine the relative contribution of factors including obesity, chronic sympathetic activation, and chronic inflammation, if a sufficiently large group is studied. Children who present to a sleep unit already have some combination of symptoms suggestive of OSA. Therefore, a parallel study will seek to understand the earliest associations between OSA and the metabolic syndrome. To do this, piglets will be exposed to repetitive hypercapnic hypoxia, and equivalent studies of metabolic abnormalities will be undertaken. This component of the study will examine the specific sequence of disturbances underlying the metabolic syndrome, with the goal of determining preventative strategies that could be translated into the clinical setting. Finally, children who have OSA will undergo treatment, followed by re-evaluation. If treatment of OSA can reverse the metabolic disturbances present in association with OSA, this will support the need for early and aggressive intervention in childhood OSA. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THE ROLE OF CYTOKINES IN SLEEPINESS AND SLEEP APNEA Principal Investigator & Institution: Vgontzas, Alexandros N.; Professor; Psychiatry; Pennsylvania State Univ Hershey Med Ctr 500 University Dr Hershey, Pa 17033 Timing: Fiscal Year 2001; Project Start 01-AUG-2000; Project End 31-JUL-2004 Summary: (applicant's abstract): Excessive daytime sleepiness (EDS) is a major public health concern, in part because individuals suffering from EDS often are not productive at work, are more susceptible to accidents, and generally are unable to function normally during the day. EDS is one of the major manifestations of individuals suffering from obstructive sleep apnea (OSA) and is frequently reported by obese individuals without sleep apnea. The mechanisms underlying EDS observed in both types of these individuals are not clear. We have recently demonstrated that the pro-inflammatory and fatigue-inducing cytokines, tumor necrosis factor-alpha (TNFalpha) and interleukin-6 (IL-6), assayed in single plasma samples, are elevated in subjects with disorders of EDS. In addition, in preliminary studies, we demonstrated that these two cytokines are elevated in obese, compared to lean subjects, and that both sleep disturbance and obesity contribute to the cytokine elevation. More recently, we showed that daytime plasma levels of IL-6 are elevated in experimentally-induced EDS by the use of sleep deprivation and that a good night's sleep is associated with decreased daytime levels in healthy young subjects. There is a large literature implicating several pro-inflammatory cytokines in the regulation of sleep in animals; however, cytokine research on sleep in humans has been very limited. The fundamental hypothesis to be tested by the proposed studies is that the pro-inflammatory cytokines, TNFalpha and IL-6, are associated with and may contribute to EDS. We will test this hypothesis by determining the circadian secretory patterns of TNFalpha and IL-6 in plasma obtained from subjects that exhibit EDS associated with OSA or obesity. Also, we will determine whether nighttime nasal CPAP reduces daytime plasma TNFalpha and IL-6 concentrations in sleep apneics. In addition, we will experimentally induce EDS in healthy young subjects

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by the use of total sleep deprivation or one week of sleep restriction, which mimics real life-situations, to determine the relationship between the pattern of daytime plasma TNFalpha and IL-6 concentrations and daytime sleepiness as measured objectively using MSLT. Finally, we will assess the effects of daytime napping, in healthy subjects, on post-nap sleepiness and TNFalpha and IL-6 secretion. In these studies, we will use a series of experimental techniques including nighttime polysomnography, MSLT, computerized EEG, actigraphy, 24-hour blood sampling, 24-hour recording of core body temperature, and assays for TNFalpha and IL-6. These studies collectively will provide additional evidence for a role of TNFalpha and IL-6 in EDS and lay the foundation for the development of potential therapeutic interventions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: VASCULAR CONSEQUENCES OF SYMPATHETIC NEURAL ACTIVATION IN OBESITY Principal Investigator & Institution: Haynes, William G.; Associate Professor; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2003; Project Start 21-JAN-2003; Project End 31-DEC-2007 Summary: The mechanisms underlying the association between obesity and hypertension are unclear, but increased sympathetic neural drive to skeletal muscle circulation and kidney has been implicated. This insight has been derived from direct intraneural recordings of sympathetic nerve activity and regional norepinephrine turnover. It has been assumed that the increases in sympathetic nerve activity (SNA) directly translate into elevated sympathetic vasoconstrictor tone, but these assumptions have not been rigorously tested. We have recently obtained preliminary data using maximal alpha-adrenergic receptor blockade of the forearm vasculature that demonstrates no increase in sympathetic vascular tone in normotensive obese humans despite increased muscle SNA. This suggests that there is dissociation between sympathetic neural outflow and sympathetically mediated vasoconstrictor tone. Interestingly, we also have preliminary data indicating that in obese hypertensive humans, increased muscle SNA is associated with increased sympathetic vasoconstrictor tone. This suggests that a predisposition to hypertension interacts with obesity to permit the increased SNA to be expressed as increased sympathetic vascular tone. This project will test the hypothesis that the vasoconstrictor effects of SNA are attenuated in obesity but preserved in obese humans with a predisposition to hypertension, with these specific aims: 1) What are the effects of hypertension, obstructive sleep apnea and visceral adiposity on the resistance vessel expression of elevated SNA? 2) Is endothelial nitric oxide generation responsible for attenuated effects of SNA on vascular tone in obese compared to lean normotensive humans, and is the modulating influence of nitric oxide attenuated in obese hypertensive humans? 3) What are the effects of different dietary components on SNA and sympathetically mediated vasoconstrictor tone in obese normotensive and hypertensive subjects? Sympathetic nerve traffic to skin and skeletal muscle will be assessed by microneurography. Sympathetic vasoconstrictor tone will be assessed by the vasodilator response of skin (laser Doppler flux) and skeletal muscle (oxygenation measured by near infra-red oximetry) to intra-arterial infusion of an alpha-adrenergic antagonist. These studies should provide new insights into the cardiovascular effects of obesity and the factors that predispose to obesity-related hypertension. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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

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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 “apnea” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for apnea in the PubMed Central database: •

Choline acetyltransferase mutations cause myasthenic syndrome associated with episodic apnea in humans. by Ohno K, Tsujino A, Brengman JM, Harper CM, Bajzer Z, Udd B, Beyring R, Robb S, Kirkham FJ, Engel AG.; 2001 Feb 13; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=29374

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Obstructive sleep apnea and vascular disease. by Lanfranchi P, Somers VA.; 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=64798

The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with apnea, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “apnea” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for apnea (hyperlinks lead to article summaries): •

3 4

A 54-year-old man with obstructive sleep apnea. Author(s): Kuna ST. Source: Jama : the Journal of the American Medical Association. 2002 October 23-30; 288(16): 2032-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12387656&dopt=Abstract

Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.

With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print. 6 PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.

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A case-control study on psychological symptoms in sleep apnea-hypopnea syndrome. Author(s): Yue W, Hao W, Liu P, Liu T, Ni M, Guo Q. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 2003 June; 48(5): 318-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12866337&dopt=Abstract

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A decision rule for diagnostic testing in obstructive sleep apnea. Author(s): Tsai WH, Remmers JE, Brant R, Flemons WW, Davies J, Macarthur C. Source: American Journal of Respiratory and Critical Care Medicine. 2003 May 15; 167(10): 1427-32. Epub 2003 January 24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12738600&dopt=Abstract

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A model to facilitate outcome assessment of obstructive sleep apnea. Author(s): Sonnad SS, Moyer CA, Patel S, Helman JI, Garetz SL, Chervin RD. Source: International Journal of Technology Assessment in Health Care. 2003 Winter; 19(1): 253-60. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12701956&dopt=Abstract

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A randomized trial of temperature-controlled radiofrequency, continuous positive airway pressure, and placebo for obstructive sleep apnea syndrome. Author(s): Woodson BT, Steward DL, Weaver EM, Javaheri S. Source: Otolaryngology and Head and Neck Surgery. 2003 June; 128(6): 848-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12825037&dopt=Abstract

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A simple method to identify sleep apnea using Holter recordings. Author(s): Stein PK, Duntley SP, Domitrovich PP, Nishith P, Carney RM. Source: Journal of Cardiovascular Electrophysiology. 2003 May; 14(5): 467-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12776861&dopt=Abstract

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Abnormal vasoactive hormones and 24-hour blood pressure in obstructive sleep apnea. Author(s): Moller DS, Lind P, Strunge B, Pedersen EB. Source: American Journal of Hypertension : Journal of the American Society of Hypertension. 2003 April; 16(4): 274-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12670743&dopt=Abstract

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Acceleration of cerebral blood flow velocity in a patient with sleep apnea and intracranial arterial stenosis. Author(s): Behrens S, Spengos K, Hennerici M. Source: Sleep & Breathing = Schlaf & Atmung. 2002 September; 6(3): 111-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12244490&dopt=Abstract

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Additional points for apnea discussion. Author(s): Stebleton J, Doggett J. Source: Adv Nurse Pract. 2001 September; 9(9): 24; Author Reply 24. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12420475&dopt=Abstract

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Ambulatory electrocardiographic monitoring to screen for sleep apnea: is it really that simple? Author(s): Gillis AM. Source: Journal of Cardiovascular Electrophysiology. 2003 May; 14(5): 474-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12776862&dopt=Abstract

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Anatomic and physiologic predictors of apnea severity in morbidly obese subjects. Author(s): Fogel RB, Malhotra A, Dalagiorgou G, Robinson MK, Jakab M, Kikinis R, Pittman SD, White DP. Source: Sleep. 2003 March 15; 26(2): 150-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12683472&dopt=Abstract

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Apnea spells in an infant with vallecular cyst. Author(s): Tibesar RJ, Thompson DM. Source: The Annals of Otology, Rhinology, and Laryngology. 2003 September; 112(9 Pt 1): 821-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14535569&dopt=Abstract

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Apnea, sudden infant death syndrome, and home monitoring. Author(s): Committee on Fetus and Newborn. American Academy of Pediatrics. Source: Pediatrics. 2003 April; 111(4 Pt 1): 914-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12671135&dopt=Abstract

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Apnea-related heart rate variability in congestive heart failure patients. Author(s): Tateishi O, Shouda T, Sakai T, Honda Y, Mochizuki S, Machida K. Source: Clinical and Experimental Hypertension (New York, N.Y. : 1993). 2003 April; 25(3): 183-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12716080&dopt=Abstract

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Apneas, hypopneas, and respiratory effort-related arousals: moving closer to a standard. Author(s): Lewis KL. Source: Current Opinion in Pulmonary Medicine. 2002 November; 8(6): 493-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12394155&dopt=Abstract

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Application of lingual tonsillectomy to sleep apnea syndrome involving lingual tonsils. Author(s): Suzuki K, Kawakatsu K, Hattori C, Hattori H, Nishimura Y, Yonekura A, Yagisawa M, Nishimura T. Source: Acta Otolaryngol Suppl. 2003; (550): 65-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12737346&dopt=Abstract

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Arterial blood gases during diving in elite apnea divers. Author(s): Muth CM, Radermacher P, Pittner A, Steinacker J, Schabana R, Hamich S, Paulat K, Calzia E. Source: International Journal of Sports Medicine. 2003 February; 24(2): 104-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12669255&dopt=Abstract

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Association between sleep apnea and reactive astrocytes in brainstems of victims of SIDS and in control infants. Author(s): Sawaguchi T, Franco P, Kato I, Shimizu S, Kadhim H, Groswasser J, Sottiaux M, Togari H, Kobayashi M, Takashima S, Nishida H, Sawaguchi A, Kahn A. Source: Forensic Science International. 2002 September 14; 130 Suppl: S30-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12350298&dopt=Abstract

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Association of systematic head and neck physical examination with severity of obstructive sleep apnea-hypopnea syndrome. Author(s): Zonato AI, Bittencourt LR, Martinho FL, Junior JF, Gregorio LC, Tufik S. Source: The Laryngoscope. 2003 June; 113(6): 973-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12782807&dopt=Abstract

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Available techniques for objective assessment of upper airway narrowing in snoring and sleep apnea. Author(s): Faber CE, Grymer L. Source: Sleep & Breathing = Schlaf & Atmung. 2003 June; 7(2): 77-86. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12861487&dopt=Abstract

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Behavioral and pharmacologic therapy of obstructive sleep apnea. Author(s): Magalang UJ, Mador MJ. Source: Clinics in Chest Medicine. 2003 June; 24(2): 343-53. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12800788&dopt=Abstract

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Benefit of atrial pacing in sleep apnea syndrome. Author(s): Garrigue S, Bordier P, Jais P, Shah DC, Hocini M, Raherison C, Tunon De Lara M, Haissaguerre M, Clementy J. Source: The New England Journal of Medicine. 2002 February 7; 346(6): 404-12. Erratum In: N Engl J Med 2002 March 14; 346(11): 872. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11832528&dopt=Abstract

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Bilateral leg edema, pulmonary hypertension, and obstructive sleep apnea: a crosssectional study. Author(s): Blankfield RP, Zyzanski SJ. Source: The Journal of Family Practice. 2002 June; 51(6): 561-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12100781&dopt=Abstract

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Binswanger's disease: its association with hypertension and obstructive sleep apnea. Author(s): Matthews KD, Richter RW. Source: J Okla State Med Assoc. 2003 June; 96(6): 265-8; Quiz 269-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12858817&dopt=Abstract

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Blood levels of vascular endothelial growth factor in obstructive sleep apneahypopnea syndrome. Author(s): Gunsilius E, Petzer AL, Gastl GA. Source: Blood. 2002 January 1; 99(1): 393-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11783437&dopt=Abstract

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Blood pressure elevation associated with sleep-related breathing disorder in a community sample of white and Hispanic children: the Tucson Children's Assessment of Sleep Apnea study. Author(s): Enright PL, Goodwin JL, Sherrill DL, Quan JR, Quan SF; Tucson Children's Assessment of Sleep Apnea study. Source: Archives of Pediatrics & Adolescent Medicine. 2003 September; 157(9): 901-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12963596&dopt=Abstract

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Blood pressure variability in obstructive sleep apnea: role of sympathetic nervous activity and effect of continuous positive airway pressure. Author(s): Bao X, Nelesen RA, Loredo JS, Dimsdale JE, Ziegler MG. Source: Blood Pressure Monitoring. 2002 December; 7(6): 301-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12488649&dopt=Abstract

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Blood transfusion in anemic infants with apnea of prematurity. Author(s): Westkamp E, Soditt V, Adrian S, Bohnhorst B, Groneck P, Poets CF. Source: Biology of the Neonate. 2002; 82(4): 228-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12381929&dopt=Abstract

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Blood viscosity and platelet function in patients with obstructive sleep apnea syndrome treated with nasal continuous positive airway pressure. Author(s): Reinhart WH, Oswald J, Walter R, Kuhn M. Source: Clinical Hemorheology and Microcirculation. 2002; 27(3-4): 201-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12454377&dopt=Abstract

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Body fat distribution, serum leptin, and cardiovascular risk factors in men with obstructive sleep apnea. Author(s): Schafer H, Pauleit D, Sudhop T, Gouni-Berthold I, Ewig S, Berthold HK. Source: Chest. 2002 September; 122(3): 829-39. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12226021&dopt=Abstract

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Body position and obstructive sleep apnea in children. Author(s): Fernandes do Prado LB, Li X, Thompson R, Marcus CL. Source: Sleep. 2002 February 1; 25(1): 66-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11833863&dopt=Abstract

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Brain morphology associated with obstructive sleep apnea. Author(s): Macey PM, Henderson LA, Macey KE, Alger JR, Frysinger RC, Woo MA, Harper RK, Yan-Go FL, Harper RM. Source: American Journal of Respiratory and Critical Care Medicine. 2002 November 15; 166(10): 1382-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12421746&dopt=Abstract

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Breath-hold training of humans reduces oxidative stress and blood acidosis after static and dynamic apnea. Author(s): Joulia F, Steinberg JG, Faucher M, Jamin T, Ulmer C, Kipson N, Jammes Y. Source: Respiratory Physiology & Neurobiology. 2003 August 14; 137(1): 19-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12871674&dopt=Abstract

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Butyrylcholinesterase (BCHE) genotyping for post-succinylcholine apnea in an Australian population. Author(s): Yen T, Nightingale BN, Burns JC, Sullivan DR, Stewart PM. Source: Clinical Chemistry. 2003 August; 49(8): 1297-308. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12881446&dopt=Abstract

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Can continuous positive airway pressure therapy improve the general health status of patients with obstructive sleep apnea?: a clinical effectiveness study. Author(s): Sin DD, Mayers I, Man GC, Ghahary A, Pawluk L. Source: Chest. 2002 November; 122(5): 1679-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12426271&dopt=Abstract

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Cardiorespiratory effects of added dead space in patients with heart failure and central sleep apnea. Author(s): Khayat RN, Xie A, Patel AK, Kaminski A, Skatrud JB. Source: Chest. 2003 May; 123(5): 1551-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12740273&dopt=Abstract

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Cardiovascular consequences of obstructive sleep apnea. Author(s): Wolk R, Somers VK. Source: Clinics in Chest Medicine. 2003 June; 24(2): 195-205. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12800778&dopt=Abstract

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Cardiovascular effects of continuous positive airway pressure in patients with heart failure and obstructive sleep apnea. Author(s): Kaneko Y, Floras JS, Usui K, Plante J, Tkacova R, Kubo T, Ando S, Bradley TD. Source: The New England Journal of Medicine. 2003 March 27; 348(13): 1233-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12660387&dopt=Abstract

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Case study: left eyelid swelling and apnea in a neonate. Author(s): Grubbs CA, Allen CH. Source: Seminars in Pediatric Infectious Diseases. 2003 January; 14(1): 5, 64-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12748915&dopt=Abstract

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Cephalometric analysis in obese and nonobese patients with obstructive sleep apnea syndrome. Author(s): Yu X, Fujimoto K, Urushibata K, Matsuzawa Y, Kubo K. Source: Chest. 2003 July; 124(1): 212-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12853525&dopt=Abstract

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Cephalometric evaluation of craniofacial and upper airway structures in Japanese patients with obstructive sleep apnea. Author(s): Endo S, Mataki S, Kurosaki N. Source: J Med Dent Sci. 2003 March; 50(1): 109-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12715927&dopt=Abstract

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Changes in depressive symptoms after continuous positive airway pressure treatment for obstructive sleep apnea. Author(s): Means MK, Lichstein KL, Edinger JD, Taylor DJ, Durrence HH, Husain AM, Aguillard RN, Radtke RA. Source: Sleep & Breathing = Schlaf & Atmung. 2003 March; 7(1): 31-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12712395&dopt=Abstract

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Clinical effects of locally delivered nicotine in obstructive sleep apnea syndrome. Author(s): Zevin S, Swed E, Cahan C. Source: American Journal of Therapeutics. 2003 May-June; 10(3): 170-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12756424&dopt=Abstract

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Clinical outcomes related to interface type in patients with obstructive sleep apnea/hypopnea syndrome who are using continuous positive airway pressure. Author(s): Massie CA, Hart RW. Source: Chest. 2003 April; 123(4): 1112-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12684301&dopt=Abstract

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Cognitive dysfunction in patients with obstructive sleep apnea (OSA): partial reversibility after continuous positive airway pressure (CPAP). Author(s): Ferini-Strambi L, Baietto C, Di Gioia MR, Castaldi P, Castronovo C, Zucconi M, Cappa SF. Source: Brain Research Bulletin. 2003 June 30; 61(1): 87-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12788211&dopt=Abstract

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Collateral damage: the effects of obstructive sleep apnea on bed partners. Author(s): Ashtyani H, Hutter DA. Source: Chest. 2003 September; 124(3): 780-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12969996&dopt=Abstract

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Comparison of surgery and nasal continuous positive airway pressure treatment for obstructive sleep apnea syndrome. Author(s): Hattori C, Nishimura T, Kawakatsu K, Hayakawa M, Suzuki K. Source: Acta Otolaryngol Suppl. 2003; (550): 46-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12737342&dopt=Abstract

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Con: sleep apnea is not an anatomic disorder. Author(s): Strohl KP. Source: American Journal of Respiratory and Critical Care Medicine. 2003 August 1; 168(3): 271-2; Discussion 272-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12888607&dopt=Abstract

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Concomitant impairment of growth hormone secretion and peripheral sensitivity in obese patients with obstructive sleep apnea syndrome. Author(s): Gianotti L, Pivetti S, Lanfranco F, Tassone F, Navone F, Vittori E, Rossetto R, Gauna C, Destefanis S, Grottoli S, De Giorgi R, Gai V, Ghigo E, Maccario M. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 November; 87(11): 5052-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12414871&dopt=Abstract

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Congenital myasthenic syndrome with episodic apnea in patients homozygous for a CHAT missense mutation. Author(s): Kraner S, Laufenberg I, Strassburg HM, Sieb JP, Steinlein OK. Source: Archives of Neurology. 2003 May; 60(5): 761-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12756141&dopt=Abstract

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Continuous positive airway pressure therapy for treating sleepiness in a diverse population with obstructive sleep apnea: results of a meta-analysis. Author(s): Patel SR, White DP, Malhotra A, Stanchina ML, Ayas NT. Source: Archives of Internal Medicine. 2003 March 10; 163(5): 565-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12622603&dopt=Abstract

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Contributions of upper airway mechanics and control mechanisms to severity of obstructive apnea. Author(s): Younes M. Source: American Journal of Respiratory and Critical Care Medicine. 2003 September 15; 168(6): 645-58. Epub 2003 May 28. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12773321&dopt=Abstract

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Correction of AV-nodal block in a 27-year-old man with severe obstructive sleep apnea--a case report. Author(s): Voigt L, Saul BI, Lombardo G, Reddy CV, Kassotis J. Source: Angiology. 2003 May-June; 54(3): 363-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12785031&dopt=Abstract

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Cycling sleep apnea: the balance of compensated and decompensated breathing. Author(s): Naughton MT. Source: American Journal of Respiratory and Critical Care Medicine. 2003 September 15; 168(6): 624-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12963578&dopt=Abstract

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Decreased pituitary-gonadal secretion in men with obstructive sleep apnea. Author(s): Luboshitzky R, Aviv A, Hefetz A, Herer P, Shen-Orr Z, Lavie L, Lavie P. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 July; 87(7): 3394-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12107256&dopt=Abstract

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Dental and skeletal changes after 4 years of obstructive sleep apnea treatment with a mandibular advancement device: a prospective, randomized study. Author(s): Ringqvist M, Walker-Engstrom ML, Tegelberg A, Ringqvist I. Source: American Journal of Orthodontics and Dentofacial Orthopedics : Official Publication of the American Association of Orthodontists, Its Constituent Societies, and the American Board of Orthodontics. 2003 July; 124(1): 53-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12867898&dopt=Abstract

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Dental devices; classification for intraoral devices for snoring and/or obstructive sleep apnea. Final rule. Author(s): Food and Drug Administration, HHS. Source: Federal Register. 2002 November 12; 67(218): 68510-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12428642&dopt=Abstract

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Detection of obstructive apnea events in sleeping infants from thoracoabdominal movements. Author(s): Groote AD, Groswasser J, Bersini H, Mathys P, Kahn A. Source: Journal of Sleep Research. 2002 June; 11(2): 161-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12028481&dopt=Abstract

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Determinants of chronic hypercapnia in Japanese men with obstructive sleep apnea syndrome. Author(s): Akashiba T, Kawahara S, Kosaka N, Ito D, Saito O, Majima T, Horie T. Source: Chest. 2002 February; 121(2): 415-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11834651&dopt=Abstract

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Determinants of daytime hypercapnia in obstructive sleep apnea: is obesity the only one to blame? Author(s): Gozal D. Source: Chest. 2002 February; 121(2): 320-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11834635&dopt=Abstract

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Determining the site of airway obstruction in obstructive sleep apnea with airway pressure measurements during sleep. Author(s): Demin H, Jingying Y, Jun W, Qingwen Y, Yuhua L, Jiangyong W. Source: The Laryngoscope. 2002 November; 112(11): 2081-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12439185&dopt=Abstract

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Diagnosis and treatment of obstructive sleep apnea in a stroke rehabilitation unit: a feasibility study. Author(s): Disler P, Hansford A, Skelton J, Wright P, Kerr J, O'Reilly J, Hepworth J, Middleton S, Sullivan C. Source: American Journal of Physical Medicine & Rehabilitation / Association of Academic Physiatrists. 2002 August; 81(8): 622-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12172072&dopt=Abstract

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Diagnosis of sleep apnea by automatic analysis of nasal pressure and forced oscillation impedance. Author(s): Steltner H, Staats R, Timmer J, Vogel M, Guttmann J, Matthys H, Christian Virchow J. Source: American Journal of Respiratory and Critical Care Medicine. 2002 April 1; 165(7): 940-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11934718&dopt=Abstract

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Diagnosis of sleep apnea. Author(s): Stevenson JE. Source: Wmj. 2003; 102(1): 25-7, 46. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12679967&dopt=Abstract

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Diastolic blood pressure is the first to rise in association with early subclinical obstructive sleep apnea: lessons from periodic examination screening. Author(s): Sharabi Y, Scope A, Chorney N, Grotto I, Dagan Y. Source: American Journal of Hypertension : Journal of the American Society of Hypertension. 2003 March; 16(3): 236-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12620704&dopt=Abstract

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Differential fMRI-BOLD signal response to apnea in humans and anesthetized rats. Author(s): Kannurpatti SS, Biswal BB, Hudetz AG. Source: Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine. 2002 May; 47(5): 864-70. Erratum In: Magn Reson Med 2002 July; 48(1): 214. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11979564&dopt=Abstract

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Difficult endotracheal intubation in patients with sleep apnea syndrome. Author(s): Siyam MA, Benhamou D. Source: Anesthesia and Analgesia. 2002 October; 95(4): 1098-102, Table of Contents. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12351303&dopt=Abstract

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Discriminative power of phrenic twitch-induced dynamic response for diagnosis of sleep apnea during wakefulness. Author(s): Verin E, Similowski T, Teixeira A, Series F. Source: Journal of Applied Physiology (Bethesda, Md. : 1985). 2003 January; 94(1): 31-7. Epub 2002 September 06. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12391097&dopt=Abstract

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Diurnal hypercapnia in patients with obstructive sleep apnea syndrome. Author(s): Golpe R, Jimenez A, Carpizo R. Source: Chest. 2002 September; 122(3): 1100-1; Author Reply 1101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12226064&dopt=Abstract

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Diurnal variation in daytime sleepiness of patients with sleep apnea syndrome. Author(s): Miyamoto M, Miyamoto T, Iwata K, Hirata K. Source: Psychiatry and Clinical Neurosciences. 2002 June; 56(3): 319-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12047614&dopt=Abstract

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Diving response and arterial oxygen saturation during apnea and exercise in breathhold divers. Author(s): Andersson JP, Liner MH, Runow E, Schagatay EK. Source: Journal of Applied Physiology (Bethesda, Md. : 1985). 2002 September; 93(3): 882-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12183481&dopt=Abstract

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Do the oscillations of cardiovascular parameters persist during voluntary apnea in humans? Author(s): Javorka M, Zila I, Javorka K, Calkovska A. Source: Physiological Research / Academia Scientiarum Bohemoslovaca. 2002; 51(3): 227-38. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12234114&dopt=Abstract

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Doppler measurement of blood flow velocities in extraocular orbital vessels in patients with obstructive sleep apnea syndrome. Author(s): Erdem CZ, Altin R, Erdem LO, Kargi S, Kart L, Cinar F, Ayoglu F. Source: Journal of Clinical Ultrasound : Jcu. 2003 June; 31(5): 250-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12767020&dopt=Abstract

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Dynamics of heart rate and sleep stages in normals and patients with sleep apnea. Author(s): Penzel T, Kantelhardt JW, Lo CC, Voigt K, Vogelmeier C. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2003 July; 28 Suppl 1: S48-53. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12827144&dopt=Abstract

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Effect of nasal continuous positive airway pressure treatment on blood pressure in patients with obstructive sleep apnea. Author(s): Becker HF, Jerrentrup A, Ploch T, Grote L, Penzel T, Sullivan CE, Peter JH. Source: Circulation. 2003 January 7; 107(1): 68-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12515745&dopt=Abstract

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Effect of nasal valve dilation on effective CPAP level in obstructive sleep apnea. Author(s): Schonhofer B, Kerl J, Suchi S, Kohler D, Franklin KA. Source: Respiratory Medicine. 2003 September; 97(9): 1001-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14509553&dopt=Abstract

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Effect of oral appliance therapy on upper airway collapsibility in obstructive sleep apnea. Author(s): Ng AT, Gotsopoulos H, Qian J, Cistulli PA. Source: American Journal of Respiratory and Critical Care Medicine. 2003 July 15; 168(2): 238-41. Epub 2003 April 30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12724125&dopt=Abstract

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Effect of the definition of hypopnea on apnea/hypopnea index. Author(s): Nigro CA, Rhodius EE. Source: Medicina (B Aires). 2003; 63(2): 119-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12793079&dopt=Abstract

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Effect of vertical dimension on efficacy of oral appliance therapy in obstructive sleep apnea. Author(s): Pitsis AJ, Darendeliler MA, Gotsopoulos H, Petocz P, Cistulli PA. Source: American Journal of Respiratory and Critical Care Medicine. 2002 September 15; 166(6): 860-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12231498&dopt=Abstract

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Effects of apnea on motor and cardiac rhythms. Author(s): Dosseville F, LaRue J. Source: Autonomic Neuroscience : Basic & Clinical. 2002 August 30; 99(2): 134-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12241088&dopt=Abstract

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Effects of mandibular posture on obstructive sleep apnea severity and the temporomandibular joint in patients fitted with an oral appliance. Author(s): de Almeida FR, Bittencourt LR, de Almeida CI, Tsuiki S, Lowe AA, Tufik S. Source: Sleep. 2002 August 1; 25(5): 507-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12150316&dopt=Abstract

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Effects of obstructive sleep apnea on circulating ICAM-1, IL-8, and MCP-1. Author(s): Ohga E, Tomita T, Wada H, Yamamoto H, Nagase T, Ouchi Y. Source: Journal of Applied Physiology (Bethesda, Md. : 1985). 2003 January; 94(1): 17984. Epub 2002 September 27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12391099&dopt=Abstract

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Effects of obstructive sleep apnea syndrome on serum aminotransferase levels in obese patients. Author(s): Chin K, Nakamura T, Takahashi K, Sumi K, Ogawa Y, Masuzaki H, Muro S, Hattori N, Matsumoto H, Niimi A, Chiba T, Nakao K, Mishima M, Ohi M, Nakamura T. Source: The American Journal of Medicine. 2003 April 1; 114(5): 370-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12714126&dopt=Abstract

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Elevated levels of C-reactive protein and interleukin-6 in patients with obstructive sleep apnea syndrome are decreased by nasal continuous positive airway pressure. Author(s): Yokoe T, Minoguchi K, Matsuo H, Oda N, Minoguchi H, Yoshino G, Hirano T, Adachi M. Source: Circulation. 2003 March 4; 107(8): 1129-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12615790&dopt=Abstract

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Endoscopic classification of pharyngeal stenosis pattern in obstructive sleep apnea hypopnea syndrome. Author(s): Higami S, Inoue Y, Higami Y, Takeuchi H, Ikoma H. Source: Psychiatry and Clinical Neurosciences. 2002 June; 56(3): 317-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12047613&dopt=Abstract

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Endoscopic examination of obstructive sleep apnea syndrome patients during druginduced sleep. Author(s): Iwanaga K, Hasegawa K, Shibata N, Kawakatsu K, Akita Y, Suzuki K, Yagisawa M, Nishimura T. Source: Acta Otolaryngol Suppl. 2003; (550): 36-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12737340&dopt=Abstract

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Enhanced ventilatory response to exercise in patients with chronic heart failure and central sleep apnea. Author(s): Arzt M, Harth M, Luchner A, Muders F, Holmer SR, Blumberg FC, Riegger GA, Pfeifer M. Source: Circulation. 2003 April 22; 107(15): 1998-2003. Epub 2003 Apr 14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12695297&dopt=Abstract

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Enuresis in children with sleep apnea. Author(s): Brooks LJ, Topol HI. Source: The Journal of Pediatrics. 2003 May; 142(5): 515-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12756383&dopt=Abstract

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Esophageal foreign bodies causing obstructive sleep apnea in a patient with SturgeWeber syndrome. Author(s): Watson NF, Kapur V. Source: Chest. 2003 July; 124(1): 400-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12853553&dopt=Abstract

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Evaluating mental fatigue in patients with obstructive sleep apnea syndrome by the Maastricht Questionnaire. Author(s): Hayakawa T, Fujita O, Ishida K, Usami T, Sugiura S, Kayukawa Y, Terashima M, Ohta T, Okada T. Source: Psychiatry and Clinical Neurosciences. 2002 June; 56(3): 313-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12047611&dopt=Abstract

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Evaluation of the POLYMESAM system in the diagnosis of obstructive sleep apnea syndrome. Author(s): Marrone O, Salvaggio A, Insalaco G, Bonsignore MR, Bonsignore G. Source: Monaldi Arch Chest Dis. 2001 December; 56(6): 486-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11980277&dopt=Abstract

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Evaluation of unattended automated titration to determine therapeutic continuous positive airway pressure in patients with obstructive sleep apnea. Author(s): Kessler R, Weitzenblum E, Chaouat A, Iamandi C, Alliotte T. Source: Chest. 2003 March; 123(3): 704-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12628866&dopt=Abstract

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Evidence of a sleep-specific blunted cortical response to inspiratory occlusions in mild obstructive sleep apnea syndrome. Author(s): Gora J, Trinder J, Pierce R, Colrain IM. Source: American Journal of Respiratory and Critical Care Medicine. 2002 November 1; 166(9): 1225-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12403692&dopt=Abstract

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Evidence-based medicine in sleep apnea surgery. Author(s): McMains KC, Terris DJ. Source: Otolaryngologic Clinics of North America. 2003 June; 36(3): 539-61, Viii. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12956101&dopt=Abstract

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Factors that affect swallowing-related apnea times in humans. Author(s): Miyazaki H, Yamashita H, Komiyama S. Source: European Archives of Oto-Rhino-Laryngology : Official Journal of the European Federation of Oto-Rhino-Laryngological Societies (Eufos) : Affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery. 1994; 251 Suppl 1: S104-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11894766&dopt=Abstract

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Falling asleep while driving and automobile accidents among patients with obstructive sleep apnea-hypopnea syndrome. Author(s): Shiomi T, Arita AT, Sasanabe R, Banno K, Yamakawa H, Hasegawa R, Ozeki K, Okada M, Ito A. Source: Psychiatry and Clinical Neurosciences. 2002 June; 56(3): 333-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12047620&dopt=Abstract

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Familial predisposition and cosegregation analysis of adult obstructive sleep apnea and the sudden infant death syndrome. Author(s): Gislason T, Johannsson JH, Haraldsson A, Olafsdottir BR, Jonsdottir H, Kong A, Frigge ML, Jonsdottir GM, Hakonarson H, Gulcher J, Stefansson K. Source: American Journal of Respiratory and Critical Care Medicine. 2002 September 15; 166(6): 833-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12231493&dopt=Abstract

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Fatigue in obstructive sleep apnea: driven by depressive symptoms instead of apnea severity? Author(s): Bardwell WA, Moore P, Ancoli-Israel S, Dimsdale JE. Source: The American Journal of Psychiatry. 2003 February; 160(2): 350-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12562583&dopt=Abstract

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Feasibility of using unattended polysomnography in children for research--report of the Tucson Children's Assessment of Sleep Apnea study (TuCASA). Author(s): Goodwin JL, Enright PL, Kaemingk KL, Rosen GM, Morgan WJ, Fregosi RF, Quan SF. Source: Sleep. 2001 December 15; 24(8): 937-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11766164&dopt=Abstract

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Feasibility study of Flextube reflectometry for localisation of upper airway obstruction in obstructive sleep apnea. Author(s): Hessel NS, Laman M, van Ammers VC, van Duijn H, de Vries N. Source: Rhinology. 2003 June; 41(2): 87-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12868373&dopt=Abstract

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Fetal hemoglobin synthesis determined by gamma-mRNA/gamma-mRNA + betamRNA quantitation in infants at risk for sudden infant death syndrome being monitored at home for apnea. Author(s): Bard H, Cote A, Praud JP, Infante-Rivard C, Gagnon C. Source: Pediatrics. 2003 October; 112(4): E285. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14523213&dopt=Abstract

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Fluticasone for obstructive sleep apnea. Author(s): Wheeler AJ, van Someren V. Source: The Journal of Pediatrics. 2002 April; 140(4): 489; Author Reply 489-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12006973&dopt=Abstract

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fMRI responses to cold pressor challenges in control and obstructive sleep apnea subjects. Author(s): Harper RM, Macey PM, Henderson LA, Woo MA, Macey KE, Frysinger RC, Alger JR, Nguyen KP, Yan-Go FL. Source: Journal of Applied Physiology (Bethesda, Md. : 1985). 2003 April; 94(4): 1583-95. Epub 2003 January 03. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12514164&dopt=Abstract

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Follow-up and outcomes of nasal CPAP therapy in patients with sleep apnea syndrome. Author(s): McNicholas WT. Source: Monaldi Arch Chest Dis. 2001 December; 56(6): 535-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11980286&dopt=Abstract

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Frequency of snoring and symptoms of sleep apnea among Pakistani medical students. Author(s): Pasha SN, Khan UA. Source: J Ayub Med Coll Abbottabad. 2003 January-March; 15(1): 23-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12870311&dopt=Abstract

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From epidemiology to physiology and pathology: apnea and arousal deficient theories in sudden infant death syndrome (SIDS)--with particular reference to hypoxic brainstem gliosis. Author(s): Sawaguchi T, Franco P, Kato I, Shimizu S, Kadhim H, Groswasser J, Sottiaux M, Togari H, Kobayashi M, Takashima S, Nishida H, Sawaguchi A, Kahn A. Source: Forensic Science International. 2002 September 14; 130 Suppl: S21-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12350297&dopt=Abstract

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Gastric bypass is an effective treatment for obstructive sleep apnea in patients with clinically significant obesity. Author(s): Rasheid S, Banasiak M, Gallagher SF, Lipska A, Kaba S, Ventimiglia D, Anderson WM, Murr MM. Source: Obesity Surgery : the Official Journal of the American Society for Bariatric Surgery and of the Obesity Surgery Society of Australia and New Zealand. 2003 February; 13(1): 58-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12630614&dopt=Abstract

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Gastroesophageal reflux and apnea of prematurity: no temporal relationship. Author(s): Peter CS, Sprodowski N, Bohnhorst B, Silny J, Poets CF. Source: Pediatrics. 2002 January; 109(1): 8-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11773535&dopt=Abstract

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Gastroesophageal reflux and obstructive sleep apnea. Author(s): Senior BA, Khan M, Schwimmer C, Rosenthal L, Benninger M. Source: The Laryngoscope. 2001 December; 111(12): 2144-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11802013&dopt=Abstract

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Gastroesophageal reflux common in patients with sleep apnea rather than snorers without sleep apnea. Author(s): Teramoto S, Yamamoto H, Ouchi Y. Source: Chest. 2003 August; 124(2): 767; Author Reply 767-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12907575&dopt=Abstract

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Gender and obstructive sleep apnea syndrome, part 1: Clinical features. Author(s): Kapsimalis F, Kryger MH. Source: Sleep. 2002 June 15; 25(4): 412-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12071542&dopt=Abstract

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Gender and obstructive sleep apnea syndrome, part 2: mechanisms. Author(s): Kapsimalis F, Kryger MH. Source: Sleep. 2002 August 1; 25(5): 499-506. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12150315&dopt=Abstract

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Gender differences in sleep apnea: the role of neck circumference. Author(s): Dancey DR, Hanly PJ, Soong C, Lee B, Shepard J Jr, Hoffstein V. Source: Chest. 2003 May; 123(5): 1544-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12740272&dopt=Abstract

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Gender differences in symptoms related to sleep apnea in a general population and in relation to referral to sleep clinic. Author(s): Larsson LG, Lindberg A, Franklin KA, Lundback B. Source: Chest. 2003 July; 124(1): 204-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12853524&dopt=Abstract

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Genetics of the apnea hypopnea index in Caucasians and African Americans: I. Segregation analysis. Author(s): Buxbaum SG, Elston RC, Tishler PV, Redline S. Source: Genetic Epidemiology. 2002 March; 22(3): 243-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11921084&dopt=Abstract

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Genioglossal advancement--a simple surgical procedure for sleep apnea. Case report and literature review. Author(s): Nagler RM, Laufer D. Source: European Surgical Research. Europaische Chirurgische Forschung. Recherches Chirurgicales Europeennes. 2002 September-October; 34(5): 373-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12364822&dopt=Abstract

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Genioglossus activity in children with obstructive sleep apnea during wakefulness and sleep onset. Author(s): Katz ES, White DP. Source: American Journal of Respiratory and Critical Care Medicine. 2003 September 15; 168(6): 664-70. Epub 2003 July 11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12857721&dopt=Abstract

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Genomic approaches to understanding obstructive sleep apnea. Author(s): Palmer LJ, Redline S. Source: Respiratory Physiology & Neurobiology. 2003 May 30; 135(2-3): 187-205. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12809619&dopt=Abstract

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Growth and biochemical markers of growth in children with snoring and obstructive sleep apnea. Author(s): Nieminen P, Lopponen T, Tolonen U, Lanning P, Knip M, Lopponen H. Source: Pediatrics. 2002 April; 109(4): E55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11927728&dopt=Abstract

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Health care services utilization in children with obstructive sleep apnea syndrome. Author(s): Reuveni H, Simon T, Tal A, Elhayany A, Tarasiuk A. Source: Pediatrics. 2002 July; 110(1 Pt 1): 68-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12093948&dopt=Abstract

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Heart failure and sleep apnea: emphasis on practical therapeutic options. Author(s): Javaheri S. Source: Clinics in Chest Medicine. 2003 June; 24(2): 207-22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12800779&dopt=Abstract

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Heated humidification during nasal continuous positive airway pressure for obstructive sleep apnea syndrome: objective evaluation of efficacy with nasal peak inspiratory flow measurements. Author(s): Winck JC, Delgado JL, Almeida JM, Marques JA. Source: American Journal of Rhinology. 2002 May-June; 16(3): 175-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12141777&dopt=Abstract

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High leg motor activity in sleep apnea hypopnea patients: efficacy of clonazepam combined with nasal CPAP on polysomnographic variables. Author(s): Noseda A, Nouvelle M, Lanquart JR, Kempenaers Ch, De Maertelaer V, Linkowski R, Kerkhofs M. Source: Respiratory Medicine. 2002 September; 96(9): 693-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12243315&dopt=Abstract

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Higher prevalence of smoking in patients diagnosed as having obstructive sleep apnea. Author(s): Kashyap R, Hock LM, Bowman TJ. Source: Sleep & Breathing = Schlaf & Atmung. 2001 December; 5(4): 167-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11868156&dopt=Abstract

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High-flow nasal cannula versus nasal continuous positive airway pressure in the management of apnea of prematurity. Author(s): Dutta S. Source: Pediatrics. 2002 April; 109(4): 718-9; Author Reply 718-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11927724&dopt=Abstract

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Histopathology of the uvula and the soft palate in patients with mild, moderate, and severe obstructive sleep apnea. Author(s): Berger G, Gilbey P, Hammel I, Ophir D. Source: The Laryngoscope. 2002 February; 112(2): 357-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11889397&dopt=Abstract

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Home apnea monitoring for infants. A discussion of primary care issues. Author(s): Bennett AD. Source: Adv Nurse Pract. 2002 March; 10(3): 48-53; Quiz 53-4. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12418336&dopt=Abstract

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Home sleep studies in the assessment of sleep apnea/hypopnea syndrome. Author(s): Golpe R, Jimenez A, Carpizo R. Source: Chest. 2002 October; 122(4): 1156-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12377836&dopt=Abstract

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Home unattended vs hospital telemonitored polysomnography in suspected obstructive sleep apnea syndrome: a randomized crossover trial. Author(s): Gagnadoux F, Pelletier-Fleury N, Philippe C, Rakotonanahary D, Fleury B. Source: Chest. 2002 March; 121(3): 753-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11888956&dopt=Abstract

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How, what, and why of sleep apnea. Perspectives for primary care physicians. Author(s): Chung SA, Jairam S, Hussain MR, Shapiro CM. Source: Can Fam Physician. 2002 June; 48: 1073-80. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12113194&dopt=Abstract

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Hyoid myotomy with suspension under local anesthesia for obstructive sleep apnea syndrome. Author(s): Neruntarat C. Source: Eur Arch Otorhinolaryngol. 2003 May;260(5):286-90. Epub 2002 December 05. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12750922&dopt=Abstract

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Hypercapnia and ventilatory periodicity in obstructive sleep apnea syndrome. Author(s): Ayappa I, Berger KI, Norman RG, Oppenheimer BW, Rapoport DM, Goldring RM. Source: American Journal of Respiratory and Critical Care Medicine. 2002 October 15; 166(8): 1112-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12379556&dopt=Abstract

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I have congested heart failure and I was recently diagnosed with sleep apnea. Are the two connected? Author(s): Francis GS. Source: Heart Advis. 2002 October; 5(10): 8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12420699&dopt=Abstract

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Identifying sleep apnea. Author(s): Schotland H. Source: Chest. 2003 February; 123(2): 656. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12576402&dopt=Abstract

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Impact of sleep apnea on sympathetic nervous system activity in heart failure. Author(s): Solin P, Kaye DM, Little PJ, Bergin P, Richardson M, Naughton MT. Source: Chest. 2003 April; 123(4): 1119-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12684302&dopt=Abstract

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Impaired vasodilator responses in obstructive sleep apnea are improved with continuous positive airway pressure therapy. Author(s): Imadojemu VA, Gleeson K, Quraishi SA, Kunselman AR, Sinoway LI, Leuenberger UA. Source: American Journal of Respiratory and Critical Care Medicine. 2002 April 1; 165(7): 950-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11934720&dopt=Abstract

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In vivo platelet activation is increased during sleep in patients with obstructive sleep apnea syndrome. Author(s): Geiser T, Buck F, Meyer BJ, Bassetti C, Haeberli A, Gugger M. Source: Respiration; International Review of Thoracic Diseases. 2002; 69(3): 229-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12097766&dopt=Abstract

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Incidence and severity of obstructive sleep apnea following pharyngeal flap surgery in patients with cleft palate. Author(s): Liao YF, Chuang ML, Chen PK, Chen NH, Yun C, Huang CS. Source: The Cleft Palate-Craniofacial Journal : Official Publication of the American Cleft Palate-Craniofacial Association. 2002 May; 39(3): 312-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12019007&dopt=Abstract

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Incidence of sleep apnea in a presumably healthy working population: a significant relationship with excessive daytime sleepiness. Author(s): Lavie P. Source: Sleep. 2002 June 15; 25(4): 312-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12071537&dopt=Abstract

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Increased 8-isoprostane and interleukin-6 in breath condensate of obstructive sleep apnea patients. Author(s): Carpagnano GE, Kharitonov SA, Resta O, Foschino-Barbaro MP, Gramiccioni E, Barnes PJ. Source: Chest. 2002 October; 122(4): 1162-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12377837&dopt=Abstract

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Increased C-reactive protein and increased plasma interleukin-6 may synergistically affect the progression of coronary atherosclerosis in obstructive sleep apnea syndrome. Author(s): Teramoto S, Yamamoto H, Ouchi Y. Source: Circulation. 2003 February 11; 107(5): E40-0. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12578892&dopt=Abstract

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Increased incidence of cardiovascular disease in middle-aged men with obstructive sleep apnea: a 7-year follow-up. Author(s): Peker Y, Hedner J, Norum J, Kraiczi H, Carlson J. Source: American Journal of Respiratory and Critical Care Medicine. 2002 July 15; 166(2): 159-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12119227&dopt=Abstract

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Increased physician-reported sleep apnea: the National Ambulatory Medical Care Survey. Author(s): Namen AM, Dunagan DP, Fleischer A, Tillett J, Barnett M, McCall WV, Haponik EF. Source: Chest. 2002 June; 121(6): 1741-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12065333&dopt=Abstract

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Indications for treatment of obstructive sleep apnea in adults. Author(s): Strollo PJ Jr. Source: Clinics in Chest Medicine. 2003 June; 24(2): 307-13, Vii. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12800786&dopt=Abstract

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Induction of sensory long-term facilitation in the carotid body by intermittent hypoxia: implications for recurrent apneas. Author(s): Peng YJ, Overholt JL, Kline D, Kumar GK, Prabhakar NR. Source: Proceedings of the National Academy of Sciences of the United States of America. 2003 August 19; 100(17): 10073-8. Epub 2003 Aug 07. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12907705&dopt=Abstract

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Influence of mandibular protruding device on airway passages and dentofacial characteristics in obstructive sleep apnea and snoring. Author(s): Fransson AM, Tegelberg A, Svenson BA, Lennartsson B, Isacsson G. Source: American Journal of Orthodontics and Dentofacial Orthopedics : Official Publication of the American Association of Orthodontists, Its Constituent Societies, and the American Board of Orthodontics. 2002 October; 122(4): 371-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12411882&dopt=Abstract

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Influence of sleep state on frequency of swallowing, apnea, and arousal in human infants. Author(s): Don GW, Waters KA. Source: Journal of Applied Physiology (Bethesda, Md. : 1985). 2003 June; 94(6): 2456-64. Epub 2003 February 07. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12576405&dopt=Abstract

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Insulin resistance, hyperleptinemia, and obstructive sleep apnea in LaunoisBensaude syndrome. Author(s): Harsch IA, Schahin SP, Fuchs FS, Hahn EG, Lohmann T, Konturek PC, Ficker JH. Source: Obesity Research. 2002 July; 10(7): 625-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12105284&dopt=Abstract

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Interaction between apnea, prone sleep position and gliosis in the brainstems of victims of SIDS. Author(s): Sawaguchi T, Franco P, Kato I, Shimizu S, Kadhim H, Groswasser J, Sottiaux M, Togari H, Kobayashi M, Nishida H, Sawaguchi A, Kahn A. Source: Forensic Science International. 2002 September 14; 130 Suppl: S44-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12350300&dopt=Abstract

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Intestinal malabsorption as a manifestation of obstructive sleep apnea. Author(s): Knox TA, Gazi T, Kastrinos F, White AC. Source: Digestive Diseases and Sciences. 2003 January; 48(1): 83-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12645794&dopt=Abstract

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Is chronic obstructive pulmonary disease related to sleep apnea-hypopnea syndrome? Author(s): Fleetham JA. Source: American Journal of Respiratory and Critical Care Medicine. 2003 January 1; 167(1): 3-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12502469&dopt=Abstract

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Is the relationship between obstructive sleep apnea and gastroesophageal reflux clinically important? Author(s): Field SK, Flemons WW. Source: Chest. 2002 June; 121(6): 1730-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12065328&dopt=Abstract

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Knowledge of sleep apnea in a sample grouping of primary care physicians. Author(s): Chung SA, Jairam S, Hussain MR, Shapiro CM. Source: Sleep & Breathing = Schlaf & Atmung. 2001 September; 5(3): 115-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11868150&dopt=Abstract

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Laryngomalacia causing sleep apnea in an osteogenesis imperfecta patient. Author(s): Li HY, Fang TJ, Lin JL, Lee ZL, Lee LA. Source: American Journal of Otolaryngology. 2002 November-December; 23(6): 378-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12430132&dopt=Abstract

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Laser midline glossectomy and lingual tonsillectomy as treatments for sleep apnea syndrome. Author(s): Yonekura A, Kawakatsu K, Suzuki K, Nishimura T. Source: Acta Otolaryngol Suppl. 2003; (550): 56-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12737344&dopt=Abstract

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Laser-assisted uvulopalatoplasty and tonsillectomy for the management of obstructive sleep apnea syndrome. Author(s): Kern RC, Kutler DI, Reid KJ, Conley DB, Herzon GD, Zee P. Source: The Laryngoscope. 2003 July; 113(7): 1175-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12838016&dopt=Abstract

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93

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Laser-assisted uvulopalatoplasty for the management of obstructive sleep apnea: myths and facts. Author(s): Finkelstein Y, Stein G, Ophir D, Berger R, Berger G. Source: Archives of Otolaryngology--Head & Neck Surgery. 2002 April; 128(4): 429-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11926920&dopt=Abstract

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Lateral position decreases collapsibility of the passive pharynx in patients with obstructive sleep apnea. Author(s): Isono S, Tanaka A, Nishino T. Source: Anesthesiology. 2002 October; 97(4): 780-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12357140&dopt=Abstract

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Learning, memory, and executive control in individuals with obstructive sleep apnea syndrome. Author(s): Salorio CF, White DA, Piccirillo J, Duntley SP, Uhles ML. Source: J Clin Exp Neuropsychol. 2002 February; 24(1): 93-100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11935427&dopt=Abstract

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Left ventricular dysfunction and sleep apnea syndrome: cause or consequence? Author(s): Bendjelid K. Source: Chest. 2003 May; 123(5): 1774; Author Reply 1774-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12740306&dopt=Abstract

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Left ventricular dysfunction, pulmonary hypertension, obesity, and sleep apnea. Author(s): Blankfield RP, Tapolyai AA, Zyzanski SJ. Source: Sleep & Breathing = Schlaf & Atmung. 2001 June; 5(2): 57-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11868142&dopt=Abstract

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Left ventricular hypertrophy and abnormal ventricular geometry in children and adolescents with obstructive sleep apnea. Author(s): Amin RS, Kimball TR, Bean JA, Jeffries JL, Willging JP, Cotton RT, Witt SA, Glascock BJ, Daniels SR. Source: American Journal of Respiratory and Critical Care Medicine. 2002 May 15; 165(10): 1395-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12016102&dopt=Abstract

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Left ventricular hypertrophy is a common echocardiographic abnormality in severe obstructive sleep apnea and reverses with nasal continuous positive airway pressure. Author(s): Cloward TV, Walker JM, Farney RJ, Anderson JL. Source: Chest. 2003 August; 124(2): 594-601. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12907548&dopt=Abstract

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Left ventricular systolic dysfunction in patients with obstructive sleep apnea syndrome. Author(s): Laaban JP, Pascal-Sebaoun S, Bloch E, Orvoen-Frija E, Oppert JM, Huchon G. Source: Chest. 2002 October; 122(4): 1133-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12377833&dopt=Abstract

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Lifestyle-related weight gain in obese men with newly diagnosed obstructive sleep apnea. Author(s): Traviss KA, Barr SI, Fleming JA, Ryan CF. Source: Journal of the American Dietetic Association. 2002 May; 102(5): 703-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12008998&dopt=Abstract

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Longitudinal follow-up of obstructive sleep apnea following Furlow palatoplasty in children with cleft palate: a preliminary report. Author(s): Liao YF, Yun C, Huang CS, Chen PK, Chen NH, Hung KF, Chuang ML. Source: The Cleft Palate-Craniofacial Journal : Official Publication of the American Cleft Palate-Craniofacial Association. 2003 May; 40(3): 269-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12733955&dopt=Abstract

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Long-term compliance rates to continuous positive airway pressure in obstructive sleep apnea: a population-based study. Author(s): Sin DD, Mayers I, Man GC, Pawluk L. Source: Chest. 2002 February; 121(2): 430-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11834653&dopt=Abstract

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Long-term surgical follow-up of sleep apnea syndrome. Author(s): Kawakatsu K, Nishimura T. Source: Acta Otolaryngol Suppl. 2003; (550): 11-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12737335&dopt=Abstract

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Management of sleep apnea. Author(s): Clemenson N. Source: The Journal of the American Board of Family Practice / American Board of Family Practice. 2002 September-October; 15(5): 433-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12350070&dopt=Abstract

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Mandibular advancement devices: rate of contraindications in 100 consecutive obstructive sleep apnea patients. Author(s): Petit FX, Pepin JL, Bettega G, Sadek H, Raphael B, Levy P. Source: American Journal of Respiratory and Critical Care Medicine. 2002 August 1; 166(3): 274-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12153957&dopt=Abstract

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Mandibular lengthening by distraction osteogenesis for treatment of obstructive sleep apnea syndrome: a case report. Author(s): Harada K, Higashinakagawa M, Omura K. Source: Cranio. 2003 January; 21(1): 61-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12555933&dopt=Abstract

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Marked improvement in nocturnal gastroesophageal reflux in a large cohort of patients with obstructive sleep apnea treated with continuous positive airway pressure. Author(s): Green BT, Broughton WA, O'Connor JB. Source: Archives of Internal Medicine. 2003 January 13; 163(1): 41-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12523915&dopt=Abstract

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Maxillomandibular advancement surgery for obstructive sleep apnea syndrome. Author(s): Prinsell JR. Source: The Journal of the American Dental Association. 2002 November; 133(11): 148997; Quiz 1539-40. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12462692&dopt=Abstract

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Measurement of sleep apnea during obesity treatment. Author(s): Billington CJ. Source: Obesity Research. 2002 November; 10 Suppl 1: 38S-41S. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12446857&dopt=Abstract

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Measurement properties of the calgary sleep apnea quality of life index. Author(s): Flemons WW, Reimer MA. Source: American Journal of Respiratory and Critical Care Medicine. 2002 January 15; 165(2): 159-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11790647&dopt=Abstract

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Medical devices; apnea monitor; special controls. Final rule. Author(s): Food and Drug Administration, HHS. Source: Federal Register. 2002 July 17; 67(137): 46851-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12125715&dopt=Abstract

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Metabolic correlates with obstructive sleep apnea in obese subjects. Author(s): de la Eva RC, Baur LA, Donaghue KC, Waters KA. Source: The Journal of Pediatrics. 2002 June; 140(6): 654-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12072866&dopt=Abstract

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Model-based assessment of autonomic control in obstructive sleep apnea syndrome during sleep. Author(s): Jo JA, Blasi A, Valladares E, Juarez R, Baydur A, Khoo MC. Source: American Journal of Respiratory and Critical Care Medicine. 2003 January 15; 167(2): 128-36. Epub 2002 October 03. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12406844&dopt=Abstract

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Model-based assessment of autonomic control in obstructive sleep apnea syndrome. Author(s): Belozeroff V, Berry RB, Khoo MC. Source: Sleep. 2003 February 1; 26(1): 65-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12627735&dopt=Abstract

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Modified maxillomandibular advancement for the treatment of obstructive sleep apnea: a preliminary report. Author(s): Goh YH, Lim KA. Source: The Laryngoscope. 2003 September; 113(9): 1577-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12972937&dopt=Abstract

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Monitoring functional residual capacity (FRC) by quantifying oxygen/carbon dioxide fluxes during a short apnea. Author(s): Stenqvist O, Olegard C, Sondergaard S, Odenstedt H, Karason S, Lundin S. Source: Acta Anaesthesiologica Scandinavica. 2002 July; 46(6): 732-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12059900&dopt=Abstract

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Morbidity of obstructive sleep apnea in children: facts and theory. Author(s): Gozal D. Source: Sleep & Breathing = Schlaf & Atmung. 2001; 5(1): 35-42. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11868138&dopt=Abstract

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More than a snore: recognizing the danger of sleep apnea. Author(s): Tate J, Tasota FJ. Source: Nursing. 2002 August; 32(8): 46-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12352851&dopt=Abstract

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Mortised genioplasty in the treatment of obstructive sleep apnea: an historical perspective and modification of design. Author(s): Hendler B, Silverstein K, Giannakopoulos H, Costello BJ. Source: Sleep & Breathing = Schlaf & Atmung. 2001 December; 5(4): 173-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11868157&dopt=Abstract

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MRI findings in the hypopharynx and the larynx of a patient with acromegaly associated with severe obstructive sleep apnea syndrome. Author(s): Hidaka H, Katakami H, Miyazono Y, Matsukura S. Source: Endocrine Journal. 1999 March; 46 Suppl: S105-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12054109&dopt=Abstract

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Multilevel temperature-controlled radiofrequency therapy of soft palate, base of tongue, and tonsils in adults with obstructive sleep apnea. Author(s): Fischer Y, Khan M, Mann WJ. Source: The Laryngoscope. 2003 October; 113(10): 1786-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14520107&dopt=Abstract

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Narcolepsy-like symptoms in a patient with down syndrome and without obstructive sleep apnea. Author(s): Dominguez-Ortega L, Salin-Pascual RJ, Diaz-Gallego E. Source: Sleep. 2003 May 1; 26(3): 285-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12749546&dopt=Abstract

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Nasal breathing and continuous positive airway pressure (CPAP) in patients with obstructive sleep apnea (OSA). Author(s): Hollandt JH, Mahlerwein M. Source: Sleep & Breathing = Schlaf & Atmung. 2003 June; 7(2): 87-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12861488&dopt=Abstract

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Nasal CPAP treatment for obstructive sleep apnea: developing a new perspective on dosing strategies and compliance. Author(s): Stepnowsky CJ Jr, Moore PJ. Source: Journal of Psychosomatic Research. 2003 June; 54(6): 599-605. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12781315&dopt=Abstract

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Nasal intermittent positive pressure ventilation (NIPPV) versus nasal continuous positive airway pressure (NCPAP) for apnea of prematurity. Author(s): Lemyre B, Davis PG, de Paoli AG. Source: Cochrane Database Syst Rev. 2002; (1): Cd002272. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11869635&dopt=Abstract

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Nasal resistances are useful in identifying children with severe obstructive sleep apnea before polysomnography. Author(s): Rizzi M, Onorato J, Andreoli A, Colombo S, Pecis M, Marchisio P, Morelli M, Principi N, Esposito S, Sergi M. Source: International Journal of Pediatric Otorhinolaryngology. 2002 August 1; 65(1): 713. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12127217&dopt=Abstract

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Neural responses during Valsalva maneuvers in obstructive sleep apnea syndrome. Author(s): Henderson LA, Woo MA, Macey PM, Macey KE, Frysinger RC, Alger JR, Yan-Go F, Harper RM. Source: Journal of Applied Physiology (Bethesda, Md. : 1985). 2003 March; 94(3): 106374. Epub 2002 November 01. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12433858&dopt=Abstract

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Neuropsychological changes and treatment compliance in older adults with sleep apnea. Author(s): Aloia MS, Ilniczky N, Di Dio P, Perlis ML, Greenblatt DW, Giles DE. Source: Journal of Psychosomatic Research. 2003 January; 54(1): 71-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12505557&dopt=Abstract

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Neuropsychological impairment and quality of life in obstructive sleep apnea. Author(s): Sateia MJ. Source: Clinics in Chest Medicine. 2003 June; 24(2): 249-59. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12800782&dopt=Abstract

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New desaturation index to evaluate neonatal apnea using polygraphy. Author(s): Minowa H, Uchida Y, Ebisu R, Yoshibayashi M, Takahashi Y, Yoshioka A. Source: Pediatrics International : Official Journal of the Japan Pediatric Society. 2003 June; 45(3): 294-300. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12828584&dopt=Abstract

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Night-to-night variability of polysomnography in children with suspected obstructive sleep apnea. Author(s): Katz ES, Greene MG, Carson KA, Galster P, Loughlin GM, Carroll J, Marcus CL. Source: The Journal of Pediatrics. 2002 May; 140(5): 589-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12032527&dopt=Abstract

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Nitric oxide (NO) and obstructive sleep apnea (OSA). Author(s): Haight JS, Djupesland PG. Source: Sleep & Breathing = Schlaf & Atmung. 2003 June; 7(2): 53-62. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12861485&dopt=Abstract

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Nocturia: a problem that disrupts sleep and predicts obstructive sleep apnea. Author(s): Chasens ER, Umlauf MG. Source: Geriatric Nursing (New York, N.Y.). 2003 March-April; 24(2): 76-81, 105. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12714959&dopt=Abstract

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Nocturnal gastroesophageal reflux: symptom of obstructive sleep apnea syndrome in association with impaired swallowing. Author(s): Teramoto S, Kume H, Ouchi Y. Source: Chest. 2002 December; 122(6): 2266-7; Author Reply 2267. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12475880&dopt=Abstract

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Nocturnal polyuria in type 2 diabetes: a symptom of obstructive sleep apnea. Author(s): Chasens ER, Umlauf MG, Pillion DJ, Wells JA. Source: Diabetes Educ. 2002 May-June; 28(3): 424-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12068651&dopt=Abstract

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Nocturnal problems in postpolio syndrome: sleep apnea symptoms and nocturia. Author(s): Chasens ER, Umlauf M, Valappil T, Singh KP. Source: Rehabilitation Nursing : the Official Journal of the Association of Rehabilitation Nurses. 2001 March-April; 26(2): 66-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12035702&dopt=Abstract

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Nonpharmacologic care of heart failure: counseling, dietary restriction, rehabilitation, treatment of sleep apnea, and ultrafiltration. Author(s): Colonna P, Sorino M, D'Agostino C, Bovenzi F, De Luca L, Arrigo F, de Luca I. Source: The American Journal of Cardiology. 2003 May 8; 91(9A): 41F-50F. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12729849&dopt=Abstract

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Normal-tension glaucoma is associated with sleep apnea syndrome. Author(s): Mojon DS, Hess CW, Goldblum D, Boehnke M, Koerner F, Gugger M, Bassetti C, Mathis J. Source: Ophthalmologica. Journal International D'ophtalmologie. International Journal of Ophthalmology. Zeitschrift Fur Augenheilkunde. 2002 May-June; 216(3): 180-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12065854&dopt=Abstract

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Obesity and obstructive sleep apnea syndrome. Author(s): Nishimura Y, Nishimura T, Hattori H, Hattori C, Yonekura A, Suzuki K. Source: Acta Otolaryngol Suppl. 2003; (550): 22-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12737336&dopt=Abstract

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Obstructive sleep apnea and cardiovascular disease. Author(s): Lattimore JD, Celermajer DS, Wilcox I. Source: Journal of the American College of Cardiology. 2003 May 7; 41(9): 1429-37. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12742277&dopt=Abstract

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Obstructive sleep apnea and dentists. Author(s): Schmidt-Nowara W. Source: Cranio. 2003 April; 21(2): 81-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12723851&dopt=Abstract

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Obstructive sleep apnea and the recurrence of atrial fibrillation. Author(s): Kanagala R, Murali NS, Friedman PA, Ammash NM, Gersh BJ, Ballman KV, Shamsuzzaman AS, Somers VK. Source: Circulation. 2003 May 27; 107(20): 2589-94. Epub 2003 May 12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12743002&dopt=Abstract

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Obstructive sleep apnea caused by bilateral vocal fold paralysis. Author(s): Aziz L, Ejnell H. Source: Ear, Nose, & Throat Journal. 2003 April; 82(4): 326-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12735166&dopt=Abstract

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Obstructive sleep apnea in a clinical series of adult epilepsy patients: frequency and features of the comorbidity. Author(s): Manni R, Terzaghi M, Arbasino C, Sartori I, Galimberti CA, Tartara A. Source: Epilepsia. 2003 June; 44(6): 836-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12790898&dopt=Abstract

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Obstructive sleep apnea in children: an update. Author(s): Sterni LM, Tunkel DE. Source: Pediatric Clinics of North America. 2003 April; 50(2): 427-43. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12809332&dopt=Abstract

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Obstructive sleep apnea in epilepsy. Author(s): Vaughn BV, D'Cruz OF. Source: Clinics in Chest Medicine. 2003 June; 24(2): 239-48. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12800781&dopt=Abstract

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Obstructive sleep apnea syndrome and snoring in patients with bilateral vocal cord paralysis. Author(s): Misiolek M, Namyslowski G, Karpe J, Ziora D, Misiolek H, Czecior E, Scierski W. Source: Eur Arch Otorhinolaryngol. 2003 April;260(4):183-5. Epub 2002 October 18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12709800&dopt=Abstract

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Obstructive sleep apnea syndrome in ambulatory surgical patients. Author(s): Mull Y, Bedder M. Source: Aorn Journal. 2002 September; 76(3): 458-64. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12227289&dopt=Abstract

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Obstructive sleep apnea syndrome in children. Author(s): Uruma Y, Suzuki K, Hattori H, Hattori C, Nishimura T. Source: Acta Otolaryngol Suppl. 2003; (550): 6-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12737334&dopt=Abstract

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Obstructive sleep apnea syndrome in children. Author(s): Schroeder BM; American Academy of Pediatrics. Source: American Family Physician. 2002 October 1; 66(7): 1338, 1343-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12387446&dopt=Abstract

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Obstructive sleep apnea syndrome, normal tension glaucoma, and nCPAP therapy--a short note. Author(s): Kremmer S, Niederdraing N, Ayertey HD, Steuhl KP, Selbach JM. Source: Sleep. 2003 March 15; 26(2): 161-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12683474&dopt=Abstract

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Obstructive sleep apnea syndrome. Author(s): Yantis MA. Source: The American Journal of Nursing. 2002 June; 102(6): 83, 85. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12394082&dopt=Abstract

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Obstructive sleep apnea. Author(s): Qureshi A, Ballard RD. Source: The Journal of Allergy and Clinical Immunology. 2003 October; 112(4): 643-51; Quiz 652. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14564340&dopt=Abstract

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Obstructive sleep apnea: implications for cardiac and vascular disease. Author(s): Shamsuzzaman AS, Gersh BJ, Somers VK. Source: Jama : the Journal of the American Medical Association. 2003 October 8; 290(14): 1906-14. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14532320&dopt=Abstract

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Occlusal and skeletal effects of an oral appliance in the treatment of obstructive sleep apnea. Author(s): Rose EC, Staats R, Virchow C Jr, Jonas IE. Source: Chest. 2002 September; 122(3): 871-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12226026&dopt=Abstract

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Occult supraglottic lymphatic malformation presenting as obstructive sleep apnea. Author(s): Chan J, Younes A, Koltai PJ. Source: International Journal of Pediatric Otorhinolaryngology. 2003 March; 67(3): 293-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12633931&dopt=Abstract

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Overnight home oximetry: can it identify patients with obstructive sleep apneahypopnea who have minimal daytime sleepiness? Author(s): Hussain SF, Fleetham JA. Source: Respiratory Medicine. 2003 May; 97(5): 537-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12735672&dopt=Abstract

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Parapharyngeal causes of sleep apnea syndrome: two case reports and review of the literature. Author(s): Desuter G, Castelein S, de Toeuf C, Rombaux P, Hamoir M. Source: Acta Otorhinolaryngol Belg. 2002; 56(2): 189-94. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12092329&dopt=Abstract

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Parapharyngeal lipoma causing obstructive sleep apnea syndrome. Author(s): Pellanda A, Zagury S, Pasche P. Source: Otolaryngology and Head and Neck Surgery. 2003 February; 128(2): 301-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12601335&dopt=Abstract

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Peripheral arterial tonometry for the diagnosis of obstructive sleep apnea. Author(s): Penzel T, Fricke R, Jerrentrup A, Peter JH, Vogelmeier C. Source: Biomed Tech (Berl). 2002; 47 Suppl 1 Pt 1: 315-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12451851&dopt=Abstract

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Phenotypic and functional characterization of blood gammadelta T cells in sleep apnea. Author(s): Dyugovskaya L, Lavie P, Lavie L. Source: American Journal of Respiratory and Critical Care Medicine. 2003 July 15; 168(2): 242-9. Epub 2003 April 30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12724124&dopt=Abstract

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Physical activity and perception of energy and fatigue in obstructive sleep apnea. Author(s): Hong S, Dimsdale JE. Source: Medicine and Science in Sports and Exercise. 2003 July; 35(7): 1088-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12840627&dopt=Abstract

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Plasma vascular endothelial growth factor in sleep apnea syndrome: effects of nasal continuous positive air pressure treatment. Author(s): Lavie L, Kraiczi H, Hefetz A, Ghandour H, Perelman A, Hedner J, Lavie P. Source: American Journal of Respiratory and Critical Care Medicine. 2002 June 15; 165(12): 1624-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12070063&dopt=Abstract

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Platelet activation in patients with obstructive sleep apnea syndrome and effects of nasal-continuous positive airway pressure. Author(s): Shimizu M, Kamio K, Haida M, Ono Y, Miyachi H, Yamamoto M, Shinohara Y, Ando Y. Source: Tokai J Exp Clin Med. 2002 December; 27(4): 107-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12713015&dopt=Abstract

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Possible contributing factors of sleep apnea syndrome to resistant hypertension. Author(s): Zelveian PA. Source: Sleep. 2003 February 1; 26(1): 12; Author Reply 12. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12627725&dopt=Abstract

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Postevent ventilation as a function of CO(2) load during respiratory events in obstructive sleep apnea. Author(s): Berger KI, Ayappa I, Sorkin IB, Norman RG, Rapoport DM, Goldring RM. Source: Journal of Applied Physiology (Bethesda, Md. : 1985). 2002 September; 93(3): 917-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12183486&dopt=Abstract

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Posture of patients with sleep apnea during sleep. Author(s): Akita Y, Kawakatsu K, Hattori C, Hattori H, Suzuki K, Nishimura T. Source: Acta Otolaryngol Suppl. 2003; (550): 41-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12737341&dopt=Abstract

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Predicting effective continuous positive airway pressure in Taiwanese patients with obstructive sleep apnea syndrome. Author(s): Lin IF, Chuang ML, Liao YF, Chen NH, Li HY. Source: J Formos Med Assoc. 2003 April; 102(4): 215-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12833183&dopt=Abstract

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Predicting sleep apnea and excessive day sleepiness in the severely obese: indicators for polysomnography. Author(s): Dixon JB, Schachter LM, O'Brien PE. Source: Chest. 2003 April; 123(4): 1134-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12684304&dopt=Abstract

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Prevalence and pathogenesis of sleep apnea and lung disease in acromegaly. Author(s): Fatti LM, Scacchi M, Pincelli AI, Lavezzi E, Cavagnini F. Source: Pituitary. 2001 September; 4(4): 259-62. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12501976&dopt=Abstract

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Prevalence and predictors of nocturia in obstructive sleep apnea-hypopnea syndrome-a retrospective study. Author(s): Hajduk IA, Strollo PJ Jr, Jasani RR, Atwood CW Jr, Houck PR, Sanders MH. Source: Sleep. 2003 February 1; 26(1): 61-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12627734&dopt=Abstract

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Pro: modafinil has a role in management of sleep apnea. Author(s): Black J. Source: American Journal of Respiratory and Critical Care Medicine. 2003 January 15; 167(2): 105-6; Discussion 108. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12524247&dopt=Abstract

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Pro: sleep apnea is an anatomic disorder. Author(s): Schwab RJ. Source: American Journal of Respiratory and Critical Care Medicine. 2003 August 1; 168(3): 270-1; Discussion 273. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12888606&dopt=Abstract

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Procedural skill learning in obstructive sleep apnea syndrome. Author(s): Rouleau I, Decary A, Chicoine AJ, Montplaisir J. Source: Sleep. 2002 June 15; 25(4): 401-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12071541&dopt=Abstract

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Prolonged apnea following succinylcholine administration in undiagnosed acute organophosphate poisoning. Author(s): Sener EB, Ustun E, Kocamanoglu S, Tur A. Source: Acta Anaesthesiologica Scandinavica. 2002 September; 46(8): 1046-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12190811&dopt=Abstract

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Prospective polysomnographic analysis of obstructive sleep apnea in down syndrome. Author(s): Dyken ME, Lin-Dyken DC, Poulton S, Zimmerman MB, Sedars E. Source: Archives of Pediatrics & Adolescent Medicine. 2003 July; 157(7): 655-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12860786&dopt=Abstract

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Pulmonary hemodynamics in obstructive sleep apnea: frequency and causes of pulmonary hypertension. Author(s): Hetzel M, Kochs M, Marx N, Woehrle H, Mobarak I, Hombach V, Hetzel J. Source: Lung. 2003; 181(3): 157-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14565689&dopt=Abstract

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Quality of life in bed partners of patients with obstructive sleep apnea or hypopnea after treatment with continuous positive airway pressure. Author(s): Parish JM, Lyng PJ. Source: Chest. 2003 September; 124(3): 942-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12970021&dopt=Abstract

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Radiofrequency ablation for the treatment of mild to moderate obstructive sleep apnea. Author(s): Blumen MB, Dahan S, Fleury B, Hausser-Hauw C, Chabolle F. Source: The Laryngoscope. 2002 November; 112(11): 2086-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12439186&dopt=Abstract

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Raised sympathetic nerve activity in heart failure and central sleep apnea is due to heart failure severity. Author(s): Mansfield D, Kaye DM, Brunner La Rocca H, Solin P, Esler MD, Naughton MT. Source: Circulation. 2003 March 18; 107(10): 1396-400. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12642360&dopt=Abstract

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Randomized crossover trial of two treatments for sleep apnea/hypopnea syndrome: continuous positive airway pressure and mandibular repositioning splint. Author(s): Engleman HM, McDonald JP, Graham D, Lello GE, Kingshott RN, Coleman EL, Mackay TW, Douglas NJ. Source: American Journal of Respiratory and Critical Care Medicine. 2002 September 15; 166(6): 855-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12231497&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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Reduced respiratory-related evoked activity in subjects with obstructive sleep apnea syndrome. Author(s): Akay M, Leiter JC, Daubenspeck JA. Source: Journal of Applied Physiology (Bethesda, Md. : 1985). 2003 February; 94(2): 42938. Epub 2002 December 20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12496135&dopt=Abstract

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Relationship among the severity of sleep apnea syndrome, cardiac arrhythmias, and autonomic imbalance. Author(s): Roche F, Xuong AN, Court-Fortune I, Costes F, Pichot V, Duverney D, Vergnon JM, Gaspoz JM, Barthelemy JC. Source: Pacing and Clinical Electrophysiology : Pace. 2003 March; 26(3): 669-77. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12698666&dopt=Abstract

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Relationship between cephalometric characteristics and obstructive sites in obstructive sleep apnea syndrome. Author(s): Baik UB, Suzuki M, Ikeda K, Sugawara J, Mitani H. Source: Angle Orthod. 2002 April; 72(2): 124-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11999935&dopt=Abstract

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Relationship between quality of life and mood or depression in patients with severe obstructive sleep apnea syndrome. Author(s): Akashiba T, Kawahara S, Akahoshi T, Omori C, Saito O, Majima T, Horie T. Source: Chest. 2002 September; 122(3): 861-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12226024&dopt=Abstract

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Relationship between sleep apnea hypopnea syndrome and cardiovascular events in elderly Chinese snorers. Author(s): Wang H, Zhang X, Yang Y, Yin K, Huang G. Source: Chinese Medical Journal. 2002 December; 115(12): 1829-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12622933&dopt=Abstract

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Relationship between smoking and sleep apnea in clinic population. Author(s): Hoflstein V. Source: Sleep. 2002 August 1; 25(5): 519-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12150318&dopt=Abstract

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Relationship of sleep apnea to functional capacity and length of hospitalization following stroke. Author(s): Kaneko Y, Hajek VE, Zivanovic V, Raboud J, Bradley TD. Source: Sleep. 2003 May 1; 26(3): 293-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12749548&dopt=Abstract

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Relationship of systolic BP to obstructive sleep apnea in patients with heart failure. Author(s): Sin DD, Fitzgerald F, Parker JD, Newton GE, Logan AG, Floras JS, Bradley TD. Source: Chest. 2003 May; 123(5): 1536-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12740271&dopt=Abstract

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Respiratory monitoring by means of an unattended device in children with suspected uncomplicated obstructive sleep apnea: a validation study. Author(s): Zucconi M, Calori G, Castronovo V, Ferini-Strambi L. Source: Chest. 2003 August; 124(2): 602-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12907549&dopt=Abstract

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Retropharyngeal lipoma causing obstructive sleep apnea: case report including fiveyear follow-up. Author(s): Hockstein NG, Anderson TA, Moonis G, Gustafson KS, Mirza N. Source: The Laryngoscope. 2002 September; 112(9): 1603-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12352671&dopt=Abstract

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Role of hypoxemia for the cardiovascular responses to apnea during exercise. Author(s): Lindholm P, Nordh J, Linnarsson D. Source: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. 2002 November; 283(5): R1227-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12376417&dopt=Abstract

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Role of the tongue base suspension suture with The Repose System bone screw in the multilevel surgical management of obstructive sleep apnea. Author(s): Miller FR, Watson D, Malis D. Source: Otolaryngology and Head and Neck Surgery. 2002 April; 126(4): 392-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11997779&dopt=Abstract

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Serum amyloid a in obstructive sleep apnea. Author(s): Svatikova A, Wolk R, Shamsuzzaman AS, Kara T, Olson EJ, Somers VK. Source: Circulation. 2003 September 23; 108(12): 1451-4. Epub 2003 Sep 02. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12952844&dopt=Abstract

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Should flow-volume loop be monitored in sleep apnea patients treated with continuous positive airway pressure? Author(s): Bonay M, Nitenberg A, Maillard D. Source: Respiratory Medicine. 2003 July; 97(7): 830-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12854634&dopt=Abstract

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Sleep apnea: a new 'risk factor' for cardiovascular disease? Author(s): Morgan BJ, Joyner MJ. Source: Exercise and Sport Sciences Reviews. 2002 October; 30(4): 145-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12398109&dopt=Abstract

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Sleep characteristics following adenotonsillectomy in children with obstructive sleep apnea syndrome. Author(s): Tal A, Bar A, Leiberman A, Tarasiuk A. Source: Chest. 2003 September; 124(3): 948-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12970022&dopt=Abstract

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Sleepiness and residual sleepiness in adults with obstructive sleep apnea. Author(s): Black J. Source: Respiratory Physiology & Neurobiology. 2003 July 16; 136(2-3): 211-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12853012&dopt=Abstract

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Sleepwalking through life. Identifying and treating obstructive sleep apnea syndrome. Author(s): Woods DL, Higgins LJ, Dowdy S. Source: Adv Nurse Pract. 2001 May; 9(5): 30-6; Quiz 36-7. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12400257&dopt=Abstract

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Static and dynamic upper airway obstruction in sleep apnea: role of the breathing gas properties. Author(s): Farre R, Rigau J, Montserrat JM, Buscemi L, Ballester E, Navajas D. Source: American Journal of Respiratory and Critical Care Medicine. 2003 September 15; 168(6): 659-63. Epub 2003 July 17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12869358&dopt=Abstract

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Surgical management of maxillomandibular advancement in sleep apnea patients: specific technical considerations. Author(s): Gilon Y, Raskin S, Heymans O, Poirrier R. Source: Int J Adult Orthodon Orthognath Surg. 2001 Winter; 16(4): 305-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12390009&dopt=Abstract

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Surgical management of obstructive sleep apnea. Author(s): Li KK. Source: Clinics in Chest Medicine. 2003 June; 24(2): 365-70. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12800790&dopt=Abstract

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Symptoms related to sleep-disordered breathing in white and Hispanic children: the Tucson Children's Assessment of Sleep Apnea Study. Author(s): Goodwin JL, Babar SI, Kaemingk KL, Rosen GM, Morgan WJ, Sherrill DL, Quan SF; Tucson Children's Assessment of Sleep Apnea Study. Source: Chest. 2003 July; 124(1): 196-203. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12853523&dopt=Abstract

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Taft and Pickwick: sleep apnea in the White House. Author(s): Sotos JG. Source: Chest. 2003 September; 124(3): 1133-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12970047&dopt=Abstract

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The efficacy of anatomically based multilevel surgery for obstructive sleep apnea. Author(s): Kao YH, Shnayder Y, Lee KC. Source: Otolaryngology and Head and Neck Surgery. 2003 October; 129(4): 327-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14574285&dopt=Abstract

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The impact of nocturnal hemodialysis on sleep apnea in ESRD patients. Author(s): Hanly P, Chan C, Pierratos A. Source: Nephrol News Issues. 2003 June; 17(7): 19-21. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12847958&dopt=Abstract

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The length-force relationship of the human genioglossus in patients with obstructive sleep apnea. Author(s): BuSha BF, Strobel RJ, England SJ. Source: Respiratory Physiology & Neurobiology. 2002 April; 130(2): 161-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12380006&dopt=Abstract

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The limitations of isolated palatal surgery for patients with obstructive sleep apnea. Author(s): Dubin MG, Senior BA. Source: Otolaryngologic Clinics of North America. 2003 June; 36(3): 511-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12956098&dopt=Abstract

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The physiologic impact of sleep apnea on wakefulness. Author(s): Goh YH, Lim KA. Source: Otolaryngologic Clinics of North America. 2003 June; 36(3): 423-35, V. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12956092&dopt=Abstract

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Tissue hypoxia in sleep apnea syndrome assessed by uric acid and adenosine. Author(s): Saito H, Nishimura M, Shibuya E, Makita H, Tsujino I, Miyamoto K, Kawakami Y. Source: Chest. 2002 November; 122(5): 1686-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12426272&dopt=Abstract

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Tongue neuromuscular and direct hypoglossal nerve stimulation for obstructive sleep apnea. Author(s): Eisele DW, Schwartz AR, Smith PL. Source: Otolaryngologic Clinics of North America. 2003 June; 36(3): 501-10. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12956097&dopt=Abstract

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Two-point palatal discrimination in patients with upper airway resistance syndrome, obstructive sleep apnea syndrome, and normal control subjects. Author(s): Guilleminault C, Li K, Chen NH, Poyares D. Source: Chest. 2002 September; 122(3): 866-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12226025&dopt=Abstract

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Underdiagnosis of sleep apnea syndrome in U.S. communities. Author(s): Kapur V, Strohl KP, Redline S, Iber C, O'Connor G, Nieto J. Source: Sleep & Breathing = Schlaf & Atmung. 2002 June; 6(2): 49-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12075479&dopt=Abstract

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Unexpected risks during administration of conscious sedation: previously undiagnosed obstructive sleep apnea. Author(s): Sharma VK, Galli W, Haber A, Pressman MR, Stevenson R, Meyer TJ, Peterson DD, Zachariah JS, Mercogliano G, Greenspon L. Source: Annals of Internal Medicine. 2003 October 21; 139(8): 707-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14568871&dopt=Abstract

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Upper airway motion depicted at cine MR imaging performed during sleep: comparison between young Patients with and those without obstructive sleep apnea. Author(s): Donnelly LF, Surdulescu V, Chini BA, Casper KA, Poe SA, Amin RS. Source: Radiology. 2003 April; 227(1): 239-45. Epub 2003 February 28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12616001&dopt=Abstract

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Upper airway size analysis by magnetic resonance imaging of children with obstructive sleep apnea syndrome. Author(s): Arens R, McDonough JM, Corbin AM, Rubin NK, Carroll ME, Pack AI, Liu J, Udupa JK. Source: American Journal of Respiratory and Critical Care Medicine. 2003 January 1; 167(1): 65-70. Epub 2002 October 11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12406826&dopt=Abstract

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Upper airway surgery for obstructive sleep apnea. Author(s): Sher AE. Source: Sleep Medicine Reviews. 2002 June; 6(3): 195-212. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12531121&dopt=Abstract

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Use of nasal cannula for detecting sleep apneas and hypopneas in infants and children. Author(s): Trang H, Leske V, Gaultier C. Source: American Journal of Respiratory and Critical Care Medicine. 2002 August 15; 166(4): 464-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12186821&dopt=Abstract

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Using an air-pad sensor for the diagnosis of sleep apnea: a trial study. Author(s): Miyazaki S, Komatsu N, Takashima M, Tanaka T, Itasaka Y, Yoshizaki K. Source: Psychiatry and Clinical Neurosciences. 2002 June; 56(3): 315-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12047612&dopt=Abstract

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Utility of actigraphy in the diagnosis of obstructive sleep apnea. Author(s): Elbaz M, Roue GM, Lofaso F, Quera Salva MA. Source: Sleep. 2002 August 1; 25(5): 527-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12150319&dopt=Abstract

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Utility of oxygen saturation and heart rate spectral analysis obtained from pulse oximetric recordings in the diagnosis of sleep apnea syndrome. Author(s): Zamarron C, Gude F, Barcala J, Rodriguez JR, Romero PV. Source: Chest. 2003 May; 123(5): 1567-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12740275&dopt=Abstract

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Uvulopalatopharyngoplasty for sleep apnea in mentally retarded obese 14-year-old: an anaesthetic challenge. Author(s): Govindarajan R, Bakalova T, Gerges M, Mendelsohn M, Michael R, Abadir A. Source: Acta Anaesthesiologica Scandinavica. 2003 March; 47(3): 366-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12648207&dopt=Abstract

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Validation of a suprasternal pressure transducer for apnea classification during sleep. Author(s): Meslier N, Simon I, Kouatchet A, Ouksel H, Person C, Racineux JL. Source: Sleep. 2002 November 1; 25(7): 753-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12405611&dopt=Abstract

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Validation of nasal pressure for the identification of apneas/hypopneas during sleep. Author(s): Heitman SJ, Atkar RS, Hajduk EA, Wanner RA, Flemons WW. Source: American Journal of Respiratory and Critical Care Medicine. 2002 August 1; 166(3): 386-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12153976&dopt=Abstract

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Velopharyngeal anatomy in snorers and patients with obstructive sleep apnea. Author(s): Marien S, Schmelzer B. Source: Acta Otorhinolaryngol Belg. 2002; 56(2): 93-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12092332&dopt=Abstract

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Vibrotactile stimulation system to treat apnea of prematurity. Author(s): Pichardo R, Adam JS, Rosow E, Bronzino J, Eisenfeld L. Source: Biomed Instrum Technol. 2003 January-February; 37(1): 34-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12613292&dopt=Abstract

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What are obstructive sleep apnea patients being treated for prior to this diagnosis? Author(s): Smith R, Ronald J, Delaive K, Walld R, Manfreda J, Kryger MH. Source: Chest. 2002 January; 121(1): 164-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11796446&dopt=Abstract

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When does 'mild' obstructive sleep apnea/hypopnea syndrome merit continuous positive airway pressure treatment? Author(s): Engleman HM. Source: American Journal of Respiratory and Critical Care Medicine. 2002 March 15; 165(6): 743-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11897636&dopt=Abstract

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When to suspect obstructive sleep apnea syndrome. Symptoms may be subtle, but treatment is straightforward. Author(s): Attarian HP, Sabri AN. Source: Postgraduate Medicine. 2002 March; 111(3): 70-6; Quiz 14. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11912998&dopt=Abstract

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Women with sleep apnea have lower levels of sex hormones. Author(s): Netzer NC, Eliasson AH, Strohl KP. Source: Sleep & Breathing = Schlaf & Atmung. 2003 March; 7(1): 25-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12712394&dopt=Abstract

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CHAPTER 2. NUTRITION AND APNEA Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and apnea.

Finding Nutrition Studies on Apnea 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 “apnea” (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 “apnea” (or a synonym): •

A single minute lesion around the ventral respiratory group in medulla produces fatal apnea in cats. Author(s): Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan. Source: Hsieh, J H Chang, Y C Su, C K Hwang, J C Yen, C T Chai, C Y J-Auton-NervSyst. 1998 August 27; 73(1): 7-18 0165-1838

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Anesthesia and apnea. Perioperative considerations in the former preterm infant. Author(s): Department of Anesthesiology and Pediatrics, Children's National Medical Center, Washington, DC. Source: Welborn, L G Greenspun, J C Pediatr-Clin-North-Am. 1994 February; 41(1): 18198 0031-3955

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Apnea following spinal anaesthesia in two former pre-term infants. Author(s): Department of Child Health, University of Missouri, Columbia 65212, USA. [email protected] Source: Tobias, J D Burd, R S Helikson, M A Can-J-Anaesth. 1998 October; 45(10): 985-9 0832-610X

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Apnea of prematurity: theophylline v. caffeine. Author(s): Alaska Neonatology Associates, Providence Hospital, Anchorage 99508. Source: Harrison, H Alaska-Med. 1992 Oct-December; 34(4): 173-6 0002-4538

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Caffeine versus theophylline for apnea in preterm infants. Author(s): Mater Childrens Hospital, Raymond Terrace, Brisbane, Australia, 4101. [email protected] Source: Steer, P A Henderson Smart, D J Cochrane-Database-Syst-Revolume 2000; (2): CD000273 1469-493X

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Clonidine and sleep apnea syndrome interaction: antagonism with yohimbine. Author(s): Department of Emergency Medicine, Western Pennsylvania Hospital, Pittsburgh 15224, USA. Source: Roberge, R J Kimball, E T Rossi, J Warren, J J-Emerg-Med. 1998 Sep-October; 16(5): 727-30 0736-4679

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Continuous positive airway pressure versus theophylline for apnea in preterm infants. Author(s): NSW Centre for Perinatal Health Services Research, Queen Elizabeth II Institute for Mothers and Infants, Building DO2, University of Sydney, Sydney, NSW, Australia, 2006. [email protected] Source: Henderson Smart, D J Subramanian, P Davis, P G Cochrane-Database-SystRevolume 2000; (2): CD001072 1469-493X

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Cure of sleep apnea syndrome after long-term nasal continuous positive airway pressure therapy and weight loss. Author(s): Unite d'Explorations Electrophysiologiques du Systeme Nerveux, Cliniques Universitaires St. Luc, Brussels, Belgium. Source: Aubert Tulkens, G Culee, C Rodenstein, D O Sleepage 1989 June; 12(3): 216-22 0161-8105

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Doxapram versus methylxanthine for apnea in preterm infants. Author(s): NSW Centre for Perinatal Health Services Research, Queen Elizabeth II Institute for Mothers and Infants, Building DO2, University of Sydney, Sydney, NSW, AUSTRALIA, 2006. [email protected]

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Source: Henderson Smart, D J Steer, P Cochrane-Database-Syst-Revolume 2000; (4): CD000075 1469-493X •

Effect of autonomic blockade on heart rate and blood pressure in sleep apnea syndrome. Author(s): Laboratoire du Sommeil, INSERM CJF 89 09, Hopital A. Beclere, Clamart, France. Source: Januel, B Laude, D Elghozi, J L Escourrou, P Blood-Press. 1995 July; 4(4): 226-31 0803-7051

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Effectiveness and side effects of two different doses of caffeine in preventing apnea in premature infants. Author(s): Department of Pediatrics, Catholic University of the Sacred Heart, Rome, Italy. Source: Romagnoli, C De Carolis, M P Muzii, U Zecca, E Tortorolo, G Chiarotti, M De Giovanni, N Carnevale, A Ther-Drug-Monit. 1992 February; 14(1): 14-9 0163-4356

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Energy expenditure in obstructive sleep apnea. Author(s): Department of Medicine, University of British Columbia, Vancouver, Canada. Source: Ryan, C F Love, L L Buckley, P A Sleepage 1995 April; 18(3): 180-7 0161-8105

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Fatigue associated with obstructive sleep apnea in a patient with sarcoidosis. Author(s): Department of Pulmonology, University Hospital Maastricht, The Netherlands. [email protected] Source: Drent, M Verbraecken, J van der Grinten, C Wouters, E Respiration. 2000; 67(3): 337-40 0025-7931

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Hormone replacement therapy may alleviate sleep apnea in menopausal women: a pilot study. Author(s): Division of Reproductive Medicine and Infertility, Women and Infants Hospital, Brown University School of Medicine, Providence, RI 02905, USA. Source: Keefe, D L Watson, R Naftolin, F Menopause. 1999 Fall; 6(3): 196-200 1072-3714

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Impact on families caring for an infant with apnea. Source: Sweeney, L B Issues-Compr-Pediatr-Nurs. 1988; 11(1): 1-15 0146-0862

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Influence of chronic barbiturate administration on sleep apnea after hypersomnia presentation: case study. Author(s): Department of Psychiatry, University of Western Ontario. [email protected] Source: Takhar, J Bishop, J J-Psychiatry-Neurosci. 2000 September; 25(4): 321-4 1180-4882

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Kinesthetic stimulation versus theophylline for apnea in preterm infants. Author(s): Department of Neonatal Medicine, Royal Prince Alfred Hospital, Missenden Rd, Camperdown, Sydney, NSW, Australia, 2050. [email protected]. Source: Osborn, D A Henderson Smart, D J Cochrane-Database-Syst-Revolume 2000; (2): CD000502 1469-493X

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Localization of site of obstruction in snorers and patients with obstructive sleep apnea syndrome: a comparison of fiberoptic nasopharyngoscopy and pressure measurements. Author(s): Department of Otorhinolaryngology, Ullevaal University Hospital, Oslo, Norway. Source: Skatvedt, O Acta-Otolaryngol. 1993 March; 113(2): 206-9 0001-6489

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Magnesium therapy in infants with postneonatal apnea. Author(s): Section on Disorders of Carbohydrate Metabolism, National Institutes of Child Health and Human Development, Bethesda, Md. Source: Caddell, J L Magnesium. 1988; 7(2): 103-16 0252-1156

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Medical treatment of sleep apnea. Author(s): Sleep Disorders Center, St. Boniface General Hospital, Winnipeg, Manitoba, Canada. Source: Wali, S O Kryger, M H Curr-Opin-Pulm-Med. 1995 November; 1(6): 498-503 1078-1641

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Methylxanthine treatment for apnea in preterm infants. Author(s): NSW Centre for Perinatal Health Services Research, Queen Elizabeth II Institute for Mothers and Infants, Building DO2, University of Sydney, Sydney, NSW, Australia, 2006. [email protected] Source: Henderson Smart, D J Steer, P Cochrane-Database-Syst-Revolume 2000; (2): CD000140 1469-493X

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Multiple cardiovascular risk factors in obstructive sleep apnea syndrome patients and an attempt at lifestyle modification using telemedicine-based education. Author(s): The Third Department of Internal Medicine and Institute of Physical Fitness Sports Medicine, Aichi Medical University, Japan. Source: Oki, Y Shiomi, T Sasanabe, R Maekawa, M Hirota, I Usui, K Hasegawa, R Kobayashi, T Psychiatry-Clin-Neurosci. 1999 April; 53(2): 311-3 1323-1316

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Nonsurgical management of the obstructive sleep apnea patient. Author(s): Department of Oral and Maxillofacial Surgery, Baylor College of Dentistry, TX, USA. Source: Thornton, W K Roberts, D H J-Oral-Maxillofac-Surg. 1996 September; 54(9): 1103-8 0278-2391

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Obesity and weight loss in obstructive sleep apnea: a critical review. Author(s): Department of Medicine, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick 08903-0019, USA. Source: Strobel, R J Rosen, R C Sleepage 1996 February; 19(2): 104-15 0161-8105

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Obstructive sleep apnea and obesity. Author(s): Baylor College of Medicine, Houston, Texas. Source: Wittels, E H Thompson, S Otolaryngol-Clin-North-Am. 1990 August; 23(4): 75160 0030-6665

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Pathologic apnea and brief respiratory pauses in preterm infants: relation to sleep state. Author(s): School of Nursing, University of North Carolina at Chapel Hill. Source: Holditch Davis, D Edwards, L J Wigger, M C Nurs-Res. 1994 Sep-October; 43(5): 293-300 0029-6562

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Pharmacologic management of apnea of prematurity. Source: Calhoun, L K J-Perinat-Neonatal-Nurs. 1996 March; 9(4): 56-62 0893-2190

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Pharmacotherapies for obstructive sleep apnea: how close are we? Author(s): Division of Sleep Medicine and Pulmonary, Department of Medicine, University of Pennsylvania, School of Medicine, Philadelphia, Pennsylvania 19104-4283, USA. [email protected] Source: Veasey, S C Curr-Opin-Pulm-Med. 2001 November; 7(6): 399-403 1070-5287

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Postoperative caffeine for preventing apnea in preterm infants. Author(s): NSW Centre for Perinatal Health Services Research, Queen Elizabeth II Institute for Mothers and Infants, Building DO2, University of Sydney, Sydney, NSW, Australia, 2006. [email protected] Source: Henderson Smart, D J Steer, P Cochrane-Database-Syst-Revolume 2000; (2): CD000048 1469-493X

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Prophylactic caffeine to prevent postoperative apnea following general anesthesia in preterm infants (Cochrane Review). Author(s): NSW Centre for Perinatal Health Services Research, Queen Elizabeth II Institute for Mothers and Infants, Building DO2, University of Sydney, Sydney, NSW, AUSTRALIA, 2006. [email protected] Source: Henderson Smart, D J Steer, P Cochrane-Database-Syst-Revolume 2001; 4: CD000048 1469-493X

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Reduced prostacyclin to thromboxane A2 ratio is correlated with central apneas in preterm infants. Author(s): Department of Pediatrics, Philipps-University of Marburg, Germany. Source: Hoch, B Bernhard, M Prostaglandins-Other-Lipid-Mediat. 1999 November; 58(56): 285-90 1098-8823

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Respiratory arrest following intrathecal injection of sufentanil and bupivacaine in a parturient. Author(s): Department of Anaesthesia, Women's College Hospital, University of Toronto, Ontario, Canada. Source: Katsiris, S Williams, S Leighton, B L Halpern, S Can-J-Anaesth. 1998 September; 45(9): 880-3 0832-610X

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Saliva as a valid alternative to serum in monitoring intravenous caffeine treatment for apnea of prematurity. Author(s): Department of Pharmacy, University of Queensland, Brisbane, Australia. Source: Lee, T C Charles, B G Steer, P A Flenady, V J Ther-Drug-Monit. 1996 June; 18(3): 288-93 0163-4356

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Susceptibility of LDL to oxidative stress in obstructive sleep apnea. Author(s): Sleep Disorders Center, St. Boniface General Hospital, Winnipeg, Manitoba. Source: Wali, S O Bahammam, A S Massaeli, H Pierce, G N Iliskovic, N Singal, P K Kryger, M H Sleepage 1998 May 1; 21(3): 290-6 0161-8105

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The effect of sleep apnea on plasma and urinary catecholamines. Author(s): Department of Psychiatry, University of California, San Diego, La Jolla 920930804, USA. Source: Dimsdale, J E Coy, T Ziegler, M G Ancoli Israel, S Clausen, J Sleepage 1995 June; 18(5): 377-81 0161-8105

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Theophylline or caffeine: which is best for apnea of prematurity? Author(s): Women and Infants' Hospital, 101 Dudley Street, Providence, RI 02905-2401, USA. [email protected] Source: Gannon, B A Neonatal-Netw. 2000 December; 19(8): 33-6 0730-0832

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Transition times to oral feeding in premature infants with and without apnea. Author(s): Division of Physical Therapy, West Virginia University, Morgantown 265069226, USA. Source: Mandich, M B Ritchie, S K Mullett, M J-Obstet-Gynecol-Neonatal-Nurs. 1996 Nov-December; 25(9): 771-6 0884-2175

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Treatment of obstructive sleep apnea syndrome with a Kampo-formula, San'oshashin-to: a case report. Author(s): Department of Neuropsychiatry, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Japan. Source: Hisanaga, A Saitoh, O Fukuda, H Kurokawa, K Okabe, A Tachibana, H Hagino, H Mita, T Yamashita, I Tsutsumi, M Kurachi, M Itoh, T Psychiatry-Clin-Neurosci. 1999 April; 53(2): 303-5 1323-1316

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Treatment outcome of sleep apnea. Author(s): New Haven Sleep Disorders Center, CT 06511. Source: Watson, R K Thompson, A S Conn-Med. 1992 March; 56(3): 125-9 0010-6178

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Velopharyngeal insufficiency versus adenoidectomy for obstructive apnea: a quandary. Author(s): Pediatric Otolaryngology Associates, San Diego, CA 92103. Source: Seid, A B Cleft-Palate-J. 1990 April; 27(2): 200-2 0009-8701

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

Nutrition

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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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CHAPTER 3. ALTERNATIVE MEDICINE AND APNEA Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to apnea. 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 apnea 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 “apnea” (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 apnea: •

Altered brainstem sensory processing as assessed by reflex modification procedures in infants at risk for apnea. Author(s): Anday EK, Cohen ME, Daumit G, Hoffman HS. Source: Pediatric Research. 1989 December; 26(6): 576-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2602037&dopt=Abstract

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Alternative therapies for sleep apnea. Author(s): Ayas NT, Malhotra A, Epstein LJ. Source: Drugs Today (Barc). 1999 November; 35(11): 811-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12973373&dopt=Abstract

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An animal model for airway sensory deprivation producing obstructive apnea with postmortem findings of sudden infant death syndrome. Author(s): Abu-Osba YK, Mathew OP, Thach BT.

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Source: Pediatrics. 1981 December; 68(6): 796-801. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7322715&dopt=Abstract •

Apnea in postsurgical hypnotherapy of an esophageal cancer patient: a brief communication. Author(s): Jones MM. Source: Int J Clin Exp Hypn. 1994 July; 42(3): 179-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8063459&dopt=Abstract

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Automobile driving in sleep apnea. Author(s): Findley LJ. Source: Prog Clin Biol Res. 1990; 345: 337-43; Discussion 344-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2198595&dopt=Abstract

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Brainstem auditory evoked potentials in adult and infant sleep apnea syndromes, including sudden infant death syndrome and near-miss for sudden infant death. Author(s): Stockard JJ. Source: Annals of the New York Academy of Sciences. 1982; 388: 443-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6953881&dopt=Abstract

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Changes in genioglossus muscle activity in obstructive sleep apnea patients with and without snore guard. Author(s): Zhao Y, Zeng X, Fu M, Huang X. Source: Chin J Dent Res. 2000 May; 3(1): 12-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11314334&dopt=Abstract

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Clinical effects of L-carnitine supplementation on apnea and growth in very low birth weight infants. Author(s): Whitfield J, Smith T, Sollohub H, Sweetman L, Roe CR. Source: Pediatrics. 2003 March; 111(3): 477-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12612224&dopt=Abstract

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Conditioned hyperventilation as a factor in animal, infant, and adult apnea: a theoretical analysis of experimental and clinical data. Author(s): Caldwell WE. Source: Genetic, Social, and General Psychology Monographs. 1986 August; 112(3): 32541. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3770464&dopt=Abstract

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Effect of gender on the development of hypocapnic apnea/hypopnea during NREM sleep. Author(s): Zhou XS, Shahabuddin S, Zahn BR, Babcock MA, Badr MS.

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Source: Journal of Applied Physiology (Bethesda, Md. : 1985). 2000 July; 89(1): 192-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10904052&dopt=Abstract •

Effect of induced transient arousal on obstructive apnea duration. Author(s): Basner RC, Onal E, Carley DW, Stepanski EJ, Lopata M. Source: Journal of Applied Physiology (Bethesda, Md. : 1985). 1995 April; 78(4): 1469-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7615457&dopt=Abstract

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Electrostimulation in apnea after ECT. Author(s): MEADOWS R Jr. Source: The American Journal of Psychiatry. 1955 February; 111(8): 620-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13228719&dopt=Abstract

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Factors related to the efficacy of an adjustable oral appliance for the treatment of obstructive sleep apnea. Author(s): Liu Y, Lowe AA. Source: Chin J Dent Res. 2000 November; 3(3): 15-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11314530&dopt=Abstract

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First results on daytime submandibular electrostimulation of suprahyoidal muscles to prevent night-time hypopharyngeal collapse in obstructive sleep apnea syndrome. Author(s): Wiltfang J, Klotz S, Wiltfang J, Jordan W, Cohrs S, Engelbe W, Hajak G. Source: International Journal of Oral and Maxillofacial Surgery. 1999 February; 28(1): 215. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10065643&dopt=Abstract

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Hyperekplexia: report of a nonfamilial adult onset case associated with obstructive sleep apnea and abnormal brain nuclear tomography. Author(s): Hochman MS, Chediak AD, Ziffer JA. Source: Sleep. 1994 April; 17(3): 280-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7939129&dopt=Abstract

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Kinesthetic stimulation for preventing apnea in preterm infants. Author(s): Henderson-Smart DJ, Osborn DA. Source: Cochrane Database Syst Rev. 2002; (2): Cd000373. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12076395&dopt=Abstract

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Kinesthetic stimulation for preventing apnea in preterm infants. Author(s): Henderson-Smart DJ, Osborn DA. Source: Cochrane Database Syst Rev. 2000; (2): Cd000373. Review. Update In: http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10796201&dopt=Abstract

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Kinesthetic stimulation versus theophylline for apnea in preterm infants. Author(s): Osborn DA, Henderson-Smart DJ. Source: Cochrane Database Syst Rev. 2000; (2): Cd000502. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10796214&dopt=Abstract

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Lack of effect of external warming on sleep architecture in sleep apnea/hypopnea syndrome. Author(s): Dowdell WT, Javaheri S. Source: Am Rev Respir Dis. 1992 January; 145(1): 137-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1731577&dopt=Abstract

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Laser-assisted uvulopalatoplasty for the treatment of mild, moderate, and severe obstructive sleep apnea. Author(s): Walker RP, Grigg-Damberger MM, Gopalsami C. Source: The Laryngoscope. 1999 January; 109(1): 79-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9917045&dopt=Abstract

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Magnetic therapy is ineffective for the treatment of snoring and obstructive sleep apnea syndrome. Author(s): Dexter D Jr. Source: Wis Med J. 1997 March; 96(3): 35-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9086856&dopt=Abstract

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Metabolic rate, respiratory exchange ratio, and apneas during meditation. Author(s): Kesterson J, Clinch NF. Source: The American Journal of Physiology. 1989 March; 256(3 Pt 2): R632-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2493750&dopt=Abstract

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Modification of conditioned apneas in rats: evidence for cortical involvement. Author(s): Thomas AJ, Friedman L, MacKenzie CN, Strohl KP. Source: Journal of Applied Physiology (Bethesda, Md. : 1985). 1995 April; 78(4): 1215-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7615426&dopt=Abstract

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Molecular and physiologic basis of obstructive sleep apnea. Author(s): Veasey SC. Source: Clinics in Chest Medicine. 2003 June; 24(2): 179-93. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12800777&dopt=Abstract

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Obstructive sleep apnea secondary to chronic lymphocytic leukemia. Author(s): Chehal A, Haidar JH, Jabbour R, Yammout B, Bazarbachi A.

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Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2002 November; 13(11): 1833. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12419760&dopt=Abstract •

Obstructive sleep apnea syndrome as first manifestation of pharyngeal nonHodgkin's lymphoma. Author(s): Gomez-Merino E, Arriero JM, Chiner E, Signes-Costa J, Marco J. Source: Respiration; International Review of Thoracic Diseases. 2003 January-February; 70(1): 107-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12584402&dopt=Abstract

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Peripheral and central ventilatory responses in central sleep apnea with and without congestive heart failure. Author(s): Solin P, Roebuck T, Johns DP, Walters EH, Naughton MT. Source: American Journal of Respiratory and Critical Care Medicine. 2000 December; 162(6): 2194-200. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11112137&dopt=Abstract

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Reduced inspiratory drive following laryngeal chemoreflex apnea during hypoxia. Author(s): Milerad J, Sundell HW. Source: Respiration Physiology. 1999 June 1; 116(1): 35-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10421032&dopt=Abstract

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Role of L-carnitine in apnea of prematurity: a randomized, controlled trial. Author(s): O'Donnell J, Finer NN, Rich W, Barshop BA, Barrington KJ. Source: Pediatrics. 2002 April; 109(4): 622-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11927706&dopt=Abstract

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Successful treatment of sleep apnea syndrome by transfusion of “vital energy”. Author(s): Zhu SS. Source: Chinese Medical Journal. 1980 April; 93(4): 279-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6768528&dopt=Abstract

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The art and science of continuous positive airway pressure therapy in obstructive sleep apnea. Author(s): Malhotra A, Ayas NT, Epstein LJ. Source: Current Opinion in Pulmonary Medicine. 2000 November; 6(6): 490-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11100958&dopt=Abstract

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The effect of treatment on diaphragm contractility in obstructive sleep apnea syndrome. Author(s): El-Kabir DR, Polkey MI, Lyall RA, Williams AJ, Moxham J.

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Source: Respiratory Medicine. 2003 September; 97(9): 1021-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14509556&dopt=Abstract •

The effects of transcutaneous electrical stimulation during wakefulness and sleep in patients with obstructive sleep apnea. Author(s): Edmonds LC, Daniels BK, Stanson AW, Sheedy PF 3rd, Shepard JW Jr. Source: Am Rev Respir Dis. 1992 October; 146(4): 1030-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1416392&dopt=Abstract

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Treatment of apnea in neonates with an automated monitor-actuated apnea arrestor. Author(s): Frank UA, Bordiuk JM, Borromeo-McGrail V, Saltzman MB, Keitel HG. Source: Pediatrics. 1973 May; 51(5): 878-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4703399&dopt=Abstract

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Treatment of obstructive sleep apnea syndrome with a Kampo-formula, San'oshashin-to: a case report. Author(s): Hisanaga A, Saitoh O, Fukuda H, Kurokawa K, Okabe A, Tachibana H, Hagino H, Mita T, Yamashita I, Tsutsumi M, Kurachi M, Itoh T. Source: Psychiatry and Clinical Neurosciences. 1999 April; 53(2): 303-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10459719&dopt=Abstract

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Ventilatory dynamics of transient arousal in patients with obstructive sleep apnea. Author(s): Khoo MC, Shin JJ, Asyali MH, Kim TS, Berry RB. Source: Respiration Physiology. 1998 June; 112(3): 291-303. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9749952&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 apnea; 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 Amyloidosis Source: Integrative Medicine Communications; www.drkoop.com High Blood Pressure Source: Integrative Medicine Communications; www.drkoop.com Hypoparathyroidism Source: Integrative Medicine Communications; www.drkoop.com Insomnia Source: Integrative Medicine Communications; www.drkoop.com Meningitis Source: Integrative Medicine Communications; www.drkoop.com Obesity Source: Integrative Medicine Communications; www.drkoop.com Pulmonary Hypertension Source: Integrative Medicine Communications; www.drkoop.com Sleeplessness Source: Integrative Medicine Communications; www.drkoop.com

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Herbs and Supplements Piper Nigrum Alternative names: Black Pepper Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org

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.

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

Dissertations on Apnea 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 apnea. 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 Predictive Model of Health-related Quality of Life in Obstructive Sleep Apnea by Hanley, Marisol A.; Phd from State University of New York at Buffalo, 2002, 159 pages http://wwwlib.umi.com/dissertations/fullcit/3052512

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Assessment of Respiratory Mechanics in Humans: Application to Subjects Predisposed to Apnea by Bijaoui, Eve Lucienne; Phd from Universite De Montreal (canada), 2002, 214 pages http://wwwlib.umi.com/dissertations/fullcit/NQ67772

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Cognitive and Behavioral Effects of Obstructive Sleep Apnea in Toddlers with Down Syndrome by Gaither, Rebecca Ann; Phd from Illinois Institute of Technology, 2003, 49 pages http://wwwlib.umi.com/dissertations/fullcit/3087837

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Genetics of Sleep Apnea by Buxbaum, Sarah Gail; Phd from Case Western Reserve University (health Sciences), 2002, 114 pages http://wwwlib.umi.com/dissertations/fullcit/3058831

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Re-intubation in Premature Infants As a Result of Apnea by Bellflower, Bobby Burrell; Dnsc from The University of Tennessee Center for the Health Sciences, 2002, 31 pages http://wwwlib.umi.com/dissertations/fullcit/3080967

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Self-report Sleepiness Measures, Objective Sleepiness Measures and Simulated Driving Performance in Controls and Patients with Obstructive Sleep Apnea by Alloway, Christine Elizabeth Darnaby; Phd from Queen's University at Kingston (canada), 2002, 202 pages http://wwwlib.umi.com/dissertations/fullcit/NQ69358

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Social Work Intervention to Increase Compliance with Home Apnea Monitoring by Baker, Lisa Renee Pearson, Phd from University of Georgia, 1998, 104 pages http://wwwlib.umi.com/dissertations/fullcit/9919995

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The Associations of Cardiovascular Risk Factors and Sleep Apnea with White Matter Disease in the Brain Stem by Ding, Jingzhong; Phd from The Johns Hopkins University, 2002, 130 pages http://wwwlib.umi.com/dissertations/fullcit/3028258

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The Effects of a Cervical Collar in the Treatment of Apnea of Prematurity by Munro, Denise Florence; Mn from University of Alberta (canada), 2002, 104 pages http://wwwlib.umi.com/dissertations/fullcit/MQ69673

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Treatment Effects with a Mandibular Advancement Appliance and Uvulopalatopharyngoplasty in Obstructive Sleep Apnea: Randomised Controlled Trials by Walker-engstrom, Marie-louise; Phd from Uppsala Universitet (sweden), 2003, 88 pages http://wwwlib.umi.com/dissertations/fullcit/f148513

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Ventilation and Lung Volume during Sleep and in Obstructive Sleep Apnea by Appelberg, Jonas; Phd from Uppsala Universitet (sweden), 2003, 76 pages http://wwwlib.umi.com/dissertations/fullcit/f13633

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 APNEA Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning apnea.

Recent Trials on Apnea The following is a list of recent trials dedicated to apnea.8 Further information on a trial is available at the Web site indicated. •

APPLES: Apnea Positive Pressure Long-Term Efficacy Study Condition(s): Lung Diseases; Sleep Apnea Syndromes; Sleep Study Status: This study is currently recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To determine the effectiveness of nasal continuous positive airway pressure (CPAP) therapy for the treatment of obstructive sleep apnea syndrome. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00051363

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Effects of Treating Obstructive Sleep Apnea in Epilepsy Condition(s): Epilepsy; Sleep Apnea; Obstructive Sleep Apnea Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Neurological Disorders and Stroke (NINDS) Purpose - Excerpt: The purpose of this trial is to determine whether treating sleeprelated breathing disorders in people with epilepsy results in improvement in seizure control or an improvement in alertness during the day. Phase(s): Phase II

8

These are listed at www.ClinicalTrials.gov.

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Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00047463 •

Safety and Efficacy of Xenical in Children and Adolescents with Obesity-Related Diseases Condition(s): Diabetes Mellitus; Hypertension; Metabolic Disease; Obesity; Sleep Apnea Syndrome Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Child Health and Human Development (NICHD) Purpose - Excerpt: Obesity is a condition affecting one-third off the U.S. population and is a major risk actor for the development of Type 2 diabetes, hyperlipidemia (increased levels of fat in the blood), hypertension (high blood pressure), and other disorders of the heart and lungs. Individuals with the onset of obesity during childhood or adolescence are at an increased risk of obesity-related, diseases, both during adolescence and later in adult life. African American girls and women are at an increased risk for obesity, and have substantial rates of obesity-related diseases and causes of death. Further, many African American adult women fail to respond to many of the therapeutic approaches used to treat obesity. At present there are no medical therapies proven effective for the correction of severe obesity in children or adolescents. One medication that may have a favorable risk-benefit ratio in pediatric populations is Orlistat (Xenical, Hoffmann LaRoche). Orlistat works by preventing the action of enzymes in the digestive process, interfering with the absorption of approximately 1/3 of the fat eaten in the diet. Xenical appears to be effective for reducing weight and obesity-associated diseases in obese adults. Researchers propose to determine the safety, tolerability, and efficacy of Xenical in 12-17 year old severely obese African American and Caucasian children and adolescents who have one or more obesity-related disease (hypertension, hyperlipidemia, sleep apnea, hepatic steatosis, insulin resistance, impaired glucose tolerance, or Type 2 diabetes). Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001723

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Outcomes of Sleep Disorders in Older Men Condition(s): Cardiovascular Diseases; Heart Diseases; Sleep; Sleep Apnea Syndromes; Neurologic Manifestations; Osteoporosis; Bone Diseases Study Status: This study is not yet open for patient recruitment. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To determine the effects of sleep disorders on cardiovascular function and disease in older men. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00070681

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Prevalence of Sleep Disordered Breathing in Children Condition(s): Lung Diseases; Sleep Apnea Syndromes Study Status: This study is not yet open for patient recruitment. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To investigate the prevalence and clinical significance of sleep disordered breathing (SDB) in children. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00022789

Keeping Current on Clinical Trials The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to the Web site at http://www.clinicaltrials.gov/ and search by “apnea” (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 APNEA 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 “apnea” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on apnea, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Apnea By performing a patent search focusing on apnea, 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 apnea: •

Active implantable medical device for treating sleep apnea syndrome by electrostimulation Inventor(s): Bonnet; Jean-Luc (Monrouge, FR) Assignee(s): Ela Medical S.A. (Montrouge, FR) Patent Number: 6,574,507 Date filed: March 6, 2000 Abstract: An active implantable medical device for electrostimulation in response to a determined sleep apnea syndrome, particularly a pacemaker. This device measures the respiratory activity of the patient, using for example, a minute ventilation sensor and/or a blood oxygen saturation sensor, and analyzes the sensor signal, to determine occurrence of an apnea according to the signal delivered by the sensor. The device also delivers an increase cardiiac pacing rate in the event of detection of apnea. The device also can deliver a neurological and/or cardiac stimulation so as to apply selectively to the patient an electric stimulus. The device also determines the patients's state of activity, according to predetermined criteria, such that the increased pacing rate is provided only during a sleep phase and otherwise inhibited. The analysis can in particular detect and occurrence of successive apnea during a phase of sleep and determine the occurrence of a sleep apnea syndrome when the number of apnea events detected during a given period of time exceeds a predetermined threshold. Excerpt(s): The present invention relates to the diagnosis of the syndrome of sleep apnea and more particularly, cardiac pacemakers able to detect sleep apnea and respond to the detection with electrostimulation. The syndrome of sleep apnea ("SAS"), more precisely the syndrome of obstructive and non central sleep apnea ("SOAS") is an affliction having generally as its origin an obstruction of the respiratory tracts. It is likely to involve a certain number of disorders such as painful and/or insufficient breathing, an abnormal heartbeat, and hypertension. Various treatments of SAS have been proposed, including treatments involving surgery, medication, and maintenance of a positive pressure in the respiratory tract by means of a facial mask worn during sleep. One technique, as discussed in EP-A-0 702 979 (to Medtronic) proposes to treat SAS by electrostimulation. This document describes an implanted pulse generator, controlled by a sensor, which may be a dynamic pressure sensor or a sensor of intrathoracic impedance, making it possible to follow (monitor) the patient's respiration rate and thus to detect the occurrence of an apnea. When an apnea is detected, the generator delivers a salvo (sequence) of pulses to a stimulation electrode implanted in the muscles controlling the patient's airway. This technique is not, however, in practice, completely satisfactory. This is because the stimulation which is systematically started in the event of an increase in the intratracheal pressure, whatever the cause of this increase in pressure, and whether it is due to an SAS or not, will include inappropriate stimulations. Web site: http://www.delphion.com/details?pn=US06574507__

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Apnea detector with artifact rejection Inventor(s): Lambert; Scott (East Bethel, MN) Assignee(s): Cas Medical Systems, Inc. (Branford, CT) Patent Number: 6,537,228 Date filed: April 24, 2001 Abstract: A method and apparatus in an apnea detector monitor impedance pneumographic respiratory signals and heart rate of a patient. Magnitudes of excursions of the respiratory signals are monitored to resolve respiratory events, i.e. breaths, inhalations and exhalations. A counter will reach a threshold count and trigger an alarm if a selected interval lapses without a respiratory event being detected. If a respiratory event is detected, as by detecting successive peaks, a peak or a valley of the respiratory signal, the timer is reset. The method and apparatus reject artifact that would otherwise appear as breathing cycles in order to prevent false negative indications of apnea. Cyclically occurring peaks are rejected as being indicative of a breath if they are in a selected magnitude range compared to that of a normal breath and they approximate the patient's heart rate. Successive peaks due to sighs or of a baseline change are measured for average rate of change over the period it takes for the waveform to decrease from the second peak by of a selected level generally corresponding to of a normal inhalation or exhalation. They are rejected as artifact if the change is too slow. Consequently, sighs are not misinterpreted as breaths. Excerpt(s): The present invention relates to electronic respiratory monitoring and more particularly to an apnea detection method and apparatus for rejecting artifact and reducing false negative indications of apnea. Apnea, from the Greek for "a want of breath," is an interruption in breathing. Apnea or cessation of breathing may be a significant event for people of any age, but is particularly significant in a newborn. Consequences of apnea range from merely annoying to life-threatening. Various prior art schemes have been provided to monitor breathing for the purpose of detecting apnea. Pneumatic systems measure actual air flow. Others measure sounds. A more powerful diagnostic tool has been found in the electronic monitoring of breathing and heartbeat waveforms. For example, U.S. Pat. No. 5,206,807, issued Apr. 27, 1993 and entitled Neonatal Cardiorespirograph Incorporating Multi-Variable Display and Memory, illustrates a system sensors and transducers providing signals indicative of cardiac activity, respiratory effort and relative saturation of oxyhemoglobin and transmits them to a computer. The respiratory effort may be measured by impedance pneumography. The computer produces many outputs including a real time electrocardiogram (ECG) waveform and a display of respiratory effort versus time. These two plots may be combined in a cardiorespirogram (CRG). The system provides a user-settable apnea alarm which is variable from five to 30 second intervals after a last breath. Generally, a delay in breathing over 20 seconds is considered to be an apneic event. Web site: http://www.delphion.com/details?pn=US06537228__

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Apparatus and method for providing a breathing gas employing a bi-level flow generator with an AC synchronous motor Inventor(s): Campbell; James L. (Plymouth, MN), Delache; Alain J. (Nice, FR), Emerson; Paul F. (St. Louis Park, MN), Souquet; Jacques (Nice, FR) Assignee(s): Mallinckrodt Inc. (St. Louis, MO) Patent Number: 6,644,310 Date filed: September 29, 2000 Abstract: An apparatus and method for treating sleep apnea includes a bilevel flow generator having an alternating current (AC) synchronous motor coupled to a low inertia centrifugal rotor/impeller. The process of acceleration and deceleration of the rotor involves moving from frequency A, amplitude A to frequency B, amplitude B in an optimal linear fashion using the so-called Bresenham algorithm. This is coupled with a tuned increase of the amplitude during the acceleration process which will produce the acceleration using minimum current allowing the use of smaller power supplies. During deceleration the process is accomplished in reverse fashion using a tuned decrease of the amplitude coupled with a special shunt circuit to prevent power supply voltage changes. These changes in amplitude overlay a current feedback mechanism used to prevent loss of synchronization of the motor by changing amplitude. Speed changes can also be timed so as to prevent desynchronization. Excerpt(s): The present invention relates to an apparatus and method for delivering a breathing gas to a user at alternating levels of pressure as a treatment for respiratory conditions such as sleep apnea. The sleep apnea syndrome affects some 1% to 5% of the general population and is due to upper airway obstruction during sleep. The direct consequences of sleep apnea are sleep fragmentation, partial cessation of ventilation and oxyhemoglobin desaturation. These in turn translate into daytime somnolence, cardiac arrhythmia, congestive heart failure and a variety of other health as well as cognitive dysfunctions. All of these have secondary social and behavioral effects which can result in increased patient morbidity as well as possible mortality if they are engaged in activities which require alertness (such as driving a car). The causes of upper airway obstruction are varied but may include anatomical changes leading to a narrowing of the pathway, loss of muscle tone and/or increased weight of the structures. Age and obesity appear to be risk factors suggesting that an excess of soft tissue in the neck may provide sufficient pressure on internal structures to compromise the patency of the airway. Web site: http://www.delphion.com/details?pn=US06644310__

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Apparatus and methods for treatment of conditions including obstructive sleep apnea and snoring Inventor(s): Palmisano; Richard George (8/9 Guilfoyle Ave., Double Bay, New South Wales 2028, AU) Assignee(s): none reported Patent Number: 6,536,439 Date filed: September 30, 1997 Abstract: Apparatus and methods for the treatment of conditions including obstructive sleep apnea and/or snoring resulting from excessive nasal airway resistance are

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disclosed. A rapid maxillary expansion device (10) is fitted to teeth (12, 14) of the upper jaw, and by operation of the jack screw (20), the maxilla is expanded such that, usually, the intermaxillary suture opens. The expansion is maintained until the maxilla stabilizes, for example by new bone growth along the suture. In this way the minimum crosssectional area of the nasal cavity increases, reducing nasal airway resistance and curing, or at least ameliorating, obstructive sleep apnea and/or snoring. Excerpt(s): This invention relates to apparatus and methods for the treatment of conditions including obstructive sleep apnea (OSA) and snoring. The invention is believed also to relate to the treatment of other upper respiratory conditions. The preferred clinical treatment for OSA is Continuous Positive Airway Pressure (CPAP) which acts to alleviate the occurrence of apneas and hypopneas during sleep. CPAP is the technique of pneumatically splinting the airway open by supplying air at a pressure elevated above atmospheric pressure to the nose, or to the nose and mouth. It is not, however, a curative treatment. Surgical techniques are also known, however they are radical treatments that have generally been disappointing as a curative. Web site: http://www.delphion.com/details?pn=US06536439__ •

Apparatus for the diagnosis or treatment of respiratory sleep disorders and operating process Inventor(s): Vega; Enrique (Paris, FR) Assignee(s): Taema (Antony, FR) Patent Number: 6,475,156 Date filed: June 13, 2000 Abstract: The apparatus includes a motorized turbine making it possible to deliver a stream of respiratory gas under variable or constant pressure into a patient circuit linked to a user. In the process an image of the respiratory flow rate of the patient is determined on the basis of the variations in the electric current consumed by the turbine. An image of the respiratory volume of the patient is determined by integrating the image of the respiratory flow rate of the patient. The moving average of the image of the respiratory volume of the patient is determined over n respiratory cycles and a respiratory flow rate restriction is determined, below that of an apnea or a hypopnea, representative of an event of ORE type. Excerpt(s): The present invention relates to a process for operating or for controlling an artificial ventilation apparatus making it possible to diagnose or to treat sleep disorders of ORE type, during which a patient is subject to restrictions of his respiratory volume which are smaller than those occurring during a period of apnea or of hypopnea, but nevertheless of sufficient concern to require treatment, as well as to such an apparatus. At present, numerous apparatuses for the artificial ventilation of a patient make it possible to ensure effective detection of certain respiratory sleep disorders, namely apneas or hypopneas. An apnea is defined as a sleep disorder which is characterized in an individual by stoppage of respiratory activity for a variable period of time during his sleep, that is to say a reduction of more than 90% in the amplitude of the normal respiratory flow rate of this individual. Web site: http://www.delphion.com/details?pn=US06475156__

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Automatic rise time adjustment for bi-level pressure support system Inventor(s): Yurko; Gregory (Murrysville, PA) Assignee(s): Respironics, Inc. (Murrysville, PA) Patent Number: 6,532,960 Date filed: June 29, 2001 Abstract: An apparatus and method for a bi-level positive airway pressure support in which the rise time from the expiratory positive airway pressure to the inspiratory positive airway pressure is automatically controlled by the pressure support system. The pressure support system includes a sensor, a control system, and a pressure generating system. The sensor monitors the patient's respiration to detect respiratory events, such as an apnea, hyponea or other disturbance, and the control system responds to the sensor information to adjust the rise time from the expiratory positive airway pressure to the inspiratory positive airway pressure gas pressure to maximize patient comfort and pressure support treatment effectiveness. Excerpt(s): The present invention generally relates to a bi-level positive airway pressure support system, and, more particularly, to a bi-level pressure support system and method of providing bi-level pressure support in which the rise time from the expiratory phase of pressure support to the inspiratory phase is automatically adjusted. Pressure support systems that provide a flow of breathing to an airway of a patient at an elevated pressure to treat a medical disorder are well known. One basic form of pressure support system is a continuous positive airway pressure (CPAP) system, which typically involves providing a flow of breathing gas, such as air, to a patient's airway at a constant pressure throughout a patient's breathing cycle. When used to treat obstructive sleep apnea (OSA), for example, this constant pressure is provided at a level sufficient to overcome a patient's airway resistances. It is also known to provide a bi-level positive pressure therapy in which the pressure of gas delivered to the patient varies with the patient's breathing cycle. In a bi-level pressure support system, an inspiratory positive airway pressure (IPAP) is provided during a patient's inspiratory phase of the breathing cycle and an expiratory positive airway pressure (EPAP) is provided during the expiratory phase. The EPAP is lower than the IPAP so that the patient exhales against relatively low pressure as compared to the IPAP pressure, thereby increasing the comfort to the patient. The BiPAP.RTM. family of pressure support devices manufactured by Respironics, Inc. of Murrysville, Pa., are examples of pressure support device that provide this bi-level form of pressure support therapy. In addition, several U.S. patents describe this bi-level pressure support system in detail, including U.S. Pat. Nos. 5,433,193; 5,313,937; 5,239,995; and 5,148,802, all of which are hereby expressly incorporated herein by reference as if set forth in their entirety herein. Web site: http://www.delphion.com/details?pn=US06532960__

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Cloning and expression of dog gonadotropin releasing hormone receptor Inventor(s): Cui; Jisong (Scotch Plains, NJ), Lo; Jane-Ling (North Brunswick, NJ), Mount; George R. (Morrisville, PA) Assignee(s): Merck & Co., Inc. (Rahway, NJ) Patent Number: 6,407,222 Date filed: May 31, 2000

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Abstract: The dog GnRH receptor has been isolated, cloned and sequenced. The dog GnRH receptor may be used to screen and identify compounds which bind to the GnRH receptor. Such identified compounds may be used in the treatment of sex hormone related conditions such as endometriosis, uterine fibroids, polycystic ovarian disease, hirsutism, precocious puberty, gonadal steroid-dependent neoplasias such as cancers of the prostate, breast and ovary, gonadotrophe pituitary adenomas, sleep apnea, irritable bowel syndrome, premenstrual syndrome and benign prostatic hypertrophy. The receptor proteins and polypeptides, nucleic acids, cells and assays of this invention are useful in drug screening and development, diagnosis and therapeutic applications. Excerpt(s): This invention relates to the cloning and isolation of the dog gonadotropinreleasing hormone (GnRH) receptor, and also to mutant or polymorphic forms of the receptor and recombinant nucleic acids encoding the same. The invention also relates to genetically engineered host cells which express the receptor, antibodies against the receptor and polypeptides thereof. The invention also relates to uses of the receptor, recombinant nucleic acids and recombinant host cells in drug screening and development, diagnosis and therapeutic applications. Gonadotropin-releasing hormone (GnRH) plays a pivotal role in the control of reproduction. It is a neuronal decapeptide hormone released from hypothalamus in a pulsatile manner. GnRH interacts with its receptor on the gonadotropes in the anterior pituitary and which, in turn, activates phospholipase C (PLC) via a pertussis toxin-insensitive G protein, Gq/G11. Two second messengers, inositol trisphosphate (IP3) and diacylglycerol (DG), are formed from the hydrolysis of phosphoinositide bisphosphate by PLC. IP3 and DG then act either separately or in concert, via increase of intracellular Ca.sup.2+ and activation of protein kinase C, to regulate the synthesis and release of both luteinizing hormone (LH) and follicle stimulating hormone (FSH). LH released from the pituitary gland is primarily responsible for the regulation of gonadal steroid production in both sexes, whereas FSH regulates spermatogenesis in males and follicle development in females. The GnRH receptor (GnRH-R) is mainly expressed in the pituitary gland. It was also detected in extrapituitary tissues such as brain, breast, gonads, and ovarian tumors. The GnRH receptor has been cloned and sequenced from several mammalian species including human, ovine, bovine, pig, rat, and mouse. The cloning and expression of the murine and human receptors has recently been described in U.S. Pat. No. 5,750,366. The GnRH receptor from bovine, cow, sheep, and human contains 328 amino acids, while the rodent receptor has 327 amino acids, due to a deletion of a residue in the second extracellular domain. Analysis of the primary sequence identifies the GnRH receptor as a member of the G protein-coupled receptor (GPCR) family with seven transmembrane (TM) domains. However, the mammalian GnRH receptors have several unique structural features compared with other GPCRs. These include (1) the lack of the entire intracellular C-terminal tail; (2) the replacement of Tyr by Ser in the conserved G protein signature DRY motif of the proximal second intracellular domain; and (3) the reciprocal exchange of two amino acids, Asp in TM II and Asn in TM VII, that are highly conserved in most other GPCRs. In addition to pituitary gland, the expression of GnRH receptor message has also been demonstrated in extrapituitary tissues such as brain, breast, gonads, and ovarian tumors. The receptor sequences obtained from extrapituitary sources were identical to the corresponding pituitary GnRH receptor cDNAs. Web site: http://www.delphion.com/details?pn=US06407222__

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Combined cryotherapy and hyperthermia method for the treatment of airway obstruction or prostrate enlargement Inventor(s): Beyar; Motti (Herzliya, IL), DeRowe; Ari (Mosahav Salit, IL) Assignee(s): American Medical Systems, Inc. (Minnetonka, MN) Patent Number: 6,378,525 Date filed: January 29, 1998 Abstract: A method of reducing tissue volume for treatment of airway obstruction, obstructive sleep apnea, snoring, prostate tumor, and other pathologies comprising: applying a cryoprobe with a diameter preferably less than about 2 mm and with a sharp tip to first freeze the affected interstitial tissue of the soft palate, base of the tongue, tonsils or adenoids, singularly or in combination, or to the prostate, or other tissue, and then applying the same cryoprobe to heat the treated tissue. Excerpt(s): The present invention relates to a method of reducing tissue volume by applying a unique cryoprobe. The invention is especially useful in reducing pharyngeal tissues, including tonsils and soft palate, in treating upper airway obstruction, such as exists in obstructive sleep apnea, and/or snoring, or in treating an enlarged prostate, and is described below with respect to such applications, but it will be appreciated that the invention could advantageously be used in other applications as well, such as, in treating abundant vascular tissue in the uterus, as found in menometrorrhagia, or in treating hypertrophic inferior turbinates in nasal obstruction. Obstructive Sleep Apnea is of unknown etiology, but it is generally accepted that it results from the combination of a structurally small upper airway and a normal or abnormal loss of physiologic muscle tone during sleep. Patterns of pharyngeal narrowing and collapse suggest that 30-50% of patients with obstructive sleep apnea have obstruction at the level of the upper pharynx or in the retropalatal segment. This can be due to abundant tissue of the palate or tonsillar hypertrophy. An even higher percentage of snorers have the soft palate as the source of the vibrations of snoring. Obstructive Sleep Apnea is a potentially life threatening disorder, which affects up to 2 to 4% of the adult population. Even when not life threatening, it is annoying to a bed mate. Obstructive Sleep Apnea is associated with snoring, which is believed to affect 20% of adults. Web site: http://www.delphion.com/details?pn=US06378525__

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Continuous positive airway pressure headgear Inventor(s): Jestrabek-Hart; Bernadette (Meridian, ID) Assignee(s): Creations by B J H, LLC (Meridian, ID) Patent Number: 6,470,886 Date filed: March 23, 2000 Abstract: The present invention is a CPAP Headgear for assisting in the treatment of sleep apnea. The present invention uses a standard CPAP respiratory mask with air supplied under pressure by an air blower or other source. The present invention generally includes an improved Headgear, preferably having a head cover, a Lip Strap, and Clips and/or Extenders to hold the CPAP respiratory mask in place. The head cover designed with two side portions, each encircling an ear with an open area where the ear will fit and thereby stay a distance from the ear with material that goes upwards toward the top of the head, one side separating into 2 straps that connect across the top of the

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head to the second side. Another strap comes from the back of the left side that encircles the ear and around the nape of the neck to the right side that encircles the right ear, up and through, and back over toward the left, connecting upon itself, thereby connecting the two headpieces together across the nape of the neck. The Lip Strap extends from both lower sides in front of the ears and is attached from one side of the Headgear to the other, and is placed below and on the lower lip cooperating to help keep the wearer's lower lip against the teeth, thereby inhibiting the escape of air from the wearer's mouth, while allowing the chin to relax, and allowing the teeth to be apart as the wearer sleeps. The Clip is a bent hook that attaches to the side strap from the headgear to the respiratory mask attachment and allows the headgear to be removed and replaced easily without losing the adjustments. The Extenders are attachments that are part of a mask or can be or a bent wire attached to an existing respiratory mask. The Extenders drop/lower the attachment where the Headgear is to fasten to the respiratory mask to an area blow the mask. The Extenders primary function is to make the respiratory mask more comfortable to wear, and they may take the place of the Clip. The open Extender allows the Headgear to be removed and replaced easily without losing adjustments. Excerpt(s): The present invention generally relates to medical equipment. More specifically, the present invention relates to headgear used in the treatment of sleep apnea. Sleep apnea is a breathing disorder characterized by brief interruptions of breathing during sleep. Certain mechanical and structural problems in the airway of a person cause the interruptions in breathing during sleep. In some people, apnea occurs when the throat muscles and tongue relax during sleep and partially block the opening of the airway. When the muscles of the soft palate at the base of the tongue and the uvula (the small fleshy tissue hanging from the center of the back of the throat) relax and sag, the airway becomes blocked, making breathing labored and noisy and even stopping it all together. Sleep apnea also can occur in obese people when an excess amount of tissue in the airway causes it to be narrowed. With a narrowed airway, the person continues his or her efforts to breathe, but air cannot easily flow into or out of the nose or mouth. Unknown to the person, this results in heavy snoring, periods of no breathing, and frequent arousals (causing abrupt changes from deep sleep to light sleep). Source: Facts About Sleep Apnea, National Institute of Health, Publication No. 95-3798, September 1995. During the apneic event, the person is unable to breathe in oxygen and to exhale carbon dioxide, resulting in low levels of oxygen and increased levels of carbon dioxide in the blood. The reduction in oxygen and increase in carbon dioxide alert the brain to resume breathing and cause an arousal. With each arousal, a signal is sent from the brain to the upper airway muscles to open the airway; breathing is resumed, often with a loud snort or gasp. Frequent arousals, although necessary for breathing to restart, prevent the patient from getting enough restorative, deep sleep. Id. Web site: http://www.delphion.com/details?pn=US06470886__ •

Determination of Apnea type Inventor(s): Gavriely; Noam (Haifa, IL) Assignee(s): Karmel Medical Acoustic Technologies Ltd. (Yokneam-Illit, IL) Patent Number: 6,375,623 Date filed: October 6, 2000 Abstract: A method of differentiating between OSA and CSA comprising: determining if chest motion above a chest motion threshold is present; determining if tracheal breath sound above a breath sounds threshold are present, classifying a state as OSA if the

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chest motion is above the threshold and the sounds are below the threshold; and classifying a state as CSA if both the chest motion and sounds are below their respective thresholds. Excerpt(s): The present invention relates to the field of determination of breathing disorders and more particularly to the determination of Apnea and Hypopnea and in particular of the type of Apnea. Apnea is defined as cessation of breathing activity for a certain duration (6-20 seconds). Hypopnea is either slow breathing or shallow breathing or both. Detection of apnea/hypopnea (AH) is important in the diagnosis of the sleep apnea syndrome (SAS), a condition that afflicts 2% of adult females and 4% of adult male population in western countries. Detection of AH is also important in the diagnosis of breathing irregularity conditions in children and elderly patients. The diagnosis of SAS is traditionally performed in a sleep lab, but in recent years devices for home analysis of performance have been developed to offset the substantial cost and inconvenience of a full sleep lab study. Detection of AH in a sleeping subject requires identification of actual air flow into and out of the thorax. Thus, mere monitoring of chest motion as performed with impedance pneumography is not sufficient. The existing technology is based on the use of thermal sensors in the nostrils and/or the use of chest and abdomen volume monitors (for example, inductive plethysmography which is available under the trade name Respitrace.TM. These methods either require instrumentation of the patient's face or use of circumferential belts around the chest and abdomen. Both approaches impose substantial inconvenience and are prone to data corruption. Web site: http://www.delphion.com/details?pn=US06375623__ •

Device and method for nonclinical monitoring of breathing during sleep, control of CPAP treatment and preventing apnea Inventor(s): Lynch; Christopher (North Ryde, AU), Sullivan; Colin E. (Birchgrove, AU) Assignee(s): ResMed Limited (North Ryde, AU) Patent Number: 6,398,739 Date filed: August 2, 1999 Abstract: Patient may operate a CPAP system to deliver appropriate airway pressure home. A patient's apnea problem can be diagnosed at home without supervision with a CPAP device which delivers a continuously minimum appropriate pressure for substantially the entire period of therapy. Excerpt(s): A particular application of the present invention is to the diagnosis and/or treatment of snoring and sleep apnea. Sleep apnea is characterized by complete occlusion of the upper airway passage during sleep while snoring is characterized by partial occlusion. Obstructive sleep apnea sufferers repeatedly choke on their tongue and soft palate throughout an entire sleep period resulting in lowered arterial blood oxygen levels and poor quality of sleep. It should be realized that although the following specification discusses sleep apnea in detail, the present invention also applies to the diagnosis and treatment of other forms of upper airway disorders. Reference to international patent publication WO 82/03548 will show that the application of continuous positive airway pressure (CPAP) has been used as a means of treating the occurrence of obstructive sleep apnea. The patient is connected to a positive pressure air supply by means of a nose mask or nasal prongs. The air supply breathed by the patient, is at all times, at slightly greater than atmospheric pressure. For example, gauge

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pressures will typically be within the range of 2 cm to 25 cm. It has been found that the application of continuous positive airway pressure provides what can be described as a "pneumatic splint", supporting and stabilizing the upper airway and thus eliminating the occurrence of upper airway occlusions. It is effective in eliminating both snoring and obstructive sleep apnea and in many cases, is effective in treating central and mixed apnea. The airway pressure required for effective CPAP therapy differs from patient to patient. In order to discover the airway pressure which is most effective for a particular individual, the practice has been for the patient to undergo two sleep studies at an appropriate observation facility such as a hospital, clinic or laboratory. The first night is spent observing the patient in sleep and recording selected parameters such as oxygen saturation, chest wall and abdominal movement, air flow, expired CO.sub.2, ECG, EEG, EMG and eye movement. This information can be interpreted to diagnose the nature of the sleeping disorder and confirm the presence or absence of apnea and where present, the frequency and duration of apneic episodes and extent and duration of associated oxygen desaturation. Apneas can be identified as obstructive, central or mixed. The second night is spent with the patient undergoing nasal CPAP therapy. When apnea is observed the CPAP setting is increased to prevent the apnea. The pressure setting at the end of the sleep period, i.e., the maximum used, is deemed to be the appropriate setting for that patient. For a given patient in a given physical condition there will be found different minimum pressures for various stages of sleep in order to prevent occlusions. Furthermore, these various pressure will, in fact, vary from day to day depending upon the patient's physical condition, for example, nasal congestion, general tiredness, effects of drugs such as alcohol, as well as their sleeping posture. Thus the appropriate pressure found in the laboratory is necessarily the maximum of all these minimum pressures for that particular night and is not necessarily the ideal pressure for all occasions nor for every night. It will generally be higher than necessary for most of the night. Web site: http://www.delphion.com/details?pn=US06398739__ •

ECG derived respiratory rhythms for improved diagnosis of sleep apnea Inventor(s): Bebehani; Khosrow (Arlington, TX), Burk; John R. (Aledo, TX), Lucas; Edgar A. (Fort Worth, TX) Assignee(s): Board of Regents the University of Texas System (Arlington, TX) Patent Number: 6,415,174 Date filed: November 5, 1999 Abstract: Respiratory rhythms of a subject are derived from measured ECG signals utilizing leads placed for significant influence of chest movement on the ECG signals. The QRS pulses within ECG signals measured in two substantially orthogonal planes are located by applying a sequence of filters. The knot and period of the QRS pulses are then determined, with adjustments made during a learning phase of data sampling. The QRS pulse areas in both planes is then calculated. These pulse areas are employed to determine the angle of orientation of the depolarization wave's mean electrical axis (MEA) at the QRS pulse locations. Cubic spline interpolation of the data points for the MEA angle provides a smooth breathing curve, which may be scored for sleep disordered breathing events. The ECG-derived respiratory (EDR) signal may be employed in lieu of airflow measurements where such measurements are not available, or may be employed in conjunction with airflow measurements and/or measured cardiac activity data to discriminate between arrhythmias associated with disordered breathing versus those associated with cardiac malfunction, reducing misdiagnosis. The

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additional processing of ECG data required for derivation of respiratory rhythms may be easily automated and implemented at nominal incremental cost per unit. Excerpt(s): The present invention relates generally to diagnosis of sleep disordered breathing and in particular to diagnosis of sleep disordered breathing utilizing electrocardiographic measurements. Still more particularly, the present invention relates to derivation of respiratory data from electrocardiographic measurements for determining either the presence of sleep disordered breathing causing or aggravating cardiac symptoms or the absence of sleep disordered breathing influence on cardiac symptoms due to cardiac pathology. Sleep disordered breathing is a significant problem for a large portion of the population. Sleep apnea, an intrinsic dyssomnia involving cessation of breathing during sleep and resulting in complete or partial arousal from sleep, is one of the most prevalent forms of sleep disordered breathing. Symptoms of the disorder include daytime sleepiness, fatigue or tiredness, and irritability, which may seriously impair the performance of the individual. Sleep apnea is typically defined as the cessation of air exchange (breathing) from the nostrils or mouth lasting at least 10 seconds. Partial or complete arousal from sleep is considered a defensive mechanism most likely stimulated by rising carbon dioxide levels in the blood during the apneic event to reestablish ventilation and prevent death in the sleeping subject. Three established categorized of sleep apnea include: obstructive sleep apnea, obstruction of the upper airway; central sleep apnea, cessation of ventilatory effort; and mixed apnea, a combination of both upper airway obstruction and cessation of ventilatory effort. Web site: http://www.delphion.com/details?pn=US06415174__ •

Fiber optic monitor using interferometry for detecting vital signs of a patient Inventor(s): Maida, Jr.; John L. (511 Three Corners, Houston, TX 77024), Varshneya; Deepak (3057 Caminito Sagunto, Del Mar, CA 92014-3934) Assignee(s): none reported Patent Number: 6,498,652 Date filed: February 8, 2000 Abstract: A fiber optic monitor that utilizes optical phase interferometry to monitor a patient's vital signs such as respiration, cardiac activity and body's physical movement. The monitor, which is non-invasive, comprises an optical fiber interferometer that includes an optical fiber proximately situated to the patient so that acousto-mechanical signals from the patient are coupled into the optical fiber. Responsive thereto, the interferometer generates a time-varying serial train of fringes which is detected by a photo-detector. A signal processor coupled to the optical detector provides one or more processed output signals indicative of the vital functions. The monitor system has broad applicability, from routine monitoring of infants at home to apnea, arrhythmia and trauma situations. The system can be implemented in embodiments ranging from a low cost in-home monitor for infants to a high end product for in hospital use to monitor infants in nenonatalogy laboratories or at home by physician's prescription. The monitor can be integrated with other sensors such as an EKG, a camera, an oxygen sensor, a carbon-di-oxide sensor, temperature sensor or a microphone to get additional required information depending on the application. When integrated and combined with EKG information, the monitor provides ballisto-mechanical information of the heart for early diagnosis or prediction of cardiac conditions or events. In some embodiments of the monitor, the system can be made portable so that the patient can walk around while still being continuously monitored.

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Excerpt(s): The present invention generally relates to monitors for detecting cardiac and pulmonary motions such as heartbeat, respiration, physical movement, and other body activities of a patient. For detecting vital signs of a patient, there are a number of monitors available with a variety of uses and applications. These vital sign monitors and other advanced monitors range from simple sound monitors such as "baby monitors" used at home, to sophisticated apnea monitors and electro-cardiograms (EKGs) used by physicians and hospitals. Off-the-shelf low cost, non-prescription baby monitors are currently in wide use to monitor infants at home to verify an infant's well-being. These monitors generally employ a microphone sensor that sends a signal to a remote unit with visual and audio displays. For example, the microphone sensor can be placed close to the crib on a table or hooked up to the crib with a bracket while the remote unit is carried around in the house by parent or other caregiver. Although these units are suitable to monitor low risk infants when they are awake and moving around or crying in the crib, they are not reliable for monitoring them during sleep periods. Parents may be concerned that their child is in jeopardy if they can not hear their child's cries or other normal sounds over the monitor. To address this concern, a parent may make many visits to the room where the infant is asleep to either wait patiently until the infant moves in the crib or attempt to touch the infant in an effort to detect child's breathing. Web site: http://www.delphion.com/details?pn=US06498652__ •

Medical equipment warning device Inventor(s): Most, Jr.; Clark (1909 S. Badour Rd., Midland, MI 48640) Assignee(s): none reported Patent Number: 6,392,555 Date filed: November 16, 1999 Abstract: The medical equipment warning device is employed in combination with a power operated medical treatment machine such as a sleep apnea treatment machine. The warning device includes a DC relay with contacts that are open when the relay is connected to an AC source. A signal generator is connected to a battery by the DC relay when the AC source is interrupted and contacts close the DC circuit. The signal generator produces an audible, visual or physical signal that warns a person that the AC power source has failed. Restoration of the AC power source activates the DC relay and opens the DC circuit thereby deactivating the signal generator. Excerpt(s): This invention relates to a medical equipment warning device and more particularly to a warning device that provides an audible warning if a medical device such as a sleep apnea treatment device fails or the devices power source fails. Sleep apnea is a transient cessation of respiration while a person is sleeping. The symptoms are varied and the cause of sleep apnea is unknown. Some individuals with sleep apnea may merely snore. Others reduce air intake and the oxygen level in their hemoglobin decreases. A reduction in hemoglobin oxygen level may be fatal if it is not corrected quickly. Apnea is associated with restriction of the upper passages of the human respiratory system. The methodology for treating sleep apnea is to supply air to the respiratory system under pressure. The air under pressure tends to expand the air passages and thereby increase the flow of oxygen to the lungs. The air under pressure may be supplied by elaborate machines in a hospital for treatment of sleep apnea. The air under pressure may also be supplied to some individuals in their homes any time they sleep. The machines used in hospitals may supply air during inspiration at one pressure and during expiration at a lower pressure. These machines have central

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processing units that sense air flow rates, leakage, pressure, humidity and vibrations due to snoring. The measurements sensed may be recorded in the central processing unit. Some processing units make appropriate adjustments in air flow and pressure after each breath. The recorded measurements and the adjustments help doctors determine future treatment. These elaborate machines are relatively expensive. Individuals that require pressurized air when sleeping use less elaborate machines. Such machines are much less expensive. However, they are modified as required to meet the requirements of each individual with sleep apnea that requires such a machine. Some individuals for example, cannot tolerate pressurized air during expiration. Such individuals require a machine that supplies air at a lower pressure during expiration. Web site: http://www.delphion.com/details?pn=US06392555__ •

Method and apparatus for closed-loop stimulation of the hypoglossal nerve in human patients to treat obstructive sleep apnea Inventor(s): Durand; Dominique (36765 Valley Forge Dr., Solon, OH 44122), Haxhiu; Musa A. (3683 Meadowbrook Blvd., University Heights, OH 44118), Sahin; Mesut (711 S. Vienna, Ruston, LA 71270) Assignee(s): none reported Patent Number: 6,587,725 Date filed: March 26, 2001 Abstract: This invention is a fully implanted functional electrical stimulator (20) apparatus, a method for treatment of obstructive sleep apnea that provides for both reliable detection/prediction or airway occlusion that relieves, and/or prevents same by selective, direct electrical stimulation of the hypoglossal nerve (HG). The method, and apparatus sense hypoglossal nerve electro-neurogram activity for purposes of detecting or predicting obstructive sleep apnea. The sensed hypoglossal nerve activity, itself, is used to trigger functional electrical stimulation of the hypoglossal nerve in order to improve upper airway patency. Further, an improved hypoglossal nerve stimulation electrode (10) interface (IC) is provided that allows for simultaneous hypoglossal nerve activity sensing, and stimulation by eliminating stimulation artifacts that would otherwise trigger further erroneous stimulation. Excerpt(s): The present invention relates generally to the functional electrical stimulation (FES) arts. More particularly, the present invention relates to a method and apparatus for sensing hypoglossal nerve activity in human patients to detect obstructive sleep apnea, and using the sensed hypoglossal nerve activity to trigger selective functional electrical stimulation of the hypoglossal nerve, itself, for purposes of improving upper airway patency and, thus, treating obstructive sleep apnea. Further, the present invention relates to an improved hypoglossal nerve stimulation electrode interface that allows for simultaneous hypoglossal nerve activity sensing and nerve stimulation by eliminating stimulation artifacts that would otherwise trigger further, erroneous stimulation. Obstructive sleep apnea (OSA) is the recurrent occlusion of the upper airways of human patients during sleep. In these patients, the upper airways obstruct as often as several times a minute with each episode lasting as long as 20-30 seconds. Each apneic episode ends with a brief arousal from sleep. Consequently, arterial oxyhemoglobin saturation decreases drastically. Complications include excessive daytime sleepiness, restless sleep, morning headache, job-related accidents, impaired short-term memory, polycythema, hypertension, right-sided congestive heart failure, decreased libido, and the like. Personality disorder and other psychological problems

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may also develop over time. Obstructive sleep apnea is found in 2 to 4 percent of the population, primarily in adult men and post-menopausal women. In humans, the hypoglossal nerve innervates the intrinsic and extrinsic muscles of the tongue and the geniohyoid muscle. Of these muscles innervated by the hypoglossal nerve, the genioglossus and the geniohyoid muscles are the primary muscles involved in dilating the upper airways (UAWS). Contraction of the genioglossus muscle provides tongue protrusion and, hence, dilates the airways. Web site: http://www.delphion.com/details?pn=US06587725__ •

Method and apparatus for diagnosing sleep breathing disorders while a patient in awake Inventor(s): Katz; Richard A. (East Lyme, CT), Lawee; Michael S. (Marblehead, MA), Newman; Anthony Kiefer (Woburn, MA) Assignee(s): The United States of America as represented by the Secretary of the Navy (Washington, DC) Patent Number: 6,580,944 Date filed: November 28, 2000 Abstract: An apparatus and method for identifying the timing of the onset of and duration of an event characteristic of sleep breathing disorder while a patient is awake. Chaotic processing techniques analyze data concerning a cardio-respiratory function, such as nasal air flow. Excursions of the resulting signal beyond a threshold provide markers for delivering the average repetition rate for such events that is useful in the diagnosis of obstructed sleep apnea and other respiratory dysfunctions. Excerpt(s): The invention described herein may be manufactured and used by or for the Government of the United States of America for governmental purposes without the payment of any royalties thereon or therefor. This invention is generally related to methods and apparatus for performing medical diagnoses and particularly to a method and apparatus for enabling the diagnosis of sleep breathing disorders or other physiological respiratory dysfunction while the patient is awake. Sleep breathing disorders and other physiological respiratory dysfunctions in humans constitute an area requiring diagnosis. One such area is called obstructive sleep apnea or sleep disorder breathing. Within the pediatric, infant and newborn population the incidence of apparent life threatening events, sudden infant death syndrome and sleep disorder breathing have all been well documented. Sleep apnea also affects over 25% of apparently healthy adults age 55 and older. Sleep apnea contributes to daytime fatigue, increased work place accidents and a number of cardiovascular disorders. The need for a relatively easily implemented procedure exists to provide efficient methods and procedures for diagnosing these various physiological respiratory dysfunctions. Web site: http://www.delphion.com/details?pn=US06580944__

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Method and combination for treating sleep apnea using a cantilever mask attachment device Inventor(s): Bloom; Nicole Denise (San Francisco, CA), Bordewick; Steven S. (Shoreview, MN), Hansen; Gary L. (Eden Prairie, MN) Assignee(s): Mallinckrodt, Inc. (St. Louis, MO) Patent Number: 6,516,802 Date filed: May 2, 2001 Abstract: A continuous positive airway pressure (CPAP) system in combination with a device for positioning a breathing apparatus over a breathing orifice in the head of a person, the person having an occipital lobe and an axis of symmetry, the device including an occipital anchor for anchoring against the head of the person beneath the occipital lobe of the person. The device further including a forward anchor for anchoring against a forward portion of the person's head. A spring connector connects the forward anchor and the occipital anchor, and biases the occipital anchor against the head of the person beneath the occipital lobe and the forward anchor against the corresponding portion of the person's head so as to attach the device to the person's head. The occipital anchor, the forward anchor and the spring connector are substantially aligned along the axis of symmetry of the person's head. The mount is connected to the spring connector for mounting the apparatus so as to locate the apparatus over the orifice. Excerpt(s): The present invention relates to the field of devices and methods for holding breathing devices and the like in place on a person's head. Breathing devices, such as masks and the like, typically are held in place on a person's face by a harness including one or more straps extending around the person's head and along the side of the person's face. Known devices have a variety of drawbacks. If the strap system is complex, it may not be obvious to the prospective wearer how to properly use the system, and elderly patients may struggle with putting on a mask when help is not present. Web site: http://www.delphion.com/details?pn=US06516802__

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Method for monitoring heart failure via respiratory patterns Inventor(s): Turcott; Robert (Menlo Park, CA) Assignee(s): Pacesetter, Inc. (Sunnyvale, CA) Patent Number: 6,600,949 Date filed: May 5, 2000 Abstract: A method for monitoring the condition of a heart failure patient using respiration patterns is provided. An implantable or other ambulatory monitor senses the patient's respiratory patterns to identify the presence of periodic breathing or CheyneStokes respiration. In a first embodiment, mechanical changes of the thorax due to breathing are detected and this data is used to recognize hyperventilation and apnea or hypoventilation. In a second embodiment of the invention, Cheyne-Stokes respiration is recognized by detecting changes in blood or tissue pH or CO.sub.2 concentration and partial pressure. In another embodiment of the invention, changes in pulse amplitude associated with Cheyne-Stokes respiration are detected. Alternating loss and return of respiration-induced amplitude modulation or pulse-interval variation may also be used

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to identify the presence of Cheyne-Stokes respiration. In yet another embodiment of the invention, modulation of the average heart rate over time is monitored and its absence is used as an indicator of Cheyne-Stokes respiration. This information may be used to warn the patient or healthcare provider of changes in the patient's condition warranting attention. Excerpt(s): This invention relates generally to implantable monitoring devices, and more particularly to a method for monitoring the hemodynamic status of a patient with a chronic disease such as heart failure, ischemic heart disease, or diabetes. Many chronic diseases, such as diabetes and heart failure, require close medical management to reduce morbidity and mortality. Because the disease status evolves with time, frequent physician follow-up examinations are often necessary. At follow-up, the physician may make adjustments to the drug regimen in order to optimize therapy. This conventional approach of periodic follow-up is unsatisfactory for some diseases, such as heart failure, in which acute, life-threatening exacerbations can develop between physician follow-up examinations. It is well know among clinicians that if a developing exacerbation is recognized early, it can be easily and inexpensively terminated, typically with a modest increase in oral diuretic. However, if it develops beyond the initial phase, an acute heart failure exacerbation becomes difficult to control and terminate. Hospitalization in an intensive care unit is often required. It is during an acute exacerbation of heart failure that many patients succumb to the disease. It is often difficult for patients to subjectively recognize a developing exacerbation, despite the presence of numerous physical signs that would allow a physician to readily detect it. This problem is well illustrated by G. Guyatt in his article entitled "A 75-Year-Old Man with Congestive Heart Failure," 1999, JAMA 281(24)2321-2328. Furthermore, since exacerbations typically develop over hours to days, even frequently scheduled routine follow-up with a physician cannot effectively detect most developing exacerbations. It is therefore desirable to have a system that allows the routine, frequent monitoring of patients so that an exacerbation can be recognized early in its course. With the patient and/or physician thus notified by the monitoring system of the need for medical intervention, a developing exacerbation can easily and inexpensively be terminated early in its course. The multiplicity of feedback mechanisms that influence cardiac performance places the heart at the center of a complex control network. The neurohumoral axis includes the autonomic nervous system, consisting of sympathetic and parasympathetic branches, and numerous circulating hormones such as catacholamines, angiotensin, and aldosterone. Neural reflex arcs originating from pressure and stretch receptors, which directly measure mechanical hemodynamic status, modulate the neurohumoral axis. Similarly, chemoreceptors respond to changes in CO2, pH, and O2, which assesses cardiopulmonary function. The neurohumoral system influences cardiac performance at the level of the cardiac electrical system by regulating heart rate and the conduction velocity of electrical depolarizations. It also influences cardiac performance at the mechanical level, by controlling contractility, that is, the effective vigor with which the heart muscle contracts. Conventional cardiac monitors, such as defibrillators, pacemakers, Holter monitors, and cardiac event records, are tailored for the diagnosis and/or therapy of abnormalities of the cardiac electrical system. In contrast, heart failure is a disease of the cardiac mechanical system: it is primarily a failure of the myocardium to meet the mechanical pumping demands required of it. In monitoring the status of a heart failure patient, measuring the mechanical hemodynamic variables is clearly desirable. Examples of mechanical hemodynarnic variables include atrial, ventricular, and arterial pressures, and cardiac output (volume of blood pumped into the aorta per unit time). However, because of the complex feedback network that monitors and controls cardiac performance, measuring variables that do not directly

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reflect the mechanical performance of the heart is also useful. In this way, measuring cardiac electrical activity to assess heart rate variability (described below) allows one to infer the state of the autonomic nervous system, which allows one to infer information about the hemodynamic status of a heart failure patient. Similarly, recognition of Cheyne-Stokes respiration (described below) via respiratory pattern analysis, hemoglobin saturation analysis, and blood gas analysis allows one to detect the presence of pulmonary edema, and thereby detect an acute heart failure exacerbation, though none of these parameters directly measure mechanical hemodynamic status. Web site: http://www.delphion.com/details?pn=US06600949__ •

Method to produce nasal and oral cannula apnea detection devices Inventor(s): Curti; James N. (Bakersfield, CA) Assignee(s): Salter Labs (Arvin, CA) Patent Number: 6,533,983 Date filed: January 4, 2001 Abstract: A method of forming a cannula by forming a cannula mandrel assembly having a nare mandrel, a main body mandrel and mouthpiece mandrel; heating the cannula mandrel assembly, applying a polymeric material to the cannula mandrel assembly to provide a desired material thickness on the mandrel assembly to form the cannula, curing the polymeric material of the formed cannula and extracting the mandrel assembly from the cannula by disassembly and removal of the mandrel assembly parts. Excerpt(s): This invention provides a novel method of producing cannulas suitable for use in both nasal and oral applications, using disconnectable mandrel parts to form the mold over which cannula forming plastics material is applied to form the cannula. This invention relates generally to cannulas adapted for both mouth and nasal use to monitor breathing, in particular, a method of manufacturing a cannula adapted to interconnect with both nasal passages and the mouth for use to monitor breathing, especially for the detection of apnea. Nasal cannulas are commonly used to administer gases, such as oxygen, to humans having respiratory problems. Illustrations of nasal cannulas used for this purpose are found in U.S Pat. No. 3,802,431. Nasal cannulas have been used also for inhalation therapy, made possible by development of inhalation sensors such as described in U.S. Pat. No. 4,745,925. A nasal cannula can be used to monitor breathing and for detection of apnea (the absence of breathing) when connected to an inhalation sensor. Web site: http://www.delphion.com/details?pn=US06533983__

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Methods for treating bulimia using optically pure (-) norcisapride Inventor(s): Barberich; Timothy J. (Concord, MA), Rubin; Paul D. (Sudbury, MA) Assignee(s): Sepracor, Inc. (Marlborough, MA) Patent Number: 6,559,165 Date filed: November 28, 2000 Abstract: Methods for the prevention, treatment, or management of apnea, apnea disorders, bulimia nervosa, irritable bowel syndrome, urinary incontinence,

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bradycardia, bradyarrhythmia, syncope, other disorders, or symptoms thereof using (-) norcisapride, or a pharmaceutically acceptable salt thereof, substantially free of its (+) stereoisomer. Excerpt(s): The invention relates to methods of prevention, treatment, or management, of apnea, apnea disorders, bulimia, other disorders, or symptoms thereof. Apnea is defined in Stedman's Medical Dictionary, 26.sup.th Edition, Williams and Wilkins (1995), as the absence of breathing. There are a number of disorders associated with apnea, which are characterized by interrupted breathing in which a person stops breathing long enough to decrease the amount of oxygen and increase the amount of carbon dioxide in the blood and brain. Each type of apnea involves the absence of airflow at the nose or the mouth, typically for at least 10 seconds. Various apnea disorders exist, including: central apnea, which results from medullary depression and inhibits respiratory movement; deglutition apnea, which is the inhibition of breathing during swallowing; obstructive or peripheral apnea, which is either a result of obstruction of air passages or inadequate respiratory muscle activity; sleep apnea, which is central and/or obstructive apnea during sleep; and sleep induced apnea, which results from failure of the respiratory center to stimulate adequate respiration during sleep. Web site: http://www.delphion.com/details?pn=US06559165__ •

Methods for treating vascular dementia Inventor(s): Pratt; Raymond (Leonia, NJ) Assignee(s): Eisai Co., Ltd. (Tokyo, JP) Patent Number: 6,458,807 Date filed: September 4, 2001 Excerpt(s): The invention describes novel methods for treating and preventing dementia caused by vascular diseases; dementia associated with Parkinson's disease; Lewy Body dementia; AIDS dementia; mild cognitive impairments; age-associated memory impairments; cognitive impairments and/or dementia associated with neurologic and/or psychiatric conditions, including epilepsy, brain tumors, brain lesions, multiple sclerosis, Down's syndrome, Rett's syndrome, progressive supranuclear palsy, frontal lobe syndrome, and schizophrenia and related psychiatric disorders; cognitive impairments caused by traumatic brain injury, post coronary artery by-pass graft surgery, electroconvulsive shock therapy, and chemotherapy, by administering a therapeutically effective amount of at least one of the cholinesterase inhibitor compounds described herein. The invention also describes novel methods for treating and preventing delirium, Tourette's syndrome, myasthenia gravis, attention deficit hyperactivity disorder, autism, dyslexia, mania, depression, apathy, and myopathy associated with or caused by diabetes by administering a therapeutically effective amount of at least one of the cholinesterase inhibitor compounds described herein. The invention also describes novel methods for delaying the onset of Alzheimer's disease, for enhancing cognitive functions, for treating and preventing sleep apnea, for alleviating tobacco withdrawal syndrome, and for treating the dysfunctions of Huntington's Disease by administering a therapeutically effective amount of at least one of the cholinesterase inhibitor compounds described herein. A preferred cholinesterase inhibitor for use in the methods of the invention is donepezil hydrochloride or ARICEPT.RTM. Novel cholinesterase inhibitors are described in U.S. Pat. No. 4,895,841 and WO 98/39000, the disclosures of which are incorporated by reference herein in their

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entirety. The cholinesterase inhibitors described in U.S. Pat. No. 4,895,841 include donepezil hydrochloride or ARICEPT.RTM., which has proven to be a highly successful drug for the treatment of Alzheimer's disease. There is a need in the art for new and improved treatments for other diseases, disorders, and syndromes that are characterized by symptoms of dementia and/or cognitive impairments. The invention is directed to these, as well as other, important ends. Web site: http://www.delphion.com/details?pn=US06458807__ •

Methods of treating respiratory disorders Inventor(s): Deeley; Alan G. (226 W. Boardman St., Youngstown, OH 44503), Knebelman; Stanley (1445 City Line Ave., Wynnewood, PA 19096) Assignee(s): none reported Patent Number: 6,634,353 Date filed: March 17, 2000 Abstract: A method of treating a patient having a malocclusion between the upper and lower mandibles, and obtaining optimum relative positioning of the mandibles. The treatment is useful in correcting respiratory conditions such as sleep apnea, and in prosthodontics and implantology. The method comprises measuring the malocclusion and determining the variation of the malocclusion from an optimal line occlusal contact, then mounting a dental appliance on one or both of the upper and lower mandibles and providing points of engagement on the exposed surface of the appliance to engage the other mandible as it is moved towards the closed position against the one mandible, to thereby reposition the mandibles in a direction toward line occlusion. After one or more periods of use of the appliance, the appliance is modified until the mandibles achieve line occlusion. To reinforce the treatment, at times of repose, the patient's mandibles may be biased toward closure so as to effect relative displacement of the mandibles from the maloccluded positioning toward the nine positioning. Excerpt(s): The present invention relates to the treatment of respiratory disorders and has particular application to effecting a physiological change in the patient to correct the cause of the respiratory disorder. Respiratory disorders occur in patients, resulting in a variety of effects such as sleep apnea, snoring, labored breathing, oxygen starvation, and the resulting physical impairments arising from such disorders. Severe cases of breathing impairment are treated by oxygen therapy. Snoring is treated by various techniques for causing the patient to assume a sleeping position or orientation which avoids or reduces the likelihood of obstruction of the airway which may be the cause of the snoring. Snoring often accompanies an apnea condition in which the patient has repeated episodes of interrupted breathing during sleep. Such interruptions are normally caused by temporary blockage of the airway, for example by reason of lack of muscle tone in the tissue surrounding the airway which allows the tissue to block the airway. Surgical treatment of apnea involves the excision of the tissue causing the blockage and frequently the surgery treatment fails to correct the problem. A more common treatment is the use of continuous positive airway pressure (CPAP). In this treatment, the patient wears a nasal mask which provides a positive airway pressure in the nostrils which splits the airway open and prevents tissue from occluding it. Prescribing the proper level of positive air pressure is accomplished in a sleep laboratory by trial-and-error. Web site: http://www.delphion.com/details?pn=US06634353__

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Oral orthesis to reduce snoring and sleep apnea symptoms Inventor(s): Tielemans; W. M. J. (Maaseik, BE) Assignee(s): TNV Research and Development (NL) Patent Number: 6,408,852 Date filed: January 11, 2001 Abstract: An oral orthesis for reduction of snoring and sleep apnea symptoms. Excerpt(s): The invention relates to an oral orthesis for reducing snoring and sleep apnea symptoms comprising a maxilla pallatum plate (1) and, attached thereon, fixing means (2) to fix the plate in the oral cavity and a tongue positioning device (3). Snoring results from the blocking of the airway by the tongue causing the vibrations when air is passed through. In serious occasions, the blocking can cause a temporary lack of oxygen supply to the brain and unconsciousness which may be life threatening. The disadvantage of the known oral orthesis is that it does not sufficiently prevent the blocking of the airway in all circumstances. The object of the present invention therefor is to provide an improved oral orthesis that better prevents snoring and sleep apnea. This object is achieved, according to the invention, in that the plate 1 extents to cover and support also the soft tissue (1b) of the palate moll. Web site: http://www.delphion.com/details?pn=US06408852__

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Passive apnea monitor Inventor(s): Sullivan; Patrick K. (Honolulu, HI) Assignee(s): Ocean Laboratories, Inc. (Honolulu, HI) Patent Number: 6,375,621 Date filed: December 27, 1994 Abstract: The instrument monitors the acoustic and electromechanical signals of the patient and calculates an energy spectrum periodogram or histogram using time series analysis techniques. The patient lies down on a large piezoelectric film (few microns thick) that has the capability of measuring signals from very high to very low frequencies. The heart and respiration rates as well as obstructive apnea can be observed, detected and measured from the spectral peaks in the resulting energy spectrum. A microcomputing machine provides calculations to determine the energy spectrum and provides for discrimination between noise and a true apnea episode. An alarm calls for assistance in the event of an apnea, including obstructive apnea, or a Sudden Infant Death Syndrome (SIDS) episode. Excerpt(s): An interesting application of the proposed technology, to which the invention relates preferably, but not exclusively, is the detection of apnea, the monitoring of biological functions such as heart rate and respiration rates, as well as obstructive apnea, particularly for infants. The invention relates to a system that uses acoustic and electromechanical transducers, such as a piezoelectric film, to measure biological respirative signals over time. Time series analysis techniques are then applied to the measured signals whereby an energy spectrum (periodogram/histogram) is calculated that identifies the rhythmic and pseudo-rhythmic biological functions such as respiration and heart rate and obstructions in the breathing passage (obstructive apnea.). The apnea monitoring instrument offers researchers, clinicians, parents and other people who are involved in child and adult apnea monitoring an inexpensive way

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to monitor respiration, heart rate and obstructive apnea without the use of restrictive electrical wiring. It makes available a low cost monitoring instrument to be used as a highly reliable tool for researching and monitoring Sudden Infant Death Syndrome (SIDS). Web site: http://www.delphion.com/details?pn=US06375621__ •

Physiological stress detector device and method Inventor(s): Sarussi; Israel (Hof Aza, IL) Assignee(s): S.P.O. Medical Equipment Ltd. (Neve Dekalim, IL) Patent Number: 6,553,242 Date filed: February 1, 2000 Abstract: A method and device for measurement of a level of at least one blood constituent. The device includes a light source and a light detector proximate the surface of an organ. The device also includes a pair of adjustable gain amplifiers and a processor/controller connected within a processing unit. The processing unit operates to separate an AC signal component from a DC signal component. The light source includes at least one light emitting unit. Preferably, the light source alternatingly emits light at two different wavelength ranges and normalizes the AC and DC output signals corresponding with the intensity of the light reflected from the organ and calculates a ratio of the normalized signals for each wavelength range. The device may determine the level of the blood constituent and may also use this level for monitoring and/or to activate an alarm when the level falls outside a predetermined range. The device and the method may be applied to monitoring, inter alia, conditions of apnea, respiratory stress, reduced blood flow in organ regions, heart rate, jaundice, and blood flow velocity. Excerpt(s): The present invention relates to instruments which operate on the principle of pulse oximetry, in particular, to non-invasive hemoglobin saturation detectors and methods, and may be generally applied to other electro-optical methods of measuring blood constituents. Electro-optical measurement of blood characteristics has been found to be useful in many areas of blood constituent diagnostics, such as glucose levels, oxygen saturation, hematocrit, billirubin and others. This method is advantageous in that it can be performed in a non-invasive fashion. In particular, much research has been done on oximetry, a way of measuring oxygen saturation in the blood, as an early indicator of respiratory distress. Infants during the first year of life are susceptible to breathing disturbances (apnea) and respiratory distress. Sudden Infant Death Syndrome (SIDS) is a medical condition in which an infant enters respiratory distress and stops breathing, leading to the death of the infant. Although the cause and warning signs of SIDS are not clear, it has been shown that early detection of respiratory distress can provide the time to administer the aid necessary to prevent death. Web site: http://www.delphion.com/details?pn=US06553242__

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Respiratory disease monitoring system Inventor(s): Nishida; Yoshifumi (Tsukuba, JP), Yanai; Kenichi (Nisshin, JP), Yoshimi; Tomohisa (Gamagori, JP) Assignee(s): Denso Corporation (Kariya, JP) Patent Number: 6,450,957 Date filed: July 7, 2000 Abstract: A respiration monitoring system monitors the state of disorder of the respiratory system of a sleeping patient based on the detection of respiratory body movement without the need of putting sensors directly on the patient's body. The system includes weight sensors that produce weight signals attributable to the patient's respiratory body movement. From weight signals having a frequency band of respiration, a respiratory body movement signal is produced, and the fall of blood oxygen saturation which occurs at obstructive apnea of the sleeping patient is determined based on the variation pattern of the amplitude of respiratory body movement signal. The occurrence and frequency of the fall of blood oxygen saturation are displayed on a display unit. Excerpt(s): The present invention relates to a respiration monitoring system, and more particularly to a respiration monitoring system capable of monitoring the state of disorder of the patient's respiratory system during sleep. The recorded data is sent by off-line transfer from the data recorder 106 to an external data analyzer 107, by which the data is analyzed for the diagnosis of respiratory disease. In the diagnostic procedure, the distribution of blood oxygen saturation is first examined, and if a disease is suspected, the patient undergoes more precise inspections based on the data provided by the remaining sensors. It is therefore an object of the present invention to provide a respiration monitoring system which is capable of monitoring the state of disorder of the patient's respiratory system during sleep based on detecting body movement caused by respiration, and without requiring the sensors to be placed directly on the patient's body. Web site: http://www.delphion.com/details?pn=US06450957__

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Sleep apnea detection system and method Inventor(s): Greene; Leonard M. (White Plains, NY) Assignee(s): Safe Flight Instrument Corporation (White Plains, NY) Patent Number: 6,454,724 Date filed: October 25, 2000 Abstract: An apnea monitor and alarm for monitoring the breathing of an individual and for sounding an alarm in response to an interruption in the cyclical rhythm of breathing is disclosed. The monitor and alarm includes a respiration detector, an alarm and a signal processor and analyzer. The signal processor and analyzer is programmed to arm the alarm after a preselected time of cyclical breathing. The signal processor and analyzer is also programmed to sense an interruption in the breathing cycle and to actuate the alarm after a preselected period of interrupted breathing. The monitor and alarm may also include a deactivation system that recycles the program back to an initial part of the program so that the alarm is once again armed after a preselected time of continuous breathing.

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Excerpt(s): The invention relates to a sleep apnea detection system and method for detecting apnea and respiratory arrest and more particularly to systems wherein a detector is used in conjunction with an alarm to wake an individual or to summon help to restore a normal an breathing cycle. Breathing is normally characterized by a regular rhythm of inhaling and exhaling. However, in many individuals apnea or cessation of respiratory airflow causes an interruption in the breathing cycle which can be hazardous to an individual's health. At times such interruption may result in a complete arrest of breathing. Apnea may be caused by a number of different mechanisms including obstructive episodes in upper airway, by neurologic or disease-medicated lack of diaphragmatic motion, and by a combination of these factors. Some individuals are particularly vulnerable to apnea after general anesthesia. Others receiving epidural narcotics and local anesthetics are at an increased risk of apnea and respiratory arrest. Web site: http://www.delphion.com/details?pn=US06454724__ •

Sleep apnea treatment apparatus Inventor(s): Cattano; Janice M. (Gibsonia, PA), Estes; Mark C. (Irwin, PA) Assignee(s): Respironics, Inc. (Pittsburgh, PA) Patent Number: 6,427,689 Date filed: May 4, 1993 Abstract: Improved methodology and apparatus for the treatment of sleep apnea through (1) application of alternating high and low level positive airway pressure within the airway of the patient with the high and low airway pressure being coordinated with the spontaneous respiration of the patient, (2) usage of adjustably programmable pressure ramp circuitry capable of producing multiple pressure ramp cycles of predetermined duration and pattern whereby the ramp cycles may be customized to accommodate the specific needs of an individual sleep apnea patient so as to ease the patient's transition from wakefulness to sleep, and (3) remote control operation of the apparatus for assisting those patients whose mobility or capacity for physical exertion is intrinsically limited. Excerpt(s): The present invention relates generally to methodology and apparatus for treatment to sleep apnea and, more particularly, to mono-level, bi-level, or proportional assist ventilation (PAV) continuous positive airway pressure (CPAP) apparatus including circuitry for enabling a patient to selectively actuate one or more pressure ramp cycles wherein, during each ramp cycle, available airway pressure increases with time from a predetermined minimum pressure value to a prescription pressure, thereby facilitating the patient's transition from a waking to a sleeping state. The sleep apnea syndrome afflicts an estimated 1% to 3% of the general population and is due to episodic upper airway obstruction during sleep. Those afflicted with sleep apnea experience sleep fragmentation and intermittent, complete or nearly complete cessation of ventilation during sleep with potentially severe degrees of oxyhemoglobin unsaturation. These features may be translated clinically into debilitating daytime sleepiness, cardiac dysrhythmias, pulmonary-artery hypertension, congestive heart failure and cognitive dysfunction. Other sequelae of sleep apnea include right ventricular dysfunction with cor pulmonale, carbon dioxide retention during wakefulness as well as during sleep, and continuous reduced arterial oxygen tension. Hypersomnolent sleep apnea patients may be at risk for excessive mortality from these factors as well as by an elevated risk for accidents while driving and/or operating potentially dangerous equipment. Although details of the pathogenesis of upper airway

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obstruction in sleep apnea patients have not been fully defined, it is generally accepted that the mechanism includes either anatomic or functional abnormalities of the upper airway which result in increased air flow resistance. Such abnormalities may include narrowing of the upper airway due to suction forces evolved during inspiration, the effect of gravity pulling the tongue back to appose the pharyngeal wall, and/or insufficient muscle tone in the upper airway dilator muscles. It has also been hypothesized that a mechanism responsible for the known association between obesity and sleep apnea is excessive soft tissue in the anterior and lateral neck which applies sufficient pressure on internal structures to narrow the airway. Web site: http://www.delphion.com/details?pn=US06427689__ •

System and method for monitoring and controlling a plurality of polysomnographic devices Inventor(s): Berquin; Yves (Brussels, BE), Haberland; Ben (Palm City, FL), Michel; Didier (Linkebeek, BE) Assignee(s): Respironics, Inc. (Pittsburgh, PA) Patent Number: 6,425,861 Date filed: December 3, 1999 Abstract: A polysomnographic system is provided for use in conjunction with a communications network to simultaneously perform sleep studies on a plurality of patients. The polysomnographic system includes a first remote polysomnographic unit for collecting physiological data from a first patient and a second remote polysomnographic unit for collecting physiological data from a second patient. The first and second remote polysomnographic units communicate with a host unit which allows for remote observation and manipulation of sensors and therapeutic devices unit via a communication network. An affiliated pressure support device is controlled if obstructive sleep apnea is present. Excerpt(s): This invention generally relates to a method and apparatus for monitoring and treating sleep disorders, and, more particularly, to a computerized polysomnographic system for simultaneously monitoring a plurality of patients undergoing respective sleep studies and for controlling a pressure support device for each individual patient, either treating a patient or for determining a prescription for treatment of a patient having a breathing disorder, such as sleep apnea. There are three recognized types of sleep apnea. Central sleep apnea is characterized by the suspension of all respiratory movement and is generally believed to be neurological in origin. Obstructive sleep apnea is characterized by the collapse of the upper airways during sleep. The third type of sleep apnea is a combination of central and obstructive sleep apnea and is known as mixed apnea. Individuals having sleep apnea often are only able to sleep for short periods of time before interruption by apneic episodes and, therefore, are only able to obtain fragmented and intermittent sleep. As a result, sleep apnea can cause a host of secondary symptoms, such as general fatigue and daytime sleepiness, high blood pressure, cognitive dysfunction, cardiac arrhythmia, and even congestive heart failure. It is estimated that between 1% and 5% of the general population are afflicted with some level of sleep apnea. Treatments for sleep apnea have included a number of pharmacological agents and several surgical procedures such as tracheostomy or the removal of excess muscle and tissue from the tongue or airway walls. However, pharmacological treatments for sleep apnea have been generally ineffective and may have adverse side effects. Furthermore, the surgical procedures

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involve major surgery which may cause extreme discomfort and may involve significant risk of postoperative complications. Web site: http://www.delphion.com/details?pn=US06425861__ •

Ventilation interface for sleep apnea therapy Inventor(s): Wood; Thomas J. (Waycross, GA) Assignee(s): Innomed Technologies, Inc. (Boca Raton, FL) Patent Number: 6,595,215 Date filed: January 15, 2002 Abstract: The ventilation interface for sleep apnea therapy interfaces a ventilation device to the patient's airways. The ventilation interface includes a pair of nasal inserts made from flexible, resilient silicone which are oval shaped in cross-section and slightly tapered from a base proximal the ventilation supply to the distal tip end. A bead flange is disposed about the exterior of each insert at the distal end of the insert. A bleed port for release of exhaled air is defined through a conical vent projecting normally to the path of the incoming air flow, and continues through a nipple extending to the exterior of the air conduit. In one embodiment, a pair of nasal inserts are integral with a nasal cannula body, with bleed ports axially aligned with each insert. In another embodiment, each insert is independently connected to a separate, thin-walled, flexible supply line. Excerpt(s): The present invention relates to ventilation devices, and particularly to a ventilation device having a nasal inserts which are inserted into the nostrils and seal against the nostrils without the aid of harnesses, head straps, adhesive tape or other external devices, and having exhalation ports designed to eliminate whistling noises, the ventilation interface having particular utility in various modes of therapy for obstructive sleep apnea. Sleep apnea is a potentially lethal affliction in which breathing stops recurrently during sleep. Sleep apnea may be of the obstructive type (sometimes known as the pickwickian syndrome) in which the upper airway is blocked in spite of airflow drive; the central type with decreased respiratory drive; or a mixed type. Breathing may cease for periods long enough to cause or to exacerbate cardiac conditions, and may be accompanied by swallowing of the tongue. Sleep apnea frequently results in fitful periods of both day and night sleeping with drowsiness and exhaustion, leaving the patient physically and mentally debilitated. In recent years it has been found that various forms of positive airway pressure during sleep can be an effective form of therapy for the apnea sufferer. Ventilation can be applied in the form of Continuous Positive Airway Pressure (CPAP) in which a positive pressure is maintained in the airway throughout the respiratory cycle, Bilevel Positive Airway Pressure (BiPAP) in which positive pressure is maintained during inspiration but reduced during expiration, and Intermittent Mechanical Positive Pressure Ventilation in which pressure is applied when an episode of apnea is sensed. Positive airway pressure devices have traditionally employed either a face mask which only covers the patient's nose, or nasal pillows as the interface between the ventilation device and the patient's airway. However, there are problems with both of these interfaces. Web site: http://www.delphion.com/details?pn=US06595215__

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Patent Applications on Apnea 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 apnea: •

Active medical device for the diagnosis of the sleep apnea syndrome Inventor(s): Poezevera, Yann; (Courcouronne, FR) Correspondence: Robert M. Isackson, Esq.; ORRICK, HERRINGTON & SUTCLIFFE LLP; 666 Fifth Avenue; New York; NY; 10103-0001; US Patent Application Number: 20030130589 Date filed: December 16, 2002 Abstract: An active medical device have an improved diagnosis of a sleep apnea syndrome. This device measures the respiratory activity of the patient, determines a state of activity, this state being likely to take, according to satisfaction of predetermined criteria, a value representative of a state of sleep of the patient, and analyzes a detected signal corresponding to the respiratory activity to detect, when the aforementioned state is a state of sleep, the presence of respiratory pauses, and thereby to produce an indicating signal of sleep apnea in the event of the occurrence of a respiratory pause of duration longer than a first predetermined duration. The analysis also includes inhibiting the production of the aforesaid indicating signal, or a treatment to resolve an apnea, when the duration of the detected respiratory pause is longer than a second predetermined duration, typically of at least one minute. Excerpt(s): The present invention relates to the diagnosis of the respiratory disorders, more particularly the diagnosis of the sleep apnea syndrome. The sleep apnea syndrome (SAS), more precisely the syndrome of obstructive apnea of sleep (SOAS) (as contrasted with the syndrome of central sleep apnea) is an affection generally caused by an obstruction of the respiratory tracts. It is susceptible to cause a certain number of disorders such as painful and insufficient breathing, heartbeat disturbance, and hypertension. Various treatments of SOAS have been proposed including, for example, surgery, medications or maintenance of a positive pressure in the respiratory tracts by means of a facial mask applied during the sleep. It also has been proposed to treat SAS by neuro-muscular electric stimulation of the muscles controlling the air routes of the patient, as described in the U.S. Pat. No. 5,485,851 (to Medtronic, Inc.), and, more recently, by a particular stimulation of the myocardium (the so-called "electro-cardiac" stimulation) in the event of a detected SAS, as described, for example, in the U.S. Pat. No. 6,126,611 (to Medtronic, Inc.) and European patent application EO-A-0 970 713 and its corresponding U.S. patent application No.______ (attorney docket no. 8707.2148; 152 Detection Sommeil) (to Ela Mdical). EP-A-0 970 713 (and U.S. application______) has the advantage of operating a discrimination between phases of awakening and sleep, in order to apply a therapy only during a phase of sleep, and to inhibit any treatment if the detected apnea occurs during a phase of awakening, because in this case it is normally not a pathological affection. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

10

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

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•

Adenosine derivatives Inventor(s): Bays, David Edmund; (Ware, GB), Cousins, Richard Peter Charles; (Stevenage, GB), Dyke, Hazel Joan; (Cambridge, GB), Eldred, Colin David; (Stevenage, GB), Judkins, Brian David; (Stevenage, GB), Pass, Martin; (Macclesfield, GB), Pennell, Andrew Michael Kenneth; (San Carlos, CA) Correspondence: BACON & THOMAS, PLLC; 625 SLATERS LANE; FOURTH FLOOR; ALEXANDRIA; VA; 22314 Patent Application Number: 20030096788 Date filed: August 13, 2002 Abstract: A method of treating a patient suffering from or susceptible to ischemic heart disease, peripheral vascular disease or stroke or which subject is suffering pain, a CNS disorder or sleep apnea which comprises administering a therapeutically effective amount of an adenosine derivative which is an agonist at the adenosine A1 receptor and which exhibits little or no agonist activity of the A3 receptor. The adenosine derivative has a general formula (I) as follows: 1 Excerpt(s): The present invention relates to novel adenosine derivatives, to processes for their preparation, to pharmaceutical compositions containing them and to their use in medicine. Publications in this area include WO 98/16539 (Novo Nordisk A/S) which describes adenosine derivatives for the treatment of myocardial and cerebral ischaemia and epilepsy; WO 98/04126 (Rhone-Poulenc Rorer Pharmaceuticals Inc.) which relates to adenosine derivatives possessing antihypertensive, cardioprotective, anti-ischaemic and antilipolytic properties; and WO 98/01459 (Novo Nordisk A/S) which describes N,9-disubstituted adenine derivatives which are substituted in the 4' position by unsubstituted oxazolyl or isoxazolyl and the use of such compounds for the treatment of disorders involving cytokines in humans. R.sup.3 represents H, phenyl (optionally substituted by halogen), a 5 or 6 membered heteroaryl group, C.sub.1-6 alkoxy, C.sub.16 alkylO(CH.sub.2).sub.n where n is 0-6, C.sub.3-7 cycloalkyl, C.sub.1-6 hydroxyalkyl, halogen or a C.sub.1-6 straight or branched alkyl, C.sub.1-6 alkenyl or C.sub.1-6 alkynyl group optionally substituted by one or more halogens. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Administration of CPAP treatment pressure in presence of apnea Inventor(s): Berthon-Jones, Michael; (New South Wales, AU), Farrugia, Steven Paul; (New South Wales, AU) Correspondence: GOTTLIEB RACKMAN & REISMAN PC; 270 MADISON AVENUE; 8TH FLOOR; NEW YORK; NY; 100160601 Patent Application Number: 20030062044 Date filed: October 28, 2002 Abstract: CPAP treatment apparatus is disclosed having a controllable flow generator (34, 38, 40) operable to produce breathable gas at a treatment pressure elevated above atmosphere to a patient by a delivery tube (32) coupled to a mask (30) having connection with a patient's airway. A sensor (44, 50, 56, 58) generates a signal representative of patient respiratory flow, that is provided to a controller (54, 62, 64). The controller (54, 62, 64) is operable to determine the occurrence of an apnea from a reduction in respiratory airflow below a threshold, and if an apnea has occurred, to

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determine the duration of the apnea and to cause the flow generator (34, 38) to increase the treatment pressure. In one preferred form the increase in pressure is zero if the treatment pressure before the apnea exceeds a pressure threshold. Below the pressure threshold the increase in pressure is an increasing function of the duration of the apnea multiplied by the difference between the pressure threshold and the current treatment pressure. Excerpt(s): This application is a Continuation-in-part of co-pending U.S. application Ser. No. 09/008,743, entitled "Administration of CPAP Treatment Pressure in Presence of Apnea" filed Jan. 19, 1998. This invention relates to the administration of continuous positive airway pressure (CPAP) treatment for partial or complete upper airway obstruction. In the Sleep Apnea syndrome a person stops breathing during sleep. Cessation of airflow for more than 10 seconds is called an "apnea". Apneas lead to decreased blood oxygenation and thus to disruption of sleep. Apneas are traditionally (but confusingly) categorized as either central, where there is no respiratory effort, or obstructive, where there is respiratory effort. With some central apneas, the airway is open, and the subject is merely not attempting to breathe. Conversely, with other central apneas and all obstructive apneas, the airway is closed. The occlusion is usually at the level of the tongue or soft palate. The airway may also be partially obstructed (i.e., narrowed or partially patent). This also leads to decreased ventilation (hypopnea), decreased blood oxygenation and disturbed sleep. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Alkylaryl polyether alcohol polymers for treatment and prophylaxis of snoring, sleep apnea, sudden infant death syndrome and for improvement of nasal breathing Inventor(s): Hofmann, Thomas; (Seattle, WA) Correspondence: HANA VERNY; PETERS, VERNY, JONES & SCHMITT, LLP; SUITE 6; 385 SHERMAN AVENUE; PALO ALTO; CA; 94306; US Patent Application Number: 20030053956 Date filed: January 23, 2002 Abstract: A method and composition for treatment and prophylaxis of snoring, sleep apnea or sudden infant death syndrome and for improvement of nasal breathing in mammals by nasal and/or pharyngeal administration of tyloxapol or a related alkylaryl polyether alcohol polymer. A spray, liquid or solid composition comprising from about 0.01 to about 20% (w/v), equivalent to about 100.mu.g/ml to about 200 mg/ml, of tyloxapol or another alkylaryl polyether alcohol polymer alone or in admixture with pharmaceutically acceptable excipients and additives. The composition is administered as a spray, liquid, liquid drops, lozenges or powder suitable for nasal and/or pharyngeal application. Excerpt(s): This application is based on and claims priority of the provisional application Ser. No. 60/264,166 filed on Jan. 24, 2001. The current invention concerns a method and composition for treatment and prophylaxis of snoring, sleep apnea or sudden infant death syndrome and for improvement of nasal breathing in mammals by nasal and/or pharyngeal administration of tyloxapol or a related alkylaryl polyether alcohol polymer. In particular, the present invention provides a spray, liquid or solid composition comprising from about 0.01 to about 20% (w/v), equivalent to about 100.mu.g/ml to about 200 mg/ml, of tyloxapol or another selected alkylaryl polyether alcohol polymer alone, in combination, or in admixture with pharmaceutically

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acceptable excipients and additives. The composition is administered as a spray, liquid, liquid drops, lozenges or powder suitable for nasal and/or pharyngeal application. Snoring and related sleep apnea are amongst the most troublesome sleeping impairments. Snoring is not only a nuisance for other people, but it has been shown, similarly to sleep apnea, to correlate with increased daytime sleepiness and decreased alertness and work performance. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Analysis of sleep apnea Inventor(s): Sheldon, Stephen H.; (Chicago, IL) Correspondence: JAECKLE FLEISCHMANN & MUGEL, LLP; 39 State Street; Rochester; NY; 14614-1310; US Patent Application Number: 20030139680 Date filed: January 22, 2003 Abstract: A non-intrusive and quantitative method and apparatus for diagnosing sleep apnea and detecting apnea events by monitoring during sleep abdominal effort and thoracic effort, determining the phase of each effort, determining the difference in phase between each type of effort, and then determining the rate of phase angle change and standard deviation over time. Also provided may be treatment when apnea events are detected to trigger therapy apparatus such as airway positive pressure apparatus. Excerpt(s): This application claims the benefit of U.S. Provisional Application Ser. No. 60/350,770, filed Jan. 22, 2002. Obstructive Sleep Apnea one of the most common disorders in the U.S. Lower oxygen levels associated with Obstructive Sleep Apnea (OSA) is now known to be a major cause of cardiovascular morbidity including heart attack and stroke. At present expensive polysomnography is used to identify these patients but not on a sufficient scale to provide diagnosis as a practical matter. The development of a diagnostic system which can allow simplified diagnosis of obstructive sleep apnea by the primary care physician would be a major step. The prevention of hundreds of thousands of annual excess deaths, stroke and heart attacks associated with obstructive sleep apnea through simplified recognition of this disorder is the most important purpose of the present invention. These excess deaths are occurring annually in a great part due to the lack of availability of this technology resulting in a vast pool of undiagnosed cases of Sleep Apnea and other breathing disorders. Despite the fact that obstructive sleep apnea is easily treated, both the patient and the family are often completely unaware of the presence of this dangerous disease, thinking the patient just a "heavy snorer". Obstructive sleep apnea often develops insidiously as a patient enters middle age and begins to snore. The major cause is an increase in fat deposition (often age related) in the neck which results in narrowing of the airway. (In fact the probability that a 40 year Id has sleep apnea is directly related to his or her neck circumference). When the muscle tone of the upper airway diminishes during sleep coupled with negative pressure associated with inspiration through this somewhat narrow airway results in collapse of the upper airway in a manner analogous to the collapse of a cellophane straw. This results in airway obstruction and, effectively chokes off all air movement The choking patient (still asleep) begins to struggle and inhales more forcibly, thereby, further lowering upper airway pressure and causing further collapse of the upper airway. During this time, substantially no air movement into the chest occurs and the patient experiences a progressive fall in oxygen (similar to the fall occurring early in drowning). The fall in oxygen produces central nervous system

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stimulation contributing to hypertension and potential heart and blood vessel injury and finally results in arousal. Upon arousal, increase in airway muscle tone opens the airway and the patient rapidly inhales and ventilates quickly to correct the low oxygen levels. Generally, the arousal is brief and the patient is not aware of the arousal (or of the choking since this occurs during sleep). Once oxygen levels have been restored, the patient begins again to sleep more deeply, upper airway tone again diminishes, the upper airway collapses and the cycle is repeated stressing the heart with low oxygen in a repetitive fashion. Often this repeating cycle over many years eventually results in damage to the heart muscle and/or the coronary arteries. As the patient ages, the consequences of undiagnosed obstructive sleep apnea is often either a progressive decline in heart muscle function (and eventual heart failure) or heart infarction. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Apparatus for detecting sleep apnea using electrocardiogram signals Inventor(s): Chazal, Phillip de; (Sutton, AU), Heneghan, Conor; (Dublin, IE), sheridan, Elaine; (Crossdoney, IE) Correspondence: Patrick R. Scanlon; Pierce Atwood; One Monument Square; Portland; ME; 04101; US Patent Application Number: 20030055348 Date filed: September 14, 2001 Abstract: There is provided a method of determining a diagnostic measure of sleep apnea including the following steps: acquiring an electrocardiogram signal, calculating a set of RR intervals and electrocardiogram-derived respiratory signal from said electrocardiogram, and hence calculating a set of spectral and time-domain measurements over time periods including power spectral density, mean, and standard deviation. These measurements are processed by a classifier model which has been trained on a pre-existing data base of electrocardiogram signals to provide a probability of a specific time period containing apneic episodes or otherwise. These probabilities can be combined to form an overall diagnostic measure. The system also provides a system and apparatus for providing a diagnostic measure of sleep apnea. Excerpt(s): This invention relates to cardio-respiratory monitoring and analysis, and more particularly to methods for diagnosing sleep disorders. More specifically, the present invention is aimed at detection of sleep apnea using the electrocardiogram. The invention can be embodied in a form suitable for use in a dedicated medical setting, or in the home. Sleep apnea is a significant public health problem. Current estimates are that approximately 4% of the male middle-aged population, and 2% of the female middle-aged population suffer from sleep apnea. Patients suffering from sleep apnea are more prone to hypertension, heart disease, stroke, and irregular heart rhythms. Continued interruption of quality sleep is also associated with depression, irritability, loss of memory, lack of energy, and a higher risk of car and workplace accidents. Current techniques for detection and diagnosis of sleep apnea rely upon hospital-based polysomnography. A polysomnogram simultaneously records multiple physiologic signals from the sleeping patient. A typical polysomnogram includes measurements of blood oxygen saturation level, blood pressure, electroencephalogram, electrocardiogram, electrooculogram, electromyogram, nasal and/or oral airflow chest effort, and abdominal effort. Typically, signals are recorded from a full night's sleep and then a diagnosis is reached following a clinical review of recorded signals. In some patients a second night's recording is required. Because of the number and variety of

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measurements made, this test can be uncomfortable for the patient and also has a relatively high cost. In general, it is only performed in a dedicated medical facility. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Automatic slope adjustment for bi-levelpressure support system Inventor(s): Yurko, Gregory; (Murrysville, PA) Correspondence: MICHAEL W. HAAS, INTELLECTUAL PROPERTY COUNSEL; RESPIRONICS, INC.; 1010 MURRY RIDGE LANE; MURRYSVILLE; PA; 15668; US Patent Application Number: 20030127097 Date filed: February 19, 2003 Abstract: An apparatus and method for a bi-level positive airway pressure support in which the rise time from the expiratory positive airway pressure to the inspiratory positive airway pressure is automatically controlled by the pressure support system. The pressure support system includes a sensor, a control system, and a pressure generating system. The sensor monitors the patient's respiration to detect respiratory events, such as an apnea, hyponea or other disturbance, and the control system responds to the sensor information to adjust the rise time from the expiratory positive airway pressure to the inspiratory positive airway pressure gas pressure to maximize patient comfort and pressure support treatment effectiveness. Excerpt(s): The present invention claims priority under 35 U.S.C.sctn. 119(e) from U.S. provisional patent application No. 60/216,999 filed Jul. 10, 2000. The present invention generally relates to a bi-level positive airway pressure support system, and, more particularly, to a bi-level pressure support system and method of providing bi-level pressure support in which the rise time from the expiratory phase of pressure support to the inspiratory phase is automatically adjusted. Pressure support systems that provide a flow of breathing to an airway of a patient at an elevated pressure to treat a medical disorder are well known. One basic form of pressure support system is a continuous positive airway pressure (CPAP) system, which typically involves providing a flow of breathing gas, such as air, to a patient's airway at a constant pressure throughout a patient's breathing cycle. When used to treat obstructive sleep apnea (OSA), for example, this constant pressure is provided at a level sufficient to overcome a patient's airway resistances. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

BI/PAP mask for sleep apnea and other related clinical uses Inventor(s): Moone, Samuel Joseph; (Pickerington, OH) Correspondence: Samuel Joseph Moone; 13450 Falmouth Ave.; Pickerington; OH; 43147; US Patent Application Number: 20020144684 Date filed: April 6, 2001 Abstract: The introduction of gas/air flow tubes molded/inserted from the top gas/air flow channel to the front area below the nasal area will generate additional air flow to the user's nose below the nasal openings. The gas/air flow tubes will allow users of breathing masks to become accustomed to masks that will be providing gas/air for

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various purposes. In this instance the mask will be providing comforting simulated breathing for a BIPAP user with sleep apnea, eliminating the feeling of insufficient airflow to the nasal area. This will eliminate user discomfort with current masks that cause discontinued cooperation by patients with the sleeping regimen. By inserting a plug in the bottom of the gas/air flow tube top the mask will convert from a BIPAP mask, to a CPaP mask. This mask can be used in a variety of hospital/healthcare settings where gas/air is used by patients. Excerpt(s): A variety of respiratory masks are known which have flexible seals that cover the nose and/or mouth of a human user and are designed to create a continuous seal against the user's face. Because of the sealing effect that is created, the user may provide gases/air at a positive/simulated breathing pressure within the mask for consumption. The uses for such a mask would range from high altitude breathing (i.e., aviation applications) to mining and fire fighting applications, to various medical diagnostic and therapeutic applications. One requisite of such respiratory masks has been that they provide an effective seal against the user's face to prevent leakage of the gas/air being supplied. Commonly, in mask configurations, a good mask-to-face seal has been attained in many instances only with considerable discomfort for the user. This problem is most crucial in those applications, especially medical applications, which require the user to wear such a mask continuously for hours or perhaps even days. In such situations, the user will not tolerate the mask for long duration's and optimum therapeutic or diagnostic objectives thus will not be achieved, or will be achieved with great difficulty and considerable user discomfort. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Breathing gas delivery method and apparatus Inventor(s): Estes, Mark; (Sylmar, CA), Sanders, Mark H.; (Wexford, PA), Zdrojkowski, Ronald J.; (Pittsburgh, PA) Correspondence: MICHAEL W. HAAS, INTELLECTUAL PROPERTY COUNSEL; RESPIRONICS, INC.; 1010 MURRY RIDGE LANE; MURRYSVILLE; PA; 15668; US Patent Application Number: 20030145856 Date filed: March 3, 2003 Abstract: An improved methodology and systems for delivery of breathing gas such as for the treatment of obstructive sleep apnea through application of alternating high and low level positive airway pressure within the airway of the patient with the high and low airway pressure being coordinated with the spontaneous respiration of the patient, and improved methods and apparatus for triggering and for leak management in such systems. Excerpt(s): The sleep apnea syndrome, and in particular obstructive sleep apnea, afflicts an estimated 4% to 9% of the general population and i due to episodic upper airway obstruction during sleep. Those afflicted with obstructive sleep apnea experience sleep fragmentation and intermittent, complete or nearly complete cessation of ventilation during sleep with potentially severe degrees of oxyhemoglobin unsaturation. These features may be translated clinically into debilitating daytime sleepiness, cardiac disrhythmias, pulmonary-artery hypertension, congestive heart failure and cognitive dysfunction. Other sequelae of sleep apnea include right ventricular dysfunction with cor pulmonale, carbon dioxide retention during wakefulness as well as during sleep, and continuous reduced arterial oxygen tension. Hypersomnolent sleep apnea patients

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may be at risk for excessive mortality from these factors as well as from an elevated risk for accidents such as while driving or operating other potentially dangerous equipment. Although details of the pathogenesis of upper airway obstruction in sleep apnea patients have not been fully defined, it is generally accepted that the mechanism includes either anatomic or functional abnormalities of the upper airway which result in increased air flow resistance. Such abnormalities may include narrowing of the upper airway due to suction forces evolved during inspiration, the effect of gravity pulling the tongue back to appose the pharyngeal wall, and/or insufficient muscle tone in the upper airway dilator muscles. It has also been hypothesized that a mechanism responsible for the known association between obesity and sleep apnea is excessive soft tissue in the anterior and lateral neck which applies sufficient pressure on internal structures to narrow the airway. The treatment of sleep apnea has included such surgical interventions as uvalopalatopharyngoplasty, gastric surgery for obesity, and maxillo-facial reconstruction. Another mode of surgical intervention used in the treatment of sleep apnea is tracheostomy. These treatments constitute major undertakings with considerable risk of post-operative morbidity if not mortality. Pharmacologic therapy has in general been disappointing, especially in patients with more than mild sleep apnea. In addition, side effects from the pharmacologic agents that-have been used are frequent. Thus, medical practitioners continue to seek noninvasive modes of treatment for sleep apnea with high success rates and high patient compliance including, for example in cases relating to obesity, weight loss through a regimen of exercise and regulated diet. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Centralized hospital monitoring system for automatically detecting upper airway instability and for preventing and aborting adverse drug reactions Inventor(s): Lynn, Eric N.; (Villa Ridge, MO), Lynn, Lawrence A.; (Columbus, OH) Correspondence: Lawrence A. Lynn; 1507 CHAMBERS RD.; COLUMBUS; OH; 43212; US Patent Application Number: 20030000522 Date filed: May 17, 2002 Abstract: A system and method for the automatic diagnosis of obstructive sleep apnea in a centralized hospital critical care monitoring system for the monitoring of a plurality of patients in at least one of a critical care, step down, and cardiac ward by telemetry. The system includes a central processor having a display, and a plurality of telemetry units for mounting with patients, each of the telemetry units has a plurality of sensors for connection with each patient, the telemetry unit is capable of the transmission of multiple signals derived from the sensors to the central processor, in one preferred embodiment the method comprising steps of programming the system to analyze the signals and to automatically identify the presence and severity of obstructive sleep apnea and to provide an indication of the identification. Excerpt(s): This application claims priority of provisional application Nos. 60/291,691 and 60/291,687, both filed May 17, 2001 and provisional application No. 60/295,484 filed Jun. 10, 2001, the disclosures and contents of each of which is incorporated by reference as if completely disclosed herein. This invention relates to centralized hospital monitoring systems and particular to the organization, analysis, and automatic detection of patterns indicative of upper airway instability during sleep, deep sedation, and analgesia. This failure of conventional hospital based patient monitors to timely and/or

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automatically detect cluster patterns indicative of airway instability can be seen as a major health care deficiency indicative of a long unsatisfied need. Because obstructive sleep apnea, a condition derived from airway instability, is so common, the consequence of the failure of conventional hospital monitors to routinely recognize upper airway instability clusters means that many of patients with this disorder will never be diagnosed in their lifetime. For these patients, the diagnostic opportunity was missed and the health implications and risk of complications associated with undiagnosed airway instability and sleep apnea will persist in this group throughout the rest of their life. A second group of patients will have a complication in the hospital due to the failure to timely recognize airway instability. Without recognition of the inherent instability, a patient may be extubated too early after surgery or given too much narcotic (the right drug, the right patient, the ordered dose but unknowingly a "relative drug excess"). Indeed until clusters indicative of airway instability are routinely recognized by hospital monitors, the true incidence of respiratory failure, arrest, and/or death related to the administration of IV sedation and narcotics to patients in the hospital with airway instability will never be known but the number is probably in the tens of thousands each year and airway instability is just one example of the types of physiologic instability which are not automatically characterized by central hospital systems. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Combination treatment for sleep disorders including sleep apnea Inventor(s): Howard, Harry R. JR.; (Bristol, CT) Correspondence: PFIZER INC; 150 EAST 42ND STREET; 5TH FLOOR - STOP 49; NEW YORK; NY; 10017-5612; US Patent Application Number: 20020183306 Date filed: February 13, 2002 Abstract: The present invention relates to a method of treating sleep disorders including sleep apnea in a mammal, including a human, by administering to the mammal a 5HT1a antagonist or an alpha-2-adrenergic antagonist in combination with an SRI antidepressant agent with improvement in efficacy. It also relates to pharmaceutical compositions containing a pharmaceutically acceptable carrier, a 5HT1a antagonist or an alpha-2-adrenergic antagonist, and an SRI antidepressant agent. Excerpt(s): The present invention relates to a method of treating sleep disorders including sleep apnea with improved efficacy in a mammal, including a human, by administering to the mammal a 5HT1a antagonist or an alpha-2-adrenergic antagonist in combination with a serotonin reuptake inhibitor (SRI). It also relates to pharmaceutical compositions containing a pharmaceutically acceptable carrier, a serotonin 5HT1a antagonist or an alpha-2-adrenergic antagonist and a serotonin reuptake inhibitor (SRI). Sleep disorders including sleep apnea which are to be treated according to the present invention are of a psychiatric nature, and are to be diagnosed, and the treatment prescribed, by psychiatrists and other physicians. It will be understood that the patient and doctor cannot expect that such treatment will effect a cure in all cases. However, treatment according to the present invention, perhaps combined with other treatments such as psychiatric consultation and analysis, lifestyle modification, and perhaps other treatments for concomitant disorders, will be found to alleviate the disorder of sleep, producing a substantial benefit to the patient. In some cases, the benefit will be in the form of an alleviation of the unpleasant symptoms of the disorders, and in other cases

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substantial or even complete diminution of the symptoms will be obtained, amounting to complete cure of the disorder. Serotonin Selective Reuptake Inhibitors (SSRIs) currently provide efficacy in the treatment of major depressive disorder (MDD) and are generally perceived by psychiatrists and primary care physicians as effective, welltolerated and easily administered. However, they are associated with undesirable features, such as high incidence of sexual dysfunction, delayed onset of action and a level of non-responsiveness estimated to be as high as 30% (see M. J. Gitlin, Journal of Clinical Psychiatry, 1994, 55, 406-413 and R. T. Segraves, Journal of Clinical Psychiatry, 1992, 10(2), 4-10). Preclinical and clinical evidence has indicated that the sexual dysfunction associated with SSRI therapy can be reduced through the use of serotonin reuptake inhibitors (SRI) and dopamine reuptake inhibitors (DRIs), such as bupropion (see A. K. Ashton, Journal of Clinical Psychiatry, 1998, 59(3), 112-115). Furthermore, the combination of SRI and DRI may hasten the onset of action as well as offering relief to refractory patients, possibly through a synergistic mechanism (see R. D. Marshall et al, Journal of Psychopharmacology, 1995, 9(3), 284-286) and prove beneficial in the treatment of substance abuse and attention deficit hyperactivity disorder (ADHD) according to Barrickman et al, Journal of the American Academy of Child and Adolescent Psychology, 1995, 34(5), 649 and Shekim et al, Journal of Nervous and Mental Disease, 1989, 177(5), 296. Psychology, 1995, 34(5), 649 and Shekim et al, Journal of Nervous and Mental Disease, 1989, 177(5), 296. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Compositions comprising sibutramine phosphodiesterase inhibitors

metabolites

in

combination

with

Inventor(s): Fang, Qun K.; (Wellesley, MA), Jerussi, Thomas P.; (Framingham, MA), Senanayake, Chrisantha H.; (Shrewsbury, MA) Correspondence: PENNIE & EDMONDS LLP; 1667 K STREET NW; SUITE 1000; WASHINGTON; DC; 20006 Patent Application Number: 20030096792 Date filed: October 23, 2002 Abstract: Methods are disclosed for the treatment and prevention of disorders and conditions such as, but are not limited to: eating disorders; weight gain; obesity; irritable bowel syndrome; obsessive-compulsive disorders; platelet adhesion; apnea; affective disorders such as attention deficit disorders, depression, and anxiety; male and female sexual function disorders; restless leg syndrome; osteoarthritis; substance abuse including nicotine and cocaine addiction; narcolepsy; pain such as neuropathic pain, diabetic neuropathy, and chronic pain; migraines; cerebral function disorders; chronic disorders such as premenstrual syndrome; and incontinence.Pharmaceutical compositions and dosage forms are also disclosed which comprise a racemic or optically pure sibutramine metabolite and an optional additional pharmacologically active compound. Excerpt(s): This application is a continuation-in-part of U.S. patent application Ser. No. 09/662,135, filed Sep. 14, 2000, which is a continuation-in-part of U.S. patent application Ser. No. 09/372,158, filed Aug. 11, 1999, both of which are incorporated herein by reference in their entireties. The invention relates to methods of using and compositions comprising dopamine reuptake inhibitors such as racemic and optically pure metabolites of sibutramine, optionally in combination with other pharmacologically active compounds. Sibutramine, chemically named [N-1-[1-(4-chlorophenyl)cyclobutyl]-

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3- -methylbutyl]-N,N-dimethylamine, is a neuronal monoamine reuptake inhibitor which was originally disclosed in U.S. Pat. Nos. 4,746,680 and 4,806,570. Sibutramine inhibits the reuptake of norepinephrine and, to a lesser extent, serotonin and dopamine. See, e.g., Buckett et al., Prog. Neuro-psychopharm. & Biol. Psychiat., 12:575-584, 1988; King et al., J. Clin. Pharm., 26:607-611 (1989). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Detecting, assessing, and diagnosing sleep apnea Inventor(s): Beckman, Luke; (Arlington, VA), Beckman, Robert; (Arlington, VA), Crutchfield, Kevin E.; (Potomac, MD), Mozayeni, B. Robert; (Rockville, MD) Correspondence: HOGAN & HARTSON LLP; IP GROUP, COLUMBIA SQUARE; 555 THIRTEENTH STREET, N.W.; WASHINGTON; DC; 20004; US Patent Application Number: 20030176788 Date filed: January 28, 2003 Abstract: The present invention comprises methods for detecting, assessing, diagnosing, and pre-diagnosing sleep apnea, and for assessing the efficacy of a treatment for sleep apnea. Methods for the detection, assessment, diagnosis and pre-diagnosis (screening) of sleep apnea and the assessment of a treatment for sleep apnea according to the present invention may be performed in the absence of a sleep study. The patients subject to these methods may remain awake during their performance. The invention may be applied to other vascular conditions besides sleep apnea, wherein the sleep apnea methods described herein are example methods for the application of the present invention to the detection, assessment, diagnosis and pre-diagnosis (screening) of other vascular conditions. Excerpt(s): This application claims priority under 35 U.S.C.sctn. 119(e) to U.S. Provisional Patent Application No. 60/351,411, filed Jan. 28, 2002 and incorporated herein by reference. The invention relates to a system and method for assessing, diagnosing, and pre-diagnosing sleep apnea and assessing treatment of sleep apnea. Specifically, the invention relates to a system and method for identifying critical variables, through a Dynamic Vascular Assessment (DVA) of vascular Doppler data including transcranial Doppler (TCD) data, which distinguish patients suffering from sleep apnea and the normal population. Sleep apnea is a breathing disorder characterized by brief interruptions of breathing during sleep. Sleep apnea is usually caused by blockage in the lower portion of the throat, or by lack of impulse from the brain to control air passage in the respiratory system. Sleep apnea is often misdiagnosed as heart and lung problems. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Device and method for monitoring respiration Inventor(s): Page, Thomas C.; (Grasonville, MD) Correspondence: Levisohn, Lerner, Berger & Langsam; Suite 2500; 757 Third Avenue; New York; NY; 10017; US Patent Application Number: 20030199780 Date filed: April 22, 2002

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Abstract: A system and method are provided to monitor a patient's respiration during and after medical/surgical procedures, as well as in clinical situations wherein the patient is at increased risk for developing central or obstructive respiratory depression and/or apnea. A sensor attached to the patient's face, which monitors nasal and oral airflows. An electronic monitor analyzes patient respiratory patterns and initiates bedside and/or remote nursing station alarms in real time if and when a clinically significant respiratory event is detected. Respiration is measured by monitoring changes in the acoustic signature of the patient's breath passing over a corrugated or uneven surface, changes in the pressure of an inflatable closed volume of a sensor caused by the changes in temperature of the interior volume caused by the patient breathing over the sensor, or both. Excerpt(s): The present invention generally relates to respiratory sensor and alarm technology, and more particularly, relates to a dual mode respiratory airflow sensor and monitoring technology for the detection of any and all potentially life threatening respiratory events. It is known in the art to monitor patients susceptible to disorders of the respiratory system, or in critical care settings, to employ respiration sensors and alarm systems. U.S. Pat. No. 4,878,502 issued to Dietz discusses a respiration airflow sensor employing a tube in which a ball is free to move, thereby breaking a beam of light. The ball is forced to move by the flow of air associated with the breathing of the patient. In U.S. Pat. No. 4,745,925 also issued to Dietz, another variation of an opthoelectric inhalation sensor using thin film deposition is discussed. Monitoring of respiration disorders by acoustic sensors is mentioned in U.S. Pat. No. 4,602,644 issued to DeBenedetto et al., and in U.S. Pat. No. 4,595,016 issued to Fertig et al. U.S. Pat. No. 4,366,821 issued to Wittmaier et al. shows a respiration monitoring system, which preferably uses a gas sensor. U.S. Pat. No. 4,350,166 issued to Mobarry shows an infant respiration detector of long wave infrared light which is absorbed by carbon dioxide. When an infant's exhalation (and thus its production of carbon dioxide) is interrupted, an alarm is activated. In U.S. Pat. No. 4,326,404 issued to Mehta, moisture is sensed using a sodium chloride crystal. U.S. Pat. No. 4,306,867 issued to Krasner shows the use of a pressure sensor. An impedance plethysmograph is employed in U.S. Pat. No. 4,289,142 issued to Kearns. The use of thermoresistive sensors is suggested in U.S. Pat. No. 3,903,876 issued to Harris, U.S. Pat. No. 3,884,219 issued to Richardson et al., and U.S. Pat. No. 3,999,537 issued to Noiles. All of the above methods are complicated and expensive, or else unworkable in a real hospital setting for perioperative patients. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Device for preventing sleep apnea Inventor(s): Masayoshi, Furuya; (Nagano-shi, JP), Narihiko, Matsuda; (Kobe-shi, JP) Correspondence: BIRCH STEWART KOLASCH & BIRCH; PO BOX 747; FALLS CHURCH; VA; 22040-0747; US Patent Application Number: 20030056785 Date filed: September 26, 2002 Abstract: The present invention provides a device which prevents loud snoring and apnea during sleep so as not to cause discomfort to a user as much as possible. Stoppers 4 such as belts or straps having predetermined elasticity are attached to both right and left sides of a lower jaw fitting piece 3 which fits the both sides of the lower jaw, the lower jaw 2 is pushed forward via the lower jaw fitting piece 3 by setting and hanging

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the stoppers 4 on the nose or head of the face side, whereby occurrence of apnea and loud snoring during sleep is prevented. Excerpt(s): The present invention relates to a device for preventing sleep apnea in the field of oral medical treatment. There are surprisingly many people who snore during sleep, and some of them suffer from sleep apnea. Snoring is caused by muscle relaxation during sleep, and when the jaw muscle relaxes, the lower jaw moves rearward and moves the tongue to the rear side of the oral cavity, whereby the breathing airway of the pharynx is narrowed, the breathing airflow eddies, the velum and the surrounding soft muscle vibrates and causes a sound phenomenon called snoring. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Fiber optic interferometric vital sign monitor for use in magnetic resonance imaging, confined care facilities and in-hospital Inventor(s): Jeffers, Larry A.; (Minerva, OH), Maida, John L. JR.; (Houston, TX), Varshneya, Deepak; (Del Mar, CA) Correspondence: WATTS, HOFFMANN, FISHER & HEINKE CO., L.P.A.; P.O. Box 99839; Cleveland; OH; 44199-0839; US Patent Application Number: 20030095263 Date filed: November 19, 2002 Abstract: A fiber optic monitor that utilizes optical phase interferometry to monitor a patient's vital signs such as respiration, cardiac activity, blood pressure and body's physical movement. The monitor, which is non-invasive, comprises an optical fiber interferometer that includes an optical fiber proximately situated to the patient so that time varying acousto-mechanical signals from the patient are coupled into the optical fiber. Responsive thereto, the interferometer generates a time-varying optical intensity resulting from the interference of optical signals, which are detected at a photo-detector. A signal processor coupled to the optical detector provides one or more processed output signals indicative of the vital functions. The monitor system has broad applicability, from routine monitoring of infants at home to detection of apnea, arrhythmia, blood pressure and trauma. The system can be implemented in embodiments ranging from a low cost in-home monitor for infants to a high end product for in hospital use. The monitor can be integrated with other sensors such as an EKG, a video or still camera, an oxygen sensor, a carbon dioxide sensor, temperature sensor or a microphone to get additional required information depending on the application. When integrated and combined with EKG information, the monitor provides ballisto-mechanical information of the heart for early diagnosis of cardiac conditions or prediction of events or for correcting corrupted EKG signals due to time varying magnetic and electric fields. In some embodiments of the monitor, the system can be made portable so that the patient can walk around while still being continuously monitored for vital signs. Another suitable design measures blood pressure continuously and non-invasively by containing the fiber optic sensor in a cuff that wraps around an arterial wall of the patient. The fiber optic monitor may be designed for use in a variety of settings including an operating room, a recovery room, an intensive care unit, a magnetic resonance imaging laboratory, a computerized tomography scan laboratory and an elderly care facility. Excerpt(s): This is a continuation-in-part of patent application Ser. No. 09/499,889 entitled, "Fiber Optic Monitor Using Interferometry for Detecting Vital Signs of a

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Patient," filed on Feb. 8, 2000, which is incorporated herein by reference in its entirety. The present invention generally relates to vital sign monitors for detecting physiological parameters such as heartbeat, respiration, physical movement, blood pressure and other bodily activities of a patient for use in a magnetic resonance imaging (MRI) environment, confined care facilities (e.g., geriatrics) and in-hospital during surgery, postoperative recovery and intensive care units. 5. The RF coils in the MRI pick up these spatially encoded RF signals emitted from the tissues and are transformed by a computer into 2 or 3 dimensional images. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Flow diverter for controlling the pressure and flow rate in a CPAP device Inventor(s): Bullock, Denis L.; (Milton, AU), McAuliffe, Patrick J.; (Carlingford, AU) Correspondence: PILLSBURY WINTHROP, LLP; P.O. BOX 10500; MCLEAN; VA; 22102; US Patent Application Number: 20030127096 Date filed: January 8, 2002 Abstract: A flow diverter valve is used in controlling the pressure and/or flow rate of a breathable gas supplied to the airways of a patient by a breathable gas flow generator supply apparatus during, for example, ventilatory assistance treatments such as noninvasive positive pressure ventilation and nasal Continuous Positive Airway Pressure (CPAP) treatment of Obstructive Sleep Apnea. The flow diverter valve includes a vane and a housing. The housing has an inlet port, an outlet port, and an exhaust port. The exhaust port opens to atmosphere, and the inlet port is in fluid communication with the flow generator. The outlet port is in fluid communication with a patient mask via a conduit. The vane is configured with respect to the housing such that a blower associated with the CPAP apparatus remains substantially unchoked, regardless of whether the vane is in the open or closed position. Excerpt(s): This application is related to pending U.S. patent application Ser. No. 09/598,053 filed on Jun. 21, 2001, describing a control member for a valve and method for determining fluid flow rate through a valve. This application is also related to U.S. patent application Ser. No. 09/642,824 filed on Aug. 22, 2000, describing pressure control in CPAP treatment or assisted respiration. International PCT Patent Application No. PCT/AU97/00631 describes varying pressure at a patient mask through the period of treatment during inspiration or expiration, and International PCT patent application No. PCT/AU96/00586 describes a flow diverting valve with a rotatable control member, both of which are related to this application. The contents of these U.S. and International PCT Patent Applications are incorporated herein by reference in their entireties. This application is also related to U.S. Pat. No. 4,944,310, which describes Continuous Positive Airway Pressure (CPAP) treatment, and U.S. Pat. No. 5,245,995 which describes automatically adjusting nasal CPAP treatment. The contents of these patents are incorporated herein by reference in their entireties. The present invention relates to a ventilatory assistance apparatus, and in particular, a ventilatory assistance apparatus including a flow diverter valve in fluid communication with a flow generator. NonInvasive Positive Pressure Ventilation (NIPPV) is a form of treatment for breathing disorders which can involve a relatively higher pressure of air or other breathable gas being provided to the entrance of a patient's airways via a patient mask during the inspiratory phase of respiration, and a relatively lower pressure or atmospheric pressure being provided in the patient mask during the expiratory phase of respiration. In other

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NIPPV modes the pressure can be made to vary in a complex manner throughout the respiratory cycle. For example, the pressure at the mask during inspiration or expiration can be varied through the period of treatment. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

INDOLINE DERIVATIVES AND METHOD OF TREATING OBESITY Inventor(s): Bentley, Jonathan Mark; (Winnersh, GB), Davidson, James Edward Paul; (Winnersh, GB), Mansell, Howard Langham; (Winnersh, GB), Monck, Nathaniel Julius Thomas; (Winnersh, GB) Correspondence: HOFFMANN-LA ROCHE INC.; PATENT LAW DEPARTMENT; 340 KINGSLAND STREET; NUTLEY; NJ; 07110 Patent Application Number: 20020183349 Date filed: October 15, 2001 Abstract: The present invention relates to indoline derivatives. These compounds are especially useful for the prevention and treatment of disorders of the central nervous system; damage to the central nervous system; cardiovascular disorders; gastrointestinal disorders; diabetes, sleep apnea, and especially for the treatment and prevention of obesity. Excerpt(s): The present invention relates to indoline derivatives, to processes and intermediates for their preparation, to pharmaceutical compositions comprising them and to their medicinal use. The active compounds of the present invention are useful in treating obesity, diabetes and other disorders. It has been recognised that obesity is a disease process influenced by environmental factors in which the traditional weight loss methods of dieting and exercise need to be supplemented by therapeutic products (S. Parker, "Obesity: Trends and Treatments", Scrip Reports, PJB Publications Ltd, 1996). Whether someone is classified as overweight or obese is generally determined on the basis of their body mass index (BMI) which is calculated by dividing body weight (kg) by height squared (m.sup.2). Thus, the units of BMI are kg/m.sup.2 and it is possible to calculate the BMI range associated with minimum mortality in each decade of life. Overweight is defined as a BMI in the range 25-30 kg/m.sup.2, and obesity as a BMI greater than 30 kg/m.sup.2. There are problems with this definition in that it does not take into account the proportion of body mass that is muscle in relation to fat (adipose tissue). To account for this, obesity can also be defined on the basis of body fat content: greater than 25% and 30% in males and females, respectively. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Infant cardiac and apnea home monitoring system Inventor(s): Holland, Teresa C.; (Greenfield, IN), Suskovich, Mick C.; (Indianapolis, IN) Correspondence: Robert A. Spray; Patent Attorney; 5215 Fawn Hill Terrace; Indianapolis; IN; 46226; US Patent Application Number: 20030055350 Date filed: September 14, 2001 Abstract: An infant cardiac and apnea home monitoring system, which provides audible, visual, and other auxiliary sensory alarms and also includes the ability to

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transmit an encrypted signal to an Emergency Message Retrieval Unit (EMRU), which in itself contains audible, visual, and touch sensory alarms.The ability of the Personal Home Baby Monitor (PHBM) to identify when an infant's heart or respiratory rate is not within the pre-set parameters will result in the activation of an alarm state Once the PHBM has entered an alarm state, the base unit will trigger all available alerts, including the simultaneous transmission of a low frequency enable and a high frequency modulated signal, from the base unit to the EMRU. The EMRU upon successfully decoding and validation of the signal will trigger its sensory alarms. Excerpt(s): The conceptual idea for the design was initially brought about by the acknowledgement that: parents affected by physical ailments were more challenged to care for newborn children, due to the lack of sufficient monitoring systems. Existing monitoring technologies fail to satisfy the needs of wanting parents. The focus of the design became based on providing a solution for the dilemma at hand. The overall purpose of the invention is to assure parents who are sensory challenged to be notified of a life-threatening event that requires an emergency response. A robust and dynamic system for monitoring young children that allows parents to be notified of a life threatening event that requires an emergency response. The invention encapsulates special considerations for parents who have sensory disabilities. The invention is comprised of three sub systems: A sensory system that utilizes open end electrodes that are physically attached to a young child; A portable base that is connected to the sensory system and monitors the electrical impulses transmitted by the electrodes, manages alarm states, encapsulates and triggers alarms, and also transmits simultaneous high and low frequency signals during alarm states; and an EMRU that receives signals, decodes signals, and triggers alarm states. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Medicament for combating respiratory depression Inventor(s): Chizh, Boris; (Cambridge, GB), Christoph, Thomas; (Aachen, DE), Zimmer, Oswald; (Wuerselen, DE) Correspondence: PERMAN & GREEN; 425 POST ROAD; FAIRFIELD; CT; 06824; US Patent Application Number: 20030130203 Date filed: November 21, 2002 Abstract: The invention relates to the use of at least one compound of general formula (I) and/or one of its diastereomers and/or one of its enantiomers and/or one of the corresponding physiologically compatible salts for producing a medicament for combating respiratory depression, with the exception of medicaments for combating respiratory depression as a cause of sleep apnea. Excerpt(s): The present invention relates to the use of at least one compound of general formula I and/or one of its diastereoisomers and/or one of its enantiomers and/or one of the corresponding physiologically acceptable salts for the preparation of a medicament for combating respiratory depression, with the exception of medicaments for combating respiratory depression as a cause of sleep apnoea. The occurrence of respiratory depression, e.g. when administering compounds with opioid activity, in states of shock, when administering psychotropic drugs or in cases of central respiratory regulation disorders, is a situation which arises relatively frequently in clinical practice and is not uncommonly life-threatening for the patient. There is therefore a worldwide need for effective therapies for combating respiratory depression, as documented in the

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large number of scientific papers which have recently appeared in this field from the sectors of both clinical practice and fundamental research. The object of the invention was therefore to provide medicaments suitable for combating respiratory depression, especially for combating respiratory depression when administering compounds with opioid activity, in states of shock, when administering psychotropic drugs or in cases of central respiratory regulation disorders. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method and apparatus for optimizing the continuous positive airway pressure for treating obstructive sleep apnea Inventor(s): Gruenke, Roger A.; (Overland Park, KS), Norman, Robert G.; (New Windsor, NY), Rapoport, David M.; (New York, NY) Correspondence: FULWIDER PATTON LEE & UTECHT, LLP; HOWARD HUGHES CENTER; 6060 CENTER DRIVE; TENTH FLOOR; LOS ANGELES; CA; 90045; US Patent Application Number: 20030055346 Date filed: November 7, 2002 Abstract: A diagnostic device having a nose fitting used without connection to a breathing gas supply for obtaining flow data values at ambient pressure. The nose fitting is connected to a pressure or flow sensor that supplies data values to a microprocessor. The detection and measurement of breathing gas flow is made from a tight sealing nose fitting (mask or prongs) configured with a resistive element inserted in the flow stream as breathing gas exits from and enters into the fitting. The nasal fitting is further provided with a port for connection to a flow or pressure transducer. The resistive element causes a pressure difference to occur between the upstream side and the downstream side when air flows through the element. The data values may be stored in computer memory to be analyzed for flow limitations. Excerpt(s): This application is a continuation of U.S. Ser. No. 09/602,158, filed Jun. 22, 2000, which is a continuation of U.S. application Ser. No. 08/644,371, filed May 10, 1996 (U.S. Pat. No. 6,299,581), which is a continuation of U.S. application Ser. No. 08/482,866, filed Jun. 7, 1995 (U.S. Pat. No. 5,535,739), which is a division of U.S. application Ser. No. 08/246,964, filed May 20, 1994 (U.S. Pat. No. 5,490,502), which is a continuation-in-part of U.S. application Ser. No. 07/879,578, filed May 7, 1992 (U.S. Pat. No. 5,335,654), the contents of which are hereby incorporated herein by reference. This invention relates to a method and apparatus for adjusting the positive airway pressure of a patient to an optimum value in the treatment of obstructive sleep apnea, and more particularly to a breathing device which maintains constant positive airway pressure and method of use which analyzes an inspiratory flow waveform to titrate such a pressure value. Obstructive sleep apnea syndrome (OSAS) is a well recognized disorder which may affect as much as 1-5% of the adult population. OSAS is one of the most common causes of excessive daytime somnolence. OSAS is most frequent in obese males, and it is the single most frequent reason for referral to sleep disorder clinics. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Method and apparatus for providing positive airway pressure to a patient Inventor(s): Estes, Mark C.; (Sylmar, CA), Fiore, John; (Monroeville, PA), Kepler, Jeff; (Pittsburgh, PA), Mechlenburg, Douglas M.; (Murrysville, PA), Ressler, Heather; (New Alexandria, PA) Correspondence: MICHAEL W. HAAS, INTELLECTUAL PROPERTY COUNSEL; RESPIRONICS, INC.; 1010 MURRY RIDGE LANE; MURRYSVILLE; PA; 15668; US Patent Application Number: 20030121519 Date filed: November 26, 2002 Abstract: A system including methods and apparatus for treatment of a medical disorder such as obstructive sleep apnea or congestive heart failure. The system involves applying a gain to flow rate of pressurized gas delivered to a patient during inspiratory and/or expiratory phases of a respiratory cycle to deliver the pressurized gas in proportion to the respective gains during inspiration and/or expiration. A base pressure may be applied in addition to the gain-modified pressures and an elevated pressure profile may be employed to assist or control inspiration. The system may be fully automated responsive to feedback provided by a flow sensor that determines the estimated patient flow rate. A leak computer can be included to instantaneously calculate gas leakage from the system. The system may be utilized in connection with conventional continuous positive airway pressure treatments, such as CPAP or bi-level positive airway pressure equipment to effect various beneficial treatment applications. Excerpt(s): This is a continuation-in-part of U.S. patent application Ser. No. 09/610,733 filed Jul. 6, 2000, which is a continuation of U.S. patent application Ser. No. 09/041,195 filed Mar. 12, 1998, now U.S. Pat. No. 6,105,575, which is a continuation-in-part of U.S. patent application Ser. No. 08/679,898 filed Jul. 15, 1996, which is a continuation-in-part of application Ser. No. 08/253,496 filed Jun. 3, 1994, now U.S. Pat. No. 5,535,738. The present invention relates generally to methods and apparatus for treating breathing and/or cardiac disorders and, more particularly, to methods and apparatus for providing a pressure to an airway of a patient during at least a portion of the breathing cycle to treat obstructive sleep apnea syndrome, chronic obstructive pulmonary disease, congestive heart failure, and other respiratory and/or breathing disorders. During obstructive sleep apnea syndrome (OSAS), the airway is prone to narrowing and/or collapse while the patient sleeps. Continuous positive airway pressure (CPAP) therapy seeks to avoid this narrowing by supplying pressure to splint the airway open. With CPAP, this splinting pressure is constant and is optimized during a sleep study to be sufficient in magnitude to prevent narrowing of the airway. Providing a constant splinting pressure, i.e., CPAP, is a simple solution to the problem posed by the collapsing airway. However, this approach exposes the patient to pressures that are higher than the pressures needed to support the airway for most of the breathing cycle. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Method and apparatus for the treatment of central sleep apnea using biventricular pacing Inventor(s): Burnes, John E.; (Andover, MN), Cho, Yong K.; (Maple Grove, MN) Correspondence: MEDTRONIC, INC.; 710 MEDTRONIC PARKWAY NE; MS-LC340; MINNEAPOLIS; MN; 55432-5604; US Patent Application Number: 20030195571 Date filed: April 12, 2002 Abstract: An apparatus and method for treating sleep apnea includes a control unit in electrical communication with a lead. The control unit is capable of outputting a sleep apnea interruption pulse to stimulate at least one of a phrenic nerve and a diaphragm. Specifically, an implanted medical device (IMD) such as an ICD or a pacemaker paces the heart and a mode switch algorithm changes the pacing output to stimulate at least one of a phrenic nerve and diaphragm when sleep apnea is detected by the control unit. The method includes determining if the patient is experiencing sleep apnea and outputting a sleep apnea interruption pulse to the at least one of a phrenic nerve and a diaphragm. The control unit may be incorporated with the IMD. In another embodiment, the control unit may be in wireless communication with the IMD and positioned outside a patient's body. Excerpt(s): The present invention generally relates to implantable medical devices. Specifically, the invention relates to the prevention of hypopnia during sleep apnea by stimulating the phrenic nerve with implanted cardiac leads, when the onset of sleep apnea is detected. More specifically, the invention relates to a biventricular pacemaker adapted to provide an automatically adjustable output via a lead preferably located in the coronary sinus. Sleep apnea is generally associated with the cessation of breathing during sleep. The medical characteristics of sleep apnea have been known for some time. Sleep apnea is terminated by the subject's arousal, followed by hyperventilation. Such arousals from sleep are generally associated with increased sympathetic nervous system activity and blood pressure, which may contribute to the worsening of a patient's cardiac condition. Generally, there are two types of sleep apnea. The first is central sleep apnea, which relates to the failure of the body to automatically generate the neuro-muscular stimulation necessary to initiate and control the respiratory cycle at the proper time. The second sleep apnea syndrome is known as obstructive sleep apnea. This generally relates to an obstructive apnea that includes reduction of the size of the superior airways, an increase in their compliance and reduction in the activity of the dilator muscles. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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METHOD AND APPARATUS FOR TREATMENT OF SNORING, HYPOPNEA AND APNEA Inventor(s): Kulick, George; (Freeland, PA) Correspondence: GEORGE KULICK; 1220 W. PLEASANT VALLEY ROAD; PARMA; OH; 44134; US Patent Application Number: 20020139375 Date filed: April 2, 2001

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Abstract: A one-piece oral device for treatment of obstructive sleep disorders such as snoring, hypopnea and apnea comprising a mouthpiece portion that fits within the anterior part of the oral cavity of a person much like the mouthpieces used in snorkel and scuba devices when swimming. The anterior or forward part of the mouthpiece protrudes outwardly through the lips of the user and includes a tongue shaped cavity for receiving the tongue. Bite blocks extending interiorly of the mouthpiece maintain the teeth in spaced-apart relation preventing damage to the tongue. A small channel communicates with the tongue shaped cavity and is connected via a length of tubing to an outside source of low suction pressure for holding the tongue forward. Excerpt(s): The disruption of sleep causes excessive sleepiness during the working hours. Sleep research in the past few years suggest that snoring even without sleep apnea syndrome may also disturb sleep significantly. Sleepiness is a global epidemic. Fatigue accounts for about 40 percent of commercial trucking accidents, which causes 4,000 deaths and 12,000 injuries per year. It also causes a breakdown in marital and family ties. The true nature of the challenge, i.e., to identify and treat the millions of people who have sleep apnea syndrome, is truly staggering. Patients with sleep apnea syndrome are in danger of harming themselves and may be at risk to others. The present invention has been developed to aid in the elimination of snoring and the various degrees of hypopnea and apnea that occur due to pathological disturbances in the sleep process. One of the main reasons of the sleep disturbance is the relaxation of the tongue to varying degrees during the several stages of sleep. When fully awake, the tongue has normal tone as air normally passes in and out of the lungs during respiration. However, during sleep, the tongue is lax. As air is drawn into the lungs by the muscles of respiration, the tongue is drawn back against the posterior wall of the pharynx in a fluttering fashion. As the posterior part of the tongue hits the posterior wall of the pharynx with rapidity, the to and fro action of the tongue causes loud and disturbing snoring sounds. When sleeping a supine position, the effect of gravity makes the snoring worse. The more serious type of sleep disturbance is obstructive sleep apnea, which occurs when the tongue goes against the posterior wall of the pharynx preventing any air from entering the lungs. The effort of the muscles of respiration causes the blockage to seal even tighter. The apnea causes a drop in the blood oxygenation and increases the blood carbon dioxide level. The heart is affected adversely with the blood pressure and pulse rate increasing. Sometimes arrhythmias may occur. The brain is affected by the carbon dioxide buildup causing the person to be aroused. On awakening there is a return to tonicity of the muscles of the tongue, which allow normal breathing to resume. After some time the person goes back to sleep and the process occurs all over again. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method and apparatus to detect and monitor the frequency of obstructive sleep apnea Inventor(s): Cho, Yong K.; (Maple Grove, MN), Condie, Catherine R.; (Shoreview, MN), Jensen, Donald N.; (Derwood, MD) Correspondence: MEDTRONIC, INC.; 710 MEDTRONIC PARKWAY NE; MS-LC340; MINNEAPOLIS; MN; 55432-5604; US Patent Application Number: 20030204213 Date filed: April 30, 2002 Abstract: The present invention provides a method and apparatus for detecting and monitoring obstructive sleep apnea. The apparatus includes an intracardiac impedance

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sensor to measure intracardiac impedance, a movement sensor to measure an amount of movement of a patient, and a controller operatively coupled to said intracardiac impedance sensor and said movement sensor, said controller adapted to receive at least one of an intracardiac impedance and the amount of movement of the patient and detect obstructive sleep apnea based upon said intracardiac impedance and said movement. Excerpt(s): This invention relates generally to implantable medical devices, and more particularly, to a method and apparatus to automatically detect and monitor the frequency of obstructive sleep apnea. Although the function of sleep is not well understood, one consequence of an inadequate quantity or poor quality of sleep is an inability to maintain adequate wakefulness. The amount of sleep an individual needs is thought to be neurologically determined and is generally stable over time. Among other factors, an insufficient amount of sleep (i.e., quantity of sleep) or a disruption of sleep continuity (i.e., quality of sleep) will result in increased daytime sleepiness. Increased sleepiness in a person may cause a plethora of problems to that person as well as others. Increased sleepiness is a major cause of accidents because people who are sleepy are generally not fully aware of their surroundings. Additionally, because of this decreased awareness, a person who does not receive the adequate quantity and quality of sleep at night may also be prone to decreased efficiency at home and at work. A sleepy person may also require frequent naps during the day to recuperate, thereby reducing productivity in the office as well as in the chores of daily life. As a result, it is important for people generally to receive a good night's rest. However, many people have medical conditions that prevent them from receiving a good night's rest. One such condition is sleep apnea. Sleep apnea is generally defined as the cessation of breathing during sleep. One type of a sleep apnea, obstructive sleep apnea ("OSA"), is caused by repetitive upper airway obstruction during sleep as a result of narrowing of the respiratory passages. Partial obstruction of the passageways may simply lead to hypopnea. Prolonged obstruction of the passageways, however, may lead to nocturnal arousals. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method and apparatus to treat conditions of the naso-pharyngeal area Inventor(s): Conrad, Timothy R.; (Eden Prairie, MN), Knudson, Mark B.; (Shoreview, MN), Tweden, Katherine S.; (Mahtomedi, MN) Correspondence: MERCHANT & GOULD PC; P.O. BOX 2903; MINNEAPOLIS; MN; 55402-0903; US Patent Application Number: 20020170564 Date filed: July 3, 2002 Abstract: A patient's upper airway condition such as snoring and sleep apnea is treated by selecting a particulate material selected for limited migration within tissue and for encouraging a fibrotic response of tissue to the material. A bolus of the particulate material is injected into the tissue area to structurally stiffen the tissue. Excerpt(s): This invention is directed to methods and apparatuses for treating conditions of the naso-pharyngeal area such as snoring and sleep apnea. More particularly, this invention pertains to method and apparatus to stiffen tissue of the naso-pharyngeal area. Snoring has received increased scientific and academic attention. One publication estimates that up to 20% of the adult population snores habitually. Huang, et al., "Biomechanics of Snoring", Endeavour, p. 96-100, Vol. 19, No. 3 (1995). Snoring can be a serious cause of marital discord. In addition, snoring can present a serious health risk to

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the snorer. In 10% of habitual snorers, collapse of the airway during sleep can lead to obstructive sleep apnea syndrome. Id. Notwithstanding numerous efforts to address snoring, effective treatment of snoring has been elusive. Such treatment may include mouth guards or other appliances worn by the snorer during sleep. However, patients find such appliances uncomfortable and frequently discontinue use (presumably adding to marital stress). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method and device for addressing sleep apnea and related breathing disorders Inventor(s): Britt, Walter; (Wayland, MI), Heeke, David W.; (East Lansing, MI) Correspondence: Denise M. Glassmeyer; Dierker & Glassmeyer, P.C.; 3331 W. Big Beaver, Suite 109; Troy; MI; 48084; US Patent Application Number: 20030015198 Date filed: June 14, 2002 Abstract: A device which is removably insertable in the mouth for facilitating breathing while sleeping which provides a clear unobstructed airway by protrusive positioning of the mandible and/or delivery of pressurized air to the back of the mouth. The device has upper and lower tooth-contacting members and an airway defined between them. Excerpt(s): This application claims the benefit of U.S. Provisional Applications S. No. 60/298,997, filed Jun. 18, 2001. The invention relates to oral appliances and methods for making same. More particularly the present invention relates to oral appliances which can facilitate breathing while sleeping. Difficulty breathing while sleeping often manifests itself as snoring or, the more serious condition, obstructive sleep apnea. Snoring is a condition affecting approximately 40% of the adult population, while obstructive sleep apnea affects approximately 7% of the adult population. Although snoring can occur as a result of a physical anomaly, such as enlarged tonsils or adenoids, generally, snoring occurs during sleep because the muscles of the upper throat relax. As a person breathes, the turbulence of the air causes a flutter valve effect on the soft tissues of the upper throat. The vibration resulting from the flutter valve effect of the soft tissues of the upper throat causes snoring sounds. Airway occlusion during sleep may cause cessation of breathing (apnea) and can lead to undesirable physiological symptoms. Sleep apnea is due to the obstruction of the upper airway which produces short episodes of breathing stoppage that characterizes apnea. Frequent arousals during the night occur when the user awakens in order to overcome the airway blockage. As a result, sleep apnea can contribute to excessive daytime sleepiness as well as high blood pressure, strokes or cardiac arrest. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Methods and apparatus for stroke patient treatment Inventor(s): Ujhazy, Anthony John; (East Lindfield, AU), Wright, Jonathan Caldwell; (Balgowlah, AU) Correspondence: Gottlieb, Rackman & Reisman, P.C.; 270 Madison Avenue; New York; NY; 10016-0601; US Patent Application Number: 20020185130 Date filed: December 11, 2001 Abstract: Methods and apparatus for assessing the condition of and treating patients for stroke during the delivery of continuous positive airway pressure (CPAP) are disclosed. By determining central and obstructive apnea occurrences or the percentile of pressure delivered to the patient from patient airflow, stroke indicators may be calculated and analyzed to provide information on the type of stroke a patient has suffered and the degree of a patient's neuro-recovery. The apparatus may be programmed with a particular protocol intended to identify between alternative forms of CPAP treatment appropriate for the patient based upon an assessment of the patient's condition. The device can select and recommend between the various treatment forms, identify billing reimbursement codes and generate data to track patient response to stroke treatments. Excerpt(s): This application claims the priority filing date of U.S. provisional patent application serial No. 60/254,151 filed on Dec. 11, 2000. The invention relates to methods and apparatus for diagnosing, managing and treating stroke patients both as in-patients and out-patients. Stroke, or brain attack as it is commonly called, can be caused by either vascular hemorrhage or vascular blockage with the latter accounting for about 80% of the events which lead to a stroke. Vascular hemorrhage is also termed a haemorrhagic stroke or an aneurism. Vascular blockage may also be termed ischaemic stroke. Both types of stroke are associated with considerable morbidity in terms of longterm neurological deficit and the risk of subsequent stroke as well as mortality post stroke. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Methods for treating apnea and apnea disorders using optically pure (+) norcisapride Inventor(s): Barberich, Timothy J.; (Concord, MA), Rubin, Paul D.; (Sudbury, MA) Correspondence: PENNIE & EDMONDS LLP; 1667 K STREET NW; SUITE 1000; WASHINGTON; DC; 20006 Patent Application Number: 20020147220 Date filed: February 15, 2002 Abstract: Methods for the prevention, treatment, or management of apnea, apnea disorders, bulimia nervosa, irritable bowel syndrome, urinary incontinence, bradycardia, bradyarrhythmia, syncope, other disorders, or symptoms thereof using (+) norcisapride, or a pharmaceutically acceptable salt thereof, substantially free of its (-) stereoisomer. Excerpt(s): The invention relates to methods of prevention, treatment, or management, of apnea, apnea disorders, bulimia, other disorders, or symptoms thereof. Apnea is defined in Stedman's Medical Dictionary, 26.sup.th Edition, Williams and Wilkins (1995), as the absence of breathing. There are a number of disorders associated with apnea, which are characterized by interrupted breathing in which a person stops

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breathing long enough to decrease the amount of oxygen and increase the amount of carbon dioxide in the blood and brain. Each type of apnea involves the absence of airflow at the nose or the mouth, typically for at least 10 seconds. Various apnea disorders exist, including: central apnea, which results from medullary depression and inhibits respiratory movement; deglutition apnea, which is the inhibition of breathing during swallowing; obstructive or peripheral apnea, which is either a result of obstruction of air passages or inadequate respiratory muscle activity; sleep apnea, which is central and/or obstructive apnea during sleep; and sleep induced apnea, which results from failure of the respiratory center to stimulate adequate respiration during sleep. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Methods for treating dementia due to HIV disease Inventor(s): Pratt, Raymond; (Leonia, NJ) Correspondence: Edward D. Grieff, Esq.; Hale and Dorr LLP; 1455 Pennsylvania Avenue, NW; Washington; DC; 20004; US Patent Application Number: 20030040532 Date filed: September 3, 2002 Excerpt(s): This application is a continuation of U.S. application Ser. No. 09/947,086 filed Sep. 4, 2001, which is a continuation of PCT Application No. PCT/US01/07027 filed Mar. 5, 2001, which claims priority to U.S. Provisional Application No. 60/259,226 filed Jan. 3, 2001, U.S. Provisional Application No. 60/220,783 filed Jul. 25, 2000, U.S. Provisional Application No. 60/197,610 filed Apr. 18, 2000, and U.S. Provisional Application No. 60/186,744 filed Mar. 3, 2000. The invention describes novel methods for treating and preventing dementia caused by vascular diseases; dementia associated with Parkinson's disease; Lewy Body dementia; AIDS dementia; mild cognitive impairments; age-associated memory impairments; cognitive impairments and/or dementia associated with neurologic and/or psychiatric conditions, including epilepsy, brain tumors, brain lesions, multiple sclerosis, Down's syndrome, Rett's syndrome, progressive supranuclear palsy, frontal lobe syndrome, and schizophrenia and related psychiatric disorders; cognitive impairments caused by traumatic brain injury, post coronary artery by-pass graft surgery, electroconvulsive shock therapy, and chemotherapy, by administering a therapeutically effective amount of at least one of the cholinesterase inhibitor compounds described herein. The invention also describes novel methods for treating and preventing delirium, Tourette's syndrome, myasthenia gravis, attention deficit hyperactivity disorder, autism, dyslexia, mania, depression, apathy, and myopathy associated with or caused by diabetes by administering a therapeutically effective amount of at least one of the cholinesterase inhibitor compounds described herein. The invention also describes novel methods for delaying the onset of Alzheimer's disease, for enhancing cognitive functions, for treating and preventing sleep apnea, for alleviating tobacco withdrawal syndrome, and for treating the dysfunctions of Huntington's Disease by administering a therapeutically effective amount of at least one of the cholinesterase inhibitor compounds described herein. A preferred cholinesterase inhibitor for use in the methods of the invention is donepezil hydrochloride or ARICEPT.RTM. Novel cholinesterase inhibitors are described in U.S. Pat. No. 4,895,841 and WO 98/39000, the disclosures of which are incorporated by reference herein in their entirety. The cholinesterase inhibitors described in U.S. Pat. No.

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4,895,841 include donepezil hydrochloride or ARICEPT.RTM., which has proven to be a highly successful drug for the treatment of Alzheimer's disease. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Microcompetition and human disease Inventor(s): Polansky, Hanan; (Rochester, NY) Correspondence: Brown, Pinnisi and Michaels, P.C.; 400 M&T Bank Building-118 North Tioga Street; Ithaca; NY; 14850-4343; US Patent Application Number: 20030092601 Date filed: December 7, 2000 Abstract: Cellular microcompetition for the transcription factor human GA binding protein (GABP) is a risk factor associated with obesity and obesity-related diseases such as osteoarthritis, atherosclerosis, obstructive sleep apnea, various cancers, and periodontitis. The invention uses this novel discovery to develop assays which determine the level of microcompetition in a cell. Other assays developed from the knowledge that microcompetition is occurring in cells are also disclosed. This novel discovery led to the development of assays which can determine the level of microcompetition in a cell and to select compounds to target this microcompetition syndrome. In addition, methods to treat a patient for microcompetition based disease are taught. Excerpt(s): The invention pertains to the field of human diseases. More particularly, the invention pertains to how microcompetition for transcription factors contributes to obesity, cancer, atherosclerosis, osteoarthritis, hypertension and diabetes. The cause of many cases of obesity, cancer, atherosclerosis, osteoarthritis, and diabetes is unknown. Therefore, treatment is focused on symptomolgy and effects of the diseases and has limited effectiveness. In many cases, known treatments are associated with serious negative side effects. Recently, the National Cancer Institute (NIH Guide 2000) announced a program aimed to "reorganize the `front-end` or gateway to drug discovery." The new approach promotes a three stage discovery process. The first stage is discovery of the molecular mechanisms that underlie neoplastic transformations, cancer growth and metastasis. Next stage is selection of a novel molecular target within the discovered biochemical pathway known to have a unique difference between a healthy and a cancerous cell. The final stage is design of new drugs that modify the selected target. The program encourages moving away from screening agents by their clinical effects, such as shrinking tumor cells, in vivo or in vitro, to screening agents or designing drugs by their effects on a specific molecular mechanism. According to the NCI, screening by clinical effects identified drugs that demonstrated clear limitations in clinical efficacy, while screening by desired molecular effects should produce more efficaious and specific drugs. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Microprocessor system for the simplified diagnosis of sleep apnea Inventor(s): Lynn, Eric N.; (Columbus, OH), Lynn, Lawrence A.; (Columbus, OH) Correspondence: Lawrence A. Lynn; 1507 Chambers Rd.; Columbus; OH; 43212; US Patent Application Number: 20020173707 Date filed: April 24, 2002 Abstract: A method of evaluating a patient with sleep apnea includes monitoring a patient to produce at least one timed waveform of at least one physiologic parameter, identifying along the waveform a first waveform variation indicative of an apnea, identifying along the waveform a second waveform variation indicative of another apnea, determining the interval intermediate at least one portion of the first waveform variation and at least one portion of the second waveform, and assessing the severity of sleep apnea based on at least the determining. A device for determining the severity of sleep apnea comprises a monitor capable of generating a signal indicative of at least one physiologic parameter and a processor capable of processing the signal, the processor operating to generate a timed waveform of the parameter and to identify a plurality of sequential waveform variations indicative of a corresponding plurality of sequential apneas, the sequential waveform variations having temporal and spatial relationships between the waveform variations and along the waveform, the processor further operating to determine at least one of the temporal and the spatial relationships and displaying the determining so that the determining can be used to assess the severity of sleep apnea. Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/052,438, filed Jul. 14, 1997, the contents of which are hereby incorporated herein by reference and the benefit of U.S. Provisional Application No. 60/052,439, filed Jul. 14, 1997, the contents of which are hereby incorporated herein by reference. This application is a continuation-in-part of U.S. application Ser. No. 08/789,460, filed Jan. 27, 1997, which is a continuation of U.S. patent application Ser. No. 08/391,811, filed Feb. 21, 1995, now U.S. Pat. No. 5,605,151, which is a continuation of U.S. patent application Ser. No. 08/151,901 filed Nov. 15, 1993, now U.S. Pat. No. 5,398,682, which is a continuation-in-part of U.S. patent application Ser. No. 08/931,976, filed Aug. 19, 1992, now abandoned. The contents of application Ser. Nos. 08/789,460, 08/391,811, 08/151,901, 08/931,976, and PCT/US 93/97726, and of U.S. Pat. Nos. 5,605,151 and 5,398,682 are all hereby incorporated herein by reference, the contents of which are incorporated herein by reference. Obstructive Sleep Apnea is now recognized as one of the most common disorders in the US. The lower oxygen levels associated with Obstructive Sleep Apnea is now known to be a major cause of cardiovascular morbidity including heart attack and stroke. A crisis exists in the U.S. in that traditional expensive polysomnography cannot be used to identify these patients on a sufficient scale. The situation is analogous to having a disease as common and subtle as insulin dependent diabetes without an inexpensive and widely implementable and simple mechanism to diagnose the disorder (such as exists for diabetes). Millions of patients remain undiagnosed. The development of a diagnostic system which can allow simplified diagnosis of obstructive sleep apnea by the primary care physician is a national healthcare priority of substantial scale. The prevention of hundreds of thousands of annual excess deaths, stroke and heart attacks associated with obstructive sleep apnea through simplified recognition of this disorder is the most important purpose of the present invention. These excess deaths are occurring annually in a great part due to the lack of availability of this technology resulting in a vast pool of undiagnosed cases of Sleep Apnea. Despite the fact that obstructive sleep apnea is easily treated, both the

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patient and the family are often completely unaware of the presence of this dangerous disease, thinking the patient just a "heavy snorer". Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Mouthpiece, nasal seal, head appliance, apparatus, and methods of treating sleep apnea Inventor(s): Klemperer, Walter G.; (Champaign, IL) Correspondence: Frank S. Rosenberg; 18 Echo Hill Lane; Moraga; CA; 94556; US Patent Application Number: 20030183227 Date filed: March 26, 2002 Abstract: A CPAP device and a method for treating sleep apnea use a head appliance with an oral adaptor comprising a tube partially inserted in a person's mouth and a diaphragm applied over the tube against the mouth, such that the lips are formed into a tight seal with the tube. A nasal seal is described comprising two rollers to which a strap is attached, so that the nasal seal is easily put in place, adjusted and maintained by rolling the rollers on the nose sides or pulling the straps. Excerpt(s): Sleep apnea is a common sleep ailment that affects as many as five percent of the population worldwide. Persons with sleep apnea stop breathing for short durations many times during sleep, so that the depth and quality of their sleep is reduced. As a result, persons with sleep apnea suffer from a profound sleepiness, which can impair their ability and performance at work and in other activities. Sleep apnea often results from a collapse of the person's throat tissues during sleep, which reduces or suppresses the air flow to the lungs. Lowered oxygen levels and increased carbon dioxide levels in blood alert the person's brain and breathing resumes, but each occurrence arouses the person and interrupts restorative sleep. Surgery is a possible treatment but surgical procedures are complex and success rates are often low. A more common treatment for sleep apnea is to force air inside the person's throat during sleep with a respirator apparatus. Apparatuses of this type use continuous positive airway pressure or CPAP. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Multipurpose device for preventing and treating snoring and sleep apnea and /or preventing gnashing of teeth Inventor(s): Alekseevich, Ryazanov Evgeniy; (Moscow, RU), Ivanovich, Bredov Vladimir; (Moscow, RU) Correspondence: McDERMOTT, WILL & EMERY; 600 13th Street, N.W.; Washington; DC; 20005-3096; US Patent Application Number: 20020144685 Date filed: March 22, 2002 Abstract: The invention pertains to the medical devices and may be used as the method for prophylaxis and treating snoring and sleep apnea, and also for preventing gnashing of teeth during a sleep. The device contains joined through the connecting element the cup-shaped fixture and outer and inner restrictive petals with the holes. The petals are set up on the connecting element with an opportunity of moving along it and fixing on it.The cup-shaped fixture has the section in the form of the arc in the surface of the

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longitudinal axis section of the connecting element in the area of its adjoining to the fixture, symmetrical to the planes of the petals of the fixture, and the section in the form of the parabola in the surface of the axis section, perpendicular to the identified. Excerpt(s): The invention pertains to medical devices and is intended for treating snoring, sleep apnea syndrome (short pauses in breathing during a sleep), and also for preventing gnashing of teeth during a sleep. During a sleep a human often can produce non-articulate sounds called snoring, caused by resonant vibrations during the oral cavity tissues and airflow interaction, when the airflow is going through between the palatine curtain and the tongue, and also between the route of the tongue and the posterior wall of the larynx. In the first case these sounds are caused most often by hypotonia of the muscles of the palatine curtain, in the second case, by tongue retraction. Snoring sleep apnea is of great discomfort for the people around and for the snoring person it leads to appearing and developing of different diseases caused by breathing impairment. Sleep apnea can continue from several seconds to two minutes, the total time of such apneas may reach 4 hours during the night. The sequels of the multiple stops of breathing are blood and tissue gas disturbances (less saturation by oxygen) and of oxidation-reduction reactions in the tissues and organs of the organism. As a result those who snore do not have a good sleep and experience some sorts of malaise during the day. 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 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

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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 •

Pharmacological treatment for sleep apnea Inventor(s): Carley, David W.; (Evanston, IL), Radulovacki, Miodrag; (Chicago, IL) Correspondence: MARSHALL, GERSTEIN & BORUN; 6300 SEARS TOWER; 233 SOUTH WACKER; CHICAGO; IL; 60606-6357; US Patent Application Number: 20030130266 Date filed: October 31, 2002 Abstract: The present invention relates generally to pharmacological methods for the prevention of amelioration of sleep-related breathing disorders via administration of agents or combinations of agents that possess serotonin-related pharmacological activity. Excerpt(s): Priority is claimed to U.S. patent application Ser. No. 10/016,901, filed Dec. 14, 2001, which claims priority to U.S. patent application Ser. No. 09/622,823, filed Aug. 23, 2000, now U.S. Pat. No. 6,331,536 issued Dec. 18, 2001, which claims priority International Patent Appl. No. PCT/US99/04347, filed Feb. 26, 1999, which claims priority to U.S. Provisional Pat. App. Ser. No. 60/076,216, all of which are incorporated herein by reference in their entirety. This invention generally relates to methods for the pharmacological treatment of breathing disorders and, more specifically, to the administration of agents or compositions having serotonin-related receptor activity for the alleviation of sleep apnea (central and obstructive) and other sleep-related breathing disorders. Over the past several years much effort has been devoted to the study of a discrete group of breathing disorders that occur primarily during sleep with consequences that may persist throughout the waking hours in the form of sleepiness, thereby manifesting itself into substantial economic loss (e.g., thousands of lost manhours) or employment safety factors (e.g., employee non-attentiveness during operation of heavy-machinery). Sleep-related breathing disorders are characterized by repetitive reduction in breathing (hypopnea), periodic cessation of breathing (apnea), or a continuous or sustained reduction in ventilation.

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Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

RESPIRATORY-ANALYSIS SYSTEMS Inventor(s): BRYDON, JOHN WILLIAM ERNEST; (NEW SOUTH WALES, AU) Correspondence: PILLSBURY WINTHROP LLP; 1600 TYSONS BLVD; MCLEAN; VA; 22102; US Patent Application Number: 20030045806 Date filed: April 20, 2000 Abstract: A movement sensitive mattress (2) is disclosed that has a plurality of independent like movement sensors (5) for measuring movement at different locations on the mattress to generate a plurality of movement signals. The signals are processed to derive respiratory variables including rate, phase, maximum effort and heartrate. Such variables can be combined to derive one or more diagnostic variables including apnea and laboured breathing classifications. Excerpt(s): The invention relates to respiratory-analysis mattresses and systems, and to methods of use thereof. The invention further relates to the measurement of respiratory. cardiac and other movement related functions in patients suffering from a range of respiratory syndromes, including the disordered breathing associated with Cheyne Stokes syndrome, anaesthetic induced partial respiratory obstruction and sleep apnea. Sleep apnea is a respiratory syndrome known to be present in about 8% of the adult male human population and 4% of the adult female human population. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Sleep apnea device and method thereof Inventor(s): Wyckoff, Robert; (Smith River, CA) Correspondence: MYERS & KAPLAN, INTELLECTUAL; PROPERTY LAW, L.L.C.; 1827 POWERS FERRY ROAD; BUILDING 3, SUITE 200,; ATLANTA; GA; 30339; US Patent Application Number: 20030167018 Date filed: March 4, 2002 Abstract: A neck-worn device and a method thereof, wherein a plate having a generally arcuate configuration is placed securely and removably on the neck of a user, wherein a substantially airtight zone is created between the device and the neck of a user, and wherein a valve is provided to allow the escape of air from the airtight zone in response to soft neck tissue respiratory movements, thus enabling the creation of a negative pressure or vacuum and thereby effectively drawing open the air passages of a user. The present invention is particularly suited for, although not limited to, utilization as a sleep apnea device enabling a user to alleviate the bothersome and potentially detrimental effects of sleep apnea without utilizing costly equipment requiring electrical or battery power. Excerpt(s): The present invention relates generally to air pathway clearance devices and, more specifically, to a neck-worn device and a method thereof, wherein a generally negative pressure is created on the exterior surface of a user's neck, thereby effectively holding open the air pathways. The present invention is particularly suited for, although not limited to, utilization as a sleep apnea device enabling a user to alleviate the

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bothersome and potentially detrimental effects of sleep apnea without utilizing costly equipment requiring electrical or battery power. Sleep apnea affects millions of individuals, causing each to experience a variety of symptoms while sleeping. These symptoms often decrease feelings of restfulness and reduce health benefits derived from adequate rapid eye movement (rem) sleep sessions. While the degree of effect varies between individuals, most sleep apnea sufferers with obstructive sleep apnea experience collapse and closure of the soft tissues which form the anterior and lateral walls of the pharynx causing erratic cessations of natural breathing cycles and airflow, disruptive snoring behaviors and drops in oxygen saturation, potentially leading to periodic stoppages and/or interruptions of heart rhythms and blood flow, increased cardiovascular disease risk, hypertension, and in extreme cases, even death. The most popular, presently available, non-surgical treatment method for sleep apnea relies on an electrical instrument, or Continuous Positive Airway Pressure (CPAP) machine. The basic premise behind the CPAP machine and its ability to counteract the affects of sleep apnea rests in the creation of a closed respiratory system for the user, wherein a generally constant and positive pressure forces the airways to remain open. This closed, positive pressure system utilizes a powered generator to blow a stream of air into the user's face through a mask typically worn over the users nose. The complexity of the electronic CPAP instrument makes the device costly to purchase, thus eliminating its availability to many sleep apnea sufferers. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Sleep apnea risk evaluation Inventor(s): Berka, Chris; (Carlsbad, CA), Cvetinovic, Milenko; (Vista, CA), Furman, Yury; (Los Angeles, CA), Levendowski, Daniel J.; (Carlsbad, CA), Westbrook, Philip R.; (Newport Beach, CA) Correspondence: David A. Hall; Heller Ehrman White & McAuliffe LLP; 6th Floor; 4350 La Jolla Village Drive; San Diego; CA; 92122-1246; US Patent Application Number: 20020165462 Date filed: December 28, 2001 Abstract: In a technique for collecting and analyzing physiological signals to detect sleep apnea, a small light-weight physiological monitoring system, affixed to a patient's forehead, detects and records the pulse, oximetry, snoring sounds, and head position of a patient to detect a respiratory event, such as sleep apnea. The physiological monitoring system may contain several sensors including a pulse oximeter to detect oximetry and pulse rate, a microphone to detect snoring sounds, and a position sensor to detect head position. The physiological monitoring system also can contain a memory to store or record the signals monitored by the mentioned sensors and a power source. The physiological monitoring system may be held in place by a single elastic strap, thereby enabling a patient to use the system without the assistance of trained technicians. Excerpt(s): This invention relates generally to the acquisition of physiological data for health signs monitoring and, more particularly, for the diagnosis and treatment of sleep disorders. Sleep apnea (SA) is the most common disorder observed in the practice of sleep medicine and is responsible for more mortality and morbidity than any other sleep disorder. SA is characterized by recurrent failures to breathe adequately during sleep (termed apneas or hypopneas) as a result of obstructions in the upper airway. Apnea is typically defined as a complete cessation of airflow. Hypopnea is typically defined as a

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reduction in airflow disproportionate to the amount of respiratory effort-expended and/or insufficient to meet the individual's metabolic needs. During an apnea or hypopnea, commonly referred to as a respiratory event, oxygen levels in the brain decrease, while the carbon dioxide (CO2) levels rise, causing the sleeper to awaken. The heart beats rapidly and blood pressure rises to high levels (up to 300 mm Hg). The brief arousals to breathe are followed by a return to sleep, but the apneas may recur over 60 times per hour in severe cases. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Sleep apnea therapy device using dynamic overdrive pacing Inventor(s): Bornzin, Gene A.; (Simi Valley, CA), Falkenberg, Eric; (Simi Valley, CA), Levine, Paul A.; (Santa Clarita, CA), Park, Euljoon; (Stevenson Ranch, CA) Correspondence: PACESETTER, INC.; 15900 Valley View Court; Sylmar; CA; 913929221; US Patent Application Number: 20030153954 Date filed: February 14, 2002 Abstract: A cardiac stimulation device uses dynamic overdrive pacing to prevent sleep apnea. In another aspect, the device can use dynamic overdrive pacing to terminate sleep apnea after detection. An implantable cardiac stimulation device comprises a sensor and one or more pulse generators. The sensor senses intrinsic cardiac electrical phenomena. The pulse generators can generate cardiac pacing pulses with timing based on the sensed intrinsic cardiac electrical phenomena to dynamically overdrive the intrinsic cardiac electrical phenomena. The timed cardiac pacing pulses can prevent a sleep apnea condition. Excerpt(s): This application is related to copending, commonly-assigned U.S. patent application Ser. No.______, titled CARDIAC STIMULATION DEVICE INCLUDING SLEEP APNEA PREVENTION AND TREATMENT; and U.S. patent application Ser. No.______, tilted STIMULATION DEVICE FOR SLEEP APNEA PREVENTION, DETECTION AND TREATMENT; both applications filed concurrently herewith. The present invention relates to techniques for providing therapy to patients who suffer from sleep apnea. Sleep apnea is the cessation of breathing for a short time while sleeping. Sleep apnea has multiple classifications based on source of dysfunction. Obstructive sleep apnea results from mechanical blockage of the airway, for example due to weight of fatty neck tissue compressing the trachea. Central sleep apnea results from neurological dysfunction. Mixed sleep apnea has a combination of mechanical and neurological cause. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Sleeping pad, bedding and bumpers to improve respiratory efficiency and environmental temperature of an infant and reduce the risks of sudden infant death syndrome (SIDS) and asphyxiation Inventor(s): Koenig, J. Frank; (Vienna, VA) Correspondence: SHLESINGER, ARKWRIGHT & GARVEY LLP; 3000 South Eads Street; Arlington; VA; 22202; US Patent Application Number: 20020178500 Date filed: July 31, 2002 Abstract: Rebreathing carbon dioxide and overheating of the infant are contributing causes of Sudden Infant Death Syndrome (SIDS) and asphyxiation. The characteristics of conventional crib mattresses, bedding and bumper pads contribute to rebreathing of carbon dioxide and overheating of the infant and may be contributing environmental causes of SIDS, asphyxiation, apnea syndromes and hypoventilation. The present invention consists of improved sleeping pads, beddings and bumper pads which reduce rebreathing of carbon dioxide and overheating and provide increased crib ventilation to stimulate breathing. Excerpt(s): This application is a continuation of U.S. application Ser. No. 09/560,139, filed Apr. 28, 2000, which is a continuation-in-part of U.S. application Ser. No. 08/551,319, filed Nov. 1, 1995, and each of which is incorporated herein by reference. The present invention relates to apparatus for reducing the risk of sudden infant death syndrome, asphyxiation, apnea syndrome and hypoventilation through the use of improved sleeping pads, bedding and bumper pads within a crib or the like to improve the respiratory efficiency and environmental temperature of an infant. Sudden infant death syndrome (SIDS) is the leading cause of postneonatal infant death in the United States. About 7,000 deaths occur each year from SIDS. In addition, many infants die each year of asphyxiation while in a crib. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Use of somatostatin receptor agonists in the treatment of human disorders of sleep hypoxia and oxygen deprivation Inventor(s): Young, Charles W.; (New York, NY) Correspondence: FROMMER LAWRENCE & HAUG; 745 FIFTH AVENUE- 10TH FL.; NEW YORK; NY; 10151; US Patent Application Number: 20030083241 Date filed: October 25, 2002 Abstract: The invention relates to a method of treating diverse human disorders that may arise, in part, out of sleep hypoxia and oxygen deprivation occurring in the context of sleep apnea/hypopnea disturbances. The disorders that may be treated by the invention comprise gastroesophageal reflux disease (GERD), asthma-associated gastroesophageal reflux (GER), GER-associated asthma, asthma, cardiomyopathy, cardioarrhythmia, congestive heart failure, sudden infant death syndrome, and diverse neurologic conditions. The mode of treatment uses somatostatin receptor ligands (SstRLs), particularly somatostatin-receptor agonists. The invention concerns the method of treatment utilizing, and compositions comprising SstRLs and somatostatin

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receptor agonists, including agonists of the somatostatin receptor types 2 and 5, particularly, the type 2A receptor (SsR-2A), including octreotide and lanreotide. Excerpt(s): The invention relates to a method of using somatostatin receptor agonists to treat diverse human disorders of sleep hypoxia and oxygen deprivation, including but not limited to: 1) gastroesophageal reflux disease (GERD), asthma-associated gastroesophageal reflux (GER), GER-associated asthma, and asthma; 2) obstructive sleep apnea (OSA), and OSA-associated conditions, including GER, asthma, cardiomyopathy, cardioarrhythmia, congestive heart failure, median nerve compression neuropathy (carpal tunnel syndrome) and cognitive impairment; as well as sleep apnea-associated sudden infant death syndrome (SIDS), 3) central sleep apnea (CSA), as well as CSAassociated conditions, including GER, cardiomyopathy, cardioarrhythmia, congestive heart failure, and cognitive impairment; 4) mixed pattern sleep apneas, including but not limited to post-vascular occlusion sleep apnea, dementia-associated sleep apnea, amyotrophic lateral sclerosis-associated sleep apnea, myasthenia gravis-associated sleep apnea, and alcoholism-related sleep apnea; 5) excess calpain-activation disorders in tissues where the injured cell population expresses somatostatin receptors; including, but not limited to the central nervous system, peripheral nerves, heart, liver, kidney, and gastrointestinal tract. Various documents are cited in this text. Citations in the text can be by way of a citation to a document in the reference list, e.g., by way of an author(s) and document year, whereby full citation in the text is to a document that may or may not also be listed in the reference list. There is no admission that any of the various documents cited in this text are prior art as to the present invention. Any document having as an author or inventor person or persons named as an inventor herein is a document that is not by another as to the inventor of entity herein. All documents cited in this text ("herein cited documents") and all documents cited or referenced in herein cited documents are hereby incorporated herein by reference. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Ventilatory assistance for treatment of cardiac failure and Cheyne-stokes breathing Inventor(s): Berthon-Jones, Michael; (Leonay, AU) Correspondence: Gottlieb, Rackman & Reisman, P.C.; 270 Madison Avenue; New York; NY; 10016-0601; US Patent Application Number: 20030154979 Date filed: February 26, 2003 Abstract: Method and apparatus for the treatment of cardiac failure, Cheyne Stokes breathing or central sleep apnea are disclosed. A subject is provided with ventilatory support, for example positive pressure ventilatory support using a blower and mask. Respiratory airflow is determined. From the respiratory airflow are derived a measure of instantaneous ventilation (for example half the absolute value of the respiratory airflow) and a measure of longterm average ventilation (for example the instantaneous ventilation low pass filtered with a 100 second time constant). A target ventilation is taken as 95% of the longterm average ventilation. The instantaneous ventilation is fed as the input signal to a clipped integral controller, with the target ventilation as the reference signal. The output of the controller determines the degree of ventilatory support. Clipping is typically to between half and double the degree of support that would do all the respirator work. A third measure of ventilation, for example instantaneous ventilation low pass filtered with a time constant of 5 seconds, is

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calculated. Ventilatory support is in phase with the subject's respiratory airflow to the fuzzy extent that this ventilation is above target, and at a preset rate conversely. Excerpt(s): The invention relates to methods and apparatus for the provision of positive pressure ventilatory assistance for patients with cardiac failure or Cheyne-Stokes breathing from any cause, including central sleep apnea, cardiac failure or stroke. In this specification, respiratory airflow is intended to refer to the instantaneous flow of gas into or out of the lungs. The term "average" is intended to mean any measure of central tendency or the result of any low pass filtering operation. Ventilatory support is intended to mean any procedure which has a similar effect as the respiratory muscles, particularly the supply of breathable gas under varying positive pressure to the airway via a nosemask, face mask, endotracheal tube, tracheotomy tube, or the like, but also including other procedures such as negative pressure ventilation, cuirasse, iron lung, external chest compression, or rocking bed ventilation. According to common usage, ventilation can mean either a procedure, as in the expression "positive pressure ventilation", or a measure of average respiratory airflow over a period of time. Instantaneous ventilation is intended to mean the volume inspired over a short period of time less than several seconds. Equally it can be calculated at the volume expired over such a period, or it can be the average of the two. For example, measures of instantaneous ventilation would include half the average of the absolute value of the respiratory airflow, calculated over a time interval short compared with several seconds, or half the absolute value of the respiratory airflow, low pass filtered with a time constant short compared with several seconds. For technical reasons to be explained below in the best embodiment, instantaneous ventilation is taken as half the absolute value of the instantaneous respiratory airflow, is averaged over an arbitrarily short period of time. However, it is not intended that the invention is limited to calculating instantaneous ventilation in this way. The term "varying A inversely with B" is intended in the broad sense of increasing A if B is decreasing, and decreasing A if B is increasing. 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 apnea, 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 “apnea” (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 apnea. You can also use this procedure to view pending patent applications concerning apnea. 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 APNEA Overview This chapter provides bibliographic book references relating to apnea. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on apnea 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 “apnea” (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 apnea: •

Mayo Clinic on High Blood Pressure Source: New York, NY: Kensington Publishing. 1999. 180 p. Contact: Available from Mayo Clinic. 200 First Street, S.W., Rochester, MN 55905. (800) 291-1128 or (507) 284-2511. Fax (507) 284-0161. Website: www.mayo.edu. PRICE: $14.95 plus shipping and handling. ISBN: 1893005011. Summary: This book focuses on what people who have high blood pressure can do to better manage their blood pressure and keep it at a safe level. The book begins with a chapter that explains the basics of blood pressure, how high blood pressure develops, and why it can be harmful. This is followed by a chapter that identifies unmodifiable and modifiable risk factors for high blood pressure. Unmodifiable risk factors include race, age, family history, and gender. Modifiable risk factors include obesity, inactivity, tobacco use, sodium sensitivity, low potassium, excessive alcohol consumption, stress, chronic illness, high cholesterol, diabetes, sleep apnea, and heart failure. Other topics

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addressed in this chapter include secondary high blood pressure and ways of preventing high blood pressure. The third chapter focuses on the diagnosis and treatment of high blood pressure. Topics include measuring blood pressure, receiving a diagnosis, getting a medical evaluation, and deciding on treatment with either medication or lifestyle changes. Subsequent chapters discuss determining a healthy weight, losing weight, becoming more physically active, and eating well using the Dietary Approaches to Stop Hypertension (DASH) plan. The following chapters detail the effects of sodium, tobacco, alcohol, caffeine, and stress on blood pressure. Another chapter focuses on the mode of action and side effects of various medications used in controlling high blood pressure, including diuretics, beta blockers, angiotensinconverting enzyme inhibitors, angiotensin II receptor blockers, calcium antagonists, alpha blockers, central acting agents, and direct vasodilators. Remaining chapters examine factors unique to women, management of high blood pressure among specific populations and groups, treatment of difficult-to-control high blood pressure, management of a hypertensive emergency, and home monitoring of blood pressure. The book also includes a week of menus based on the recommendations of the DASH eating plan. 17 figures. 2 tables. •

Annual Review of Diabetes 2003 Source: Alexandria, VA: American Diabetes Association. 2003. 168 p. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. E-mail: [email protected]. Fax: (770) 4429742. Website: www.diabetes.org. PRICE: $49.95 plus shipping and handling. Summary: This issue of the Annual Review of Diabetes includes twenty research articles in three categories: epidemiology and pathogenesis, treatment, and complications. Specific topics include the rise of childhood type 1 diabetes in the 20th century; immunological markers in the diagnosis and prediction of autoimmune type 1a diabetes; adults with prediabetes; the energy homeostasis system and weight gain; the metabolic syndrome and incidence of type 2 diabetes; the peroxisome proliferator; the use of oral glucose tolerance tests in clinical practice; the economic costs of diabetes in the United States; diet and exercise among adults with type 2 diabetes; trends for achieving weight loss and increased physical activity; postprandial (after a meal) glucose control; strategies for the treatment of dyslipidemia; self-management education of adults with type 2 diabetes and its impact on glycemic control; common drug pathways and interactions; the interactions of prescribed medications and over-thecounter medications; obstructive sleep apnea in patients with diabetes; gestational diabetes and the incidence of type 2 diabetes; glucose monitoring in gestational diabetes; genetic studies of late diabetes complications; and eating disorders in adolescent girls and young adult women with type 1 diabetes. Each article concludes with a list of references.

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Ear, Nose, and Throat Disorders Sourcebook Source: Detroit, MI: Omnigraphics, Inc. 1998. 576 p. Contact: Available from Omnigraphics, Inc. Penobscot Building, Detroit, MI 48226. (800) 234-1340. Fax (800) 875-1340. PRICE: $78.00. ISBN: 0780802063. Summary: This reference book provides information about some of the most common disorders of the ears, nose, and throat. The text describes diseases and their accompanying symptoms, as well as treatment options and current research initiatives. The book's 67 chapters are arranged in six parts: introduction, disorders of the inner and

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outer ear, vestibular disorders, disorders of the nose and sinuses, disorders of the throat, and cancers related to the ears, nose, and throat. Specific disorders and topics include otitis externa, otitis media, allergy, perforated eardrum, cholesteatoma, otosclerosis, tinnitus, hyperacusis, ear surgery, dizziness, BPPV (benign paraoxysmal positional vertigo), labyrinthitis, Meniere's disease, perilymph fistula, sinusitis, rhinitis, antihistamines, nosebleeds, smell and taste problems, sore throats, hoarseness, swallowing disorders, salivary glands, snoring, sleep apnea, spasmodic dysphonia, laryngeal diseases and disorders, smoking cessation, head and neck cancer, cancer of the oral cavity and upper throat, esophageal cancer, and oropharyngeal cancer. Simple line drawings illustrate some of the anatomical concepts discussed. The book also includes a glossary of terms and an annotated directory of organizational resources with addresses, telephone numbers, e-mail addresses, and web site locations.

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 “apnea” at online booksellers’ Web sites, you may discover nonmedical books that use the generic term “apnea” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “apnea” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

30 Years Sleep Apnea Syndrome (Respiration) by G. Barthlen, H. Matthys; ISBN: 3805565836; http://www.amazon.com/exec/obidos/ASIN/3805565836/icongroupinterna

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Apnea Monitoring by Means of Thoracic Impedance Pneumography (1989); ISBN: 0910275882; http://www.amazon.com/exec/obidos/ASIN/0910275882/icongroupinterna

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Control of Breathing During Development: Apnea of the Newborn and Sudden Infant Death Syndrome: Colloquium Nancy-Pone-A-Mousson, France September 7 by Charlotte Catz, et al (1994); ISBN: 3805559755; http://www.amazon.com/exec/obidos/ASIN/3805559755/icongroupinterna

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Coping With Snoring and Sleep Apnea by Jill Eckersley (2003); ISBN: 0859698904; http://www.amazon.com/exec/obidos/ASIN/0859698904/icongroupinterna

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Get It Up! Revealing the Simple Surprising Lifestyle that Causes Migraines, Alzheimer's, Stroke, Glaucoma, Sleep Apnea, Impotence,.and More! by Sydney Ross Singer, Soma Grismaijer (2000); ISBN: 1930858000; http://www.amazon.com/exec/obidos/ASIN/1930858000/icongroupinterna

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Hypersomnia with Periodic Apneas by Elio Lugaresi (1978); ISBN: 0893350362; http://www.amazon.com/exec/obidos/ASIN/0893350362/icongroupinterna

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Medical technology for the neonate : thermoregulation of the neonate--apnea monitoring, ventilatory assist, and transcutaneous gas assessment--emerging technologies; ISBN: 0910275394; http://www.amazon.com/exec/obidos/ASIN/0910275394/icongroupinterna

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Medications for attention disorders (ADHD/ADD) and related medical problems (Tourette's syndrome, sleep apnea, seizure disorders) : a comprehensive handbook by Edna D. Copeland; ISBN: 0929519116; http://www.amazon.com/exec/obidos/ASIN/0929519116/icongroupinterna

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No More Snoring : A Proven Program for Conquering Snoring and Sleep Apnea by Victor Hoffstein (Author), Shirley Linde (Author) (1998); ISBN: 0471243752; http://www.amazon.com/exec/obidos/ASIN/0471243752/icongroupinterna

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Obstructive Sleep Apnea Syndrome: Clinical Research and Treatment by Christian Guilleminault, Markku Partinen (Editor); ISBN: 0881675857; http://www.amazon.com/exec/obidos/ASIN/0881675857/icongroupinterna

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Obstructive Sleep Apnea Syndrome: Diagnosis and Treatment (Continuing Education Program (American Academy of Otolaryngology--Head and Neck Surgery Foundation).) by B. Tucker Woodson, et al (1996); ISBN: 1567720501; http://www.amazon.com/exec/obidos/ASIN/1567720501/icongroupinterna

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Phantom of the Night: Overcoming Sleep Apnea Syndrome and Snoring-Win You Hidden Struggle to Breathe, Sleep, and Live by T. Scott Johnson, et al; ISBN: 1882431022; http://www.amazon.com/exec/obidos/ASIN/1882431022/icongroupinterna

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Phantom of the Night: Overcoming Sleep Apnea Syrdrome and Snoring by T.S. Johnson, Jerry Halberstadt; ISBN: 1882431006; http://www.amazon.com/exec/obidos/ASIN/1882431006/icongroupinterna

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Restless Nights: Understanding Snoring and Sleep Apnea by Peretz Lavie, Anthony Berris (Translator); ISBN: 0300085443; http://www.amazon.com/exec/obidos/ASIN/0300085443/icongroupinterna

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Sleep Apnea and Rhonchopathy: 3rd World Congress on Sleep Apnea and Phonchopathy, Tokyo, September 21-23, 1991 by Kiyoshi Togawa (1993); ISBN: 380555611X; http://www.amazon.com/exec/obidos/ASIN/380555611X/icongroupinterna

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Sleep Apnea Syndromes by Christian Guilleminault, William C. Dement; ISBN: 0471608815; http://www.amazon.com/exec/obidos/ASIN/0471608815/icongroupinterna

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Sleep Apnea Syndromes Proceedings by Christian Guilleminault; ISBN: 0845103016; http://www.amazon.com/exec/obidos/ASIN/0845103016/icongroupinterna

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Sleep Apnea: Implications in Cardiovascular and Cerebrovascular Disease by T. Douglas Bradley (Editor), John S. Floras (Editor); ISBN: 0824702999; http://www.amazon.com/exec/obidos/ASIN/0824702999/icongroupinterna

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Sleep Apnea: Pathogenesis, Diagnosis, and Treatment by Allan I. Pack (Editor); ISBN: 082470312X; http://www.amazon.com/exec/obidos/ASIN/082470312X/icongroupinterna

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Sleep Apnea-The Phantom of the Night: Overcome Sleep Apnea Syndrome and Win Your Hidden Struggle to Breathe, Sleep, and Live by T. Scott Johnson (Author), et al (2003); ISBN: 1882431057; http://www.amazon.com/exec/obidos/ASIN/1882431057/icongroupinterna

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Snoring and Obstructive Sleep Apnea by David N. F. Fairbanks (Editor), et al (2003); ISBN: 0781740797; http://www.amazon.com/exec/obidos/ASIN/0781740797/icongroupinterna

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Snoring and Obstructive Sleep Apnea (1994); ISBN: 0881672971; http://www.amazon.com/exec/obidos/ASIN/0881672971/icongroupinterna

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Snoring and Obstructive Sleep Apnea Syndrome: A Controversial Issue (Orl Nova, 34) by J.-P. Guyot (Editor) (2000); ISBN: 3805571887; http://www.amazon.com/exec/obidos/ASIN/3805571887/icongroupinterna

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Snoring and Sleep Apnea by Sally W. Soest, Ralph A. Pascualy; ISBN: 0963594540; http://www.amazon.com/exec/obidos/ASIN/0963594540/icongroupinterna

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Snoring and Sleep Apnea: Personal and Family Guide to Diagnosis and Treatment by Ralph A. Pascualy, Sally W. Soest (Contributor); ISBN: 0781701368; http://www.amazon.com/exec/obidos/ASIN/0781701368/icongroupinterna

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Snoring and Sleep Apnea: Sleep Well, Feel Better by Ralph, Md Pascualy, et al; ISBN: 1888799293; http://www.amazon.com/exec/obidos/ASIN/1888799293/icongroupinterna

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Snoring Can Kill!!: Discover How Sleep Apnea Can Be Ruining Your Life by Joseph L. Goldstein; ISBN: 0966893956; http://www.amazon.com/exec/obidos/ASIN/0966893956/icongroupinterna

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The Official Patient's Sourcebook on Infantile Apnea by James N. Parker (Editor), Philip M. Parker (Editor) (2002); ISBN: 0597832021; http://www.amazon.com/exec/obidos/ASIN/0597832021/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 “apnea” (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 •

Apnea of prematurity. Author: University of Vermont. Dept. of Pediatrics.; Year: 1977; Columbus, Ohio: Ross Laboratories, 1977

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Continuous positive airway pressure for the treatment of obstructive sleep apnea in adults Author: Handelsman, Harry.; Year: 1956; Rockville, Md.: National Center for Health Services Research and Health Care Technology Assessment, U.S. Dept. of Health and Human Services, Public Health Service, [1987]

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Health care guideline: diagnosis and treatment of obstructive sleep apnea Author: Institute for Clinical Systems Improvement.; Year: 1957; [Bloomington, Minn.]: ICSI, c2003

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In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is currently adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a "Books" button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.

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Infantile apnea and home monitoring: report of a Consensus Development Conference Author: National Institute of Child Health and Human Development (U.S.); Year: 1993; [Bethesda, MD]: U.S. Dept. of Health and Human Services, Public Health Service, National Institutes of Health, [1987]

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Medical devices: underreporting of serious problems with a home apnea monitor: report to the chairman, Subcommittee on Health and the Environment, Committee on Energy and Commerce, House of Representatives. Author: United States. General Accounting Office.; Year: 1984; Washington, D.C.: U.S. General Accounting Office, [1990]

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Sleep apnea: January 1980 through August 1983: 323 citations Author: Kenton, Charlotte.; Year: 1987; [Bethesda, Md.]: U.S. Dept. of Health and Human Services, Public Health Service, National Institutes of Health, 1983

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Sleep apnea and related disorders Author: Block, A. Jay,; Year: 1987; Chicago: Year Book Medical Publishers, c1985

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Sudden infant death syndrome and infantile apnea: medical and psychosocial aspects of management Author: Friedman, Stanford B. (Stanford Barton),; Year: 1986; Thorofare, N.J.: Slack, c1984

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The NAAP handbook of infant apnea and home monitoring. Author: National Association of Apnea Professionals.; Year: 1987; [Waianae, HI]: National Association of

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Treatment of obstructive sleep apnea: a report Author: Australian Health Technology Advisory Committee.; Year: 1990; [Canberra]: National Health and Medical Research Council, [c1993]

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

Respiratory Disorders Source: in Scully, C. and Cawson, R.A. Medical Problems in Dentistry. 4th ed. Woburn, MA: Butterworth-Heinemann. 1998. p. 154-172. Contact: Available from Butterworth-Heinemann. 225 Wildwood Avenue, Woburn, MA 01801-2041. (800) 366-2665 or (781) 904-2500. Fax (800) 446-6520 or (781) 933-6333. E-mail: [email protected]. Website: www.bh.com. PRICE: $110.00. ISBN: 0723610568. Summary: Respiratory disorders are common and may significantly affect dental treatment, especially general anesthesia. Respiratory diseases are often also a contraindication to opioids, benzodiazepines and other respiratory depressants. This chapter on respiratory disorders is from a text that covers the general medical and surgical conditions relevant to the oral health care sciences. Topics include upper respiratory tract viral infections, sinusitis, lower respiratory tract infections, pulmonary tuberculosis, Legionnaire's disease (legionellosis), lung abscess, bronchiectasis, cystic

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fibrosis, chronic obstructive airways diseases, asthma, bronchogenic carcinoma (lung cancer), occupational lung disease, sarcoidosis, postoperative respiratory complications (including aspiration of gastric contents), obstructive sleep apnea syndrome, and respiratory distress syndromes (RDS). For each disease, the authors discuss general aspects, diagnosis and management issues, dental aspects, and patient care strategies. The chapter includes a summary of the points covered. 1 figure. 5 tables. 51 references. •

How Vocal Abilities Can Be Limited by Anatomical Abnormalities and Bodily Injuries Source: in Thurman, L. and Welch, G., eds. Bodymind and Voice: Foundations of Voice Education, Volumes 1-3. 2nd ed. Collegeville, MN: VoiceCare Network. 2000. p. 582-585. Contact: Available from National Center for Voice and Speech (NCVS). Book Sales, 334 Speech and Hearing Center, University of Iowa, Iowa City, IA 52242. Website: www.ncvs.org. PRICE: $75.00 plus shipping and handling. ISBN: 0874141230. Summary: This chapter on anatomical abnormalities and bodily injuries is from a multivolume text that brings a biopsychosocial approach to the study of the voice. The authors use the phrase 'bodyminds' to describe the interrelationship of perception, memory, learning, behavior, and health, as they combine to affect all environmental interactions, adaptations, and learning. The books are written for teachers, voice professionals, people who use their voices on an avocational basis, and interested members of the general public. This chapter notes that malformations of auditory (hearing) and neural vocal anatomy can have genetic sources, and can lead to abnormalities of speaking or singing functions. Insufficient sensorimotor stimulation during late gestation and childhood can result in underdeveloped neural networks, suboptimum neural capabilities, or functional abnormalities that can affect vocal self expression. Bodily injuries of many types and in many different parts of the body also can impact upon voice and speech. Manifestations of injury may be subtle and short lived, or overt and permanent. The chapter covers morphologic voice disorders, including laryngeal webs, congenital anomalies of the vocal tract, obstructive sleep apnea syndrome (OSAS), swollen soft palate, short soft palate, cleft palate, and enlarged turbinates; and injury to vocal skeleton or soft tissues, including trauma to the anterior neck or cervical spine, laryngeal fracture, mandibular (lower jaw) fracture, trauma to the torso, iatrogenic (physician caused) trauma, recurrent laryngeal nerve injury, vocal fold mucosal scarring, intubation injury, and acquired laryngeal webs. 22 references.

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Lungs and Pleura Source: in Daugirdas, J.T. and Ing, T.S., eds. Handbook of Dialysis. 2nd ed. Boston, MA: Little, Brown and Company. 1994. p. 598-603. Contact: Available from Lippincott-Raven Publishers. 12107 Insurance Way, Hagerstown, MD 21740. (800) 777-2295. Fax (301) 824-7390. E-mail: [email protected]. Website: http://www.lrpub.com. PRICE: $37.95. ISBN: 0316173835. Summary: This chapter on complications affecting the lungs and pleura is from a handbook that outlines all aspects of dialysis therapy, emphasizing the management of dialysis patients. Topics include pulmonary edema, pleural effusion, infection, dyspnea during dialysis, respiratory failure due to hyperkalemia, hypophosphatemia, or glucose load, dosages of pulmonary drugs in dialysis patients, and sleep apnea syndrome in dialysis patients. The author presents information in outline form, for easy reference. 17 references.

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How Vocal Abilities Can Be Limited by Non-Infectious Diseases and Disorders of the Respiratory and Digestive Systems Source: in Thurman, L. and Welch, G., eds. Bodymind and Voice: Foundations of Voice Education, Volumes 1-3. 2nd ed. Collegeville, MN: VoiceCare Network. 2000. p. 546-555. Contact: Available from National Center for Voice and Speech (NCVS). Book Sales, 334 Speech and Hearing Center, University of Iowa, Iowa City, IA 52242. Website: www.ncvs.org. PRICE: $75.00 plus shipping and handling. ISBN: 0874141230. Summary: This chapter on noninfectious diseases and disorders of the respiratory and digestive systems is from a multi-volume text that brings a biopsychosocial approach to the study of the voice. The authors use the phrase 'bodyminds' to describe the interrelationship of perception, memory, learning, behavior, and health, as they combine to affect all environmental interactions, adaptations, and learning. The books are written for teachers, voice professionals, people who use their voices on an avocational basis, and interested members of the general public. This chapter describes the effects of smoking and other pollutants, sinusitis and rhinitis, laryngitis, bronchitis and other pulmonary (lung) diseases, the effects of outdoor and indoor air pollution, normal and disordered nasal (nose) conditions, asthma, obstructive sleep apnea, emphysema, and gastroesophageal reflux disease (GERD, the return of stomach acid to the esophagus and larynx). GERD can result in hoarseness, lowering of the average speaking pitch range, increased effort when singing, and a 'tired voice.' Asthma can affect voice primarily by decreasing the ability of the respiratory system to inhale and then pressurize the lung air to create sufficient breathflow between the vocal folds. Asthma symptoms can be triggered by inhalation of allergens or pollutant particles of irritant chemicals, infection, cold air, vigorous exercise, acute neuropsychobiological distress, or even vigorous singing. 68 references.

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Pediatric Phonatory Disorders Source: in Andrews, M.L. Manual of Voice Treatment: Pediatrics Through Geriatrics. 2nd ed. San Diego, CA: Singular Publishing Group, Inc. 1999. p. 151-217. Contact: Available from Singular Publishing Group, Inc. 401 West 'A' Street, Suite 325, San Diego, CA 92101-7904. (800) 521-8545 or (619) 238-6777. Fax (800) 774-8398 or (619) 238-6789. E-mail: [email protected]. Website: www.singpub.com. PRICE: $55.00 plus shipping and handling. ISBN: 1565939880. Summary: This chapter on pediatric phonatory disorders is from a resource book for clinicians and clinicians in training who are treating patients with voice disorders. The chapter offers five sections: preschool children, school age children, pediatric voice problems associated with other conditions (hearing impairment, cerebral palsy, craniofacial dysmorphology, nasal obstruction, obstructive sleep apnea syndrome, trauma, lesions), the voice at puberty, and the treatment of resonance disorders. The chapter discusses the physiologic systems relevant to voice production from a developmental perspective. To emphasize the importance of complete case history information, the relevance of the possible effects on voice of infant airway obstruction and medical and surgical treatments to alleviate it are reviewed. Other topics include the reasons for tracheotomy and possible complications and sequelae of this surgery; the common symptoms of vocal disruption in school age children; hyperfunctional and hypofunctional patterns associated with respiration, phonation, resonance, and psychodynamics; and the importance of explaining the effects of specific voice disorders in children to their parents, teachers, and allied health professionals. 9 figures. 3 tables.

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Voice Surgery Source: in Sataloff, R.T., ed. Professional Voice: The Science and Art of Clinical Care. 2nd ed. San Diego, CA: Singular Publishing Group, Inc. 1997. p. 603-645. Contact: Available from Singular Publishing Group, Inc. 401 West 'A' Street, Suite 325, San Diego, CA 92101-7904. (800) 521-8545 or (619) 238-6777. Fax (800) 774-8398 or (619) 238-6789. E-mail: [email protected]. Website: www.singpub.com. PRICE: $325.00 plus shipping and handling. ISBN: 1565937287. Summary: This chapter, from a book on the clinical care of the professional voice, reviews the current thinking regarding voice surgery. Most surgical procedures for voice disorders can be performed endoscopically, obviating the need for external incisions and minimizing the amount of tissue disruption. The author stresses that, when endoscopic visualization is not adequate because of patient anatomy, disease extent, or other factors, the surgeon should not compromise the results of treatment or risk patient injury by attempting to complete an endoscopic procedure. Topics include patient selection and consent, documentation (preoperative assessment), timing of voice surgery, indirect laryngoscopy, direct laryngoscopy, anesthesia (local and general), instrumentation, laryngeal microsurgery, contact endoscopy, vocal fold cysts, vocal fold polyps, varicosities and ectatic vessels and vocal fold hemorrhage, Reinke's edema, granulomas and vocal process ulcers, papillomas, ventricular fold cysts, epiglottic cysts, laryngoceles, miscellaneous masses, sulcus vocalis, laryngeal webs, bowed vocal folds, presbyphonia, vocal fold paralysis and framework dysfunction, Teflon injection, Gelfoam injection, collagen injection, autologous fat injection, removal of Teflon, thyroplasty, nomenclature, arytenoid adduction or rotation, nerve anastomosis, nerve muscle pedicle surgery, arytenoid reduction for arytenoid dislocation, arytenoidectomy, voice rest, and related surgery, including that for velopharyngeal insufficiency and obstructive sleep apnea syndrome in professional voice users. 31 figures. 1 table. 99 references.

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Oral Cavity, Pharynx and Esophagus Source: in Strome, M.; Kelly, J.H.; Fried, M.P., eds. Manual of Otolaryngology: Diagnosis and Therapy. 2nd ed. Boston, MA: Little, Brown and Company. 1992. p. 137-171. Contact: Available from Little, Brown and Company. 34 Beacon Street, Boston, MA 02108. (800) 759-0190. PRICE: $27.50 plus shipping and handling. ISBN: 0316819689. Summary: This chapter, from a reference manual detailing the essentials of otolaryngology and head and neck surgery, discusses the oral cavity, pharynx, and esophagus. Topics covered include oropharyngeal anatomy; physical examination of the pharynx; infectious pharyngitis, including acute bacterial pharyngotonsillitis, diptheria, infectious mononucleosis, Vincent's angina, candidiasis, syphilis, gonococcal pharyngitis, tuberculosis, viral pharyngitis, lingual tonsillitis, nasopharyngitis, and AIDS; noninfectious etiology, including pemphigus, retropharyngeal abscess, parapharyngeal abscess, and submandibular space abscess (Ludwig's angina); allergic edema; tissue hypertrophy, including adenotonsillar hypertrophy, and obstructive sleep apnea; congenital obstruction, including Pierre-Robin syndrome, Thornwald's bursa or nasopharyngeal cyst, and choanal atresia; cysts and neoplasms; dysphasia; and esophageal disorders. The manual summarizes the signs and symptoms, diagnosis, and treatment for each disease or disorder. 26 references.

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CHAPTER 8. MULTIMEDIA ON APNEA Overview In this chapter, we show you how to keep current on multimedia sources of information on apnea. We start with sources that have been summarized by federal agencies, and then show you how to find bibliographic information catalogued by the National Library of Medicine.

Bibliography: Multimedia on Apnea 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 apnea (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 apnea: •

Advances in diagnosis and treatment of sleep apnea and snoring [videorecording] Source: sponsored by University of Pennyslvania School of Medicine; CMEinfo.com; Year: 2002; Format: Videorecording; [Cherry Hill, N.J.]: CMEinfo.com, 2000

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Apnea in the newborn [videorecording] Source: produced by Medical Educational Resources Program, Indiana University, School of Medicine; Year: 1978; Format: Videorecording; Indianapolis, Ind.: The Program, 1978

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Apnea of the newborn [slide] Source: Michigan Perinatal Education Project; [produced by] University of Michigan Medical Center, Independent Study Unit; Year: 1978; Format: Slide; Ann Arbor: The University: [for loan and sale by its Medical Center Media Library], c1978

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Fundamentals of adult sleep apnea [videorecording] Source: AJN, American Journal of Nursing Company; [presented by] Belson/Hanwright Video [and] Miramar Communications, Inc; Year: 1995; Format: Videorecording; [United States]: Belson/Hanwright Video, c1995

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Infantile apnea & home monitoring [videorecording] Source: with George A. Little; Year: 1987; Format: Videorecording; Secaucus, N.J.: Network for Continuing Medical Education, 1987

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Neonatal problems, apnea [slide]. Year: 1978; Format: Slide; [Birmingham, Ala.]: University of Alabama School of Medicine, University of Alabama in Birmingham, c1978

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Peter: age 2 [videorecording]: in long term care: recurrent apnea and other congenital anomalies Source: Center for Television Studies; Year: 1979; Format: Videorecording; [s.l.]: N. Cohn; [Hunter River, P. E. I.: [for loan or sale by Center for Television Studies], c1979

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Sleep apnea: an overview [videorecording] Source: Ohio State University, College of Medicine; Year: 1977; Format: Videorecording; [Columbus]: The University: [for loan and sale by its Health Services Audiovisual and Television Center], c1977

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Sleep apnea [videorecording] Source: a presentation of Films for the Humanities & Sciences, a presentation of OETA and Medstar Communications, Inc; Year: 1995; Format: Videorecording; Princeton, N.J.: Films for the Humanities & Sciences, c1995

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Sleep apnea [videorecording]: recognition and management Source: Barry S. DiCicco; Year: 1996; Format: Videorecording; Secaucus, N.J.: Network for Continuing Medical Education, c1996

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Sleep apnea syndrome [videorecording] Source: Dept. of Psychiatry and Behavioral Sciences, Stanford University School of Medicine; Year: 1977; Format: Videorecording; [Palo Alto, Calif.]: The University, c1977

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Sudden infant death syndrome [videorecording]: apnea, sleep studies and monitoring, when and why Source: presented by the Department of Pediatrics, Emory University, School of Medicine; Year: 1983; Format: Videorecording; Atlanta, Ga.: Emory Medical Television Network, 1983

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The Sleep apnea hypersomnolence syndrome [videorecording] Source: William Orr; produced by Media and Educational Materials, University of Oklahoma, Health Sciences Center; Year: 1977; Format: Videorecording; Oklahoma City: The Center: [for sale by its Media Productions], c1977

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CHAPTER 9. PERIODICALS AND NEWS ON APNEA Overview In this chapter, we suggest a number of news sources and present various periodicals that cover apnea.

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

Most patients with apnea have periods of stable sleep Source: Reuters Medical News Date: October 03, 2003

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Surgery prolongs survival for patients with obstructive sleep apnea Source: Reuters Medical News Date: September 22, 2003

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CORRECTION: Obstructive sleep apnea may impair insulin sensitivity in obesity Source: Reuters Medical News Date: September 22, 2003

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Treating apnea reverses heart enlargement Source: Reuters Health eLine Date: August 19, 2003

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Sleep apnea-related left ventricular hypertrophy reversed with treatment Source: Reuters Medical News Date: August 19, 2003

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Mandibular advancement device curbs sleep apnea Source: Reuters Medical News Date: July 29, 2003

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Jaw splint curbs sleep apnea Source: Reuters Health eLine Date: July 29, 2003

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Sleep apnea linked to bed-wetting in kids Source: Reuters Health eLine Date: July 04, 2003

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Children with obstructive sleep apnea show distinct pattern of airway motion Source: Reuters Medical News Date: May 05, 2003

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Bristol-Myers to acquire apnea of prematurity drug Source: Reuters Industry Breifing Date: May 02, 2003

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Sleep apnea may stimulate vasoactive hormones that lead to hypertension Source: Reuters Medical News Date: April 18, 2003

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CPAP improves heart failure and sleep apnea in patients with both disorders Source: Reuters Medical News Date: March 26, 2003

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Continuous positive airway pressure effective for sleep apnea Source: Reuters Industry Breifing Date: March 18, 2003

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Mild hyperactivity may stem from sleep apnea Source: Reuters Medical News Date: March 03, 2003

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Asymptomatic left ventricular dysfunction often associated with sleep apnea Source: Reuters Medical News Date: February 11, 2003

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Viasys gets FDA clearance for new sleep apnea system Source: Reuters Industry Breifing Date: January 28, 2003

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Laser-assisted uvulopalatoplasty has moderate impact on obstructive sleep apnea Source: Reuters Industry Breifing Date: January 24, 2003

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Sleep apnea, stuttering may be linked Source: Reuters Health eLine Date: November 19, 2002

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No increase in apnea/bradycardia spells seen after immunization in preemies Source: Reuters Medical News Date: October 21, 2002

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Snoring without apnea increases stroke risk Source: Reuters Medical News Date: October 16, 2002

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Dental side effects seen with use of oral appliances for sleep apnea Source: Reuters Medical News Date: October 10, 2002

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Structural changes in upper airway mucosa observed in obstructive sleep apnea Source: Reuters Medical News Date: September 26, 2002

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Headaches common in sleep apnea patients Source: Reuters Medical News Date: August 16, 2002

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FDA outlines special controls for apnea monitors Source: Reuters Industry Breifing Date: July 16, 2002

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Viasys sleep apnea device gains FDA clearance Source: Reuters Industry Breifing Date: May 28, 2002

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Use of cardiovascular medications high in undiagnosed sleep apnea Source: Reuters Industry Breifing Date: May 27, 2002

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Sleep apnea linked with nonarteritic anterior ischemic optic neuropathy Source: Reuters Medical News Date: May 24, 2002

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Study links sleep apnea with risk of blood clots Source: Reuters Health eLine Date: May 21, 2002

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Israeli study doubts laser surgery for sleep apnea Source: Reuters Health eLine Date: April 15, 2002

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Favorable results of laser surgery for sleep apnea deteriorate with time Source: Reuters Medical News Date: April 15, 2002

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Pediatricians advised to screen children for snoring, sleep apnea Source: Reuters Medical News Date: April 04, 2002

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Upregulation of adhesion molecules may link apnea to cardiovascular morbidity Source: Reuters Medical News Date: April 03, 2002

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Sleep apnea common in men with idiopathic intracranial hypertension Source: Reuters Medical News Date: April 02, 2002

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Doctor should screen kids for snoring, sleep apnea Source: Reuters Health eLine Date: April 01, 2002

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Dental appliance beats surgery for sleep apnea Source: Reuters Health eLine Date: March 27, 2002

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Dental appliances improves sleep apnea index without adverse effects Source: Reuters Medical News Date: March 26, 2002

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Support program increases compliance rates with CPAP for sleep apnea Source: Reuters Medical News Date: March 15, 2002

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Speeding up heartbeat may improve sleep apnea Source: Reuters Health eLine Date: February 06, 2002

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Narrow upper airway may contribute to sleep apnea Source: Reuters Medical News Date: February 06, 2002

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Narrow throat may cause sleep apnea Source: Reuters Health eLine Date: February 06, 2002

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Atrial overdrive pacing reduces sleep apnea episodes in bradycardia patients Source: Reuters Medical News Date: February 06, 2002

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Obstructive sleep apnea linked to peripheral vasoconstriction Source: Reuters Medical News Date: January 28, 2002

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Preeclampsia augments obstructive sleep apnea Source: Reuters Medical News Date: December 17, 2001

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Size of upper airway explains lower prevalence of sleep apnea in women Source: Reuters Medical News Date: November 27, 2001

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Minor orthodontic changes seen with mandibular advancement for sleep apnea Source: Reuters Industry Breifing Date: October 15, 2001

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CPAP improves cardiac function in sleep apnea patients Source: Reuters Medical News Date: October 09, 2001

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Cephalon's Provigil looks promising as adjunct in sleep apnea patients Source: Reuters Industry Breifing Date: October 09, 2001

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Sleep apnea ups risk of postsurgical complication Source: Reuters Health eLine Date: September 25, 2001

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Short trial of CPAP for sleep apnea predicts long-term use Source: Reuters Medical News Date: September 05, 2001

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Sleep apnea-hypopnea linked to elevated VEGF Source: Reuters Medical News Date: August 24, 2001

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

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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 “apnea” (or synonyms).

Newsletters on Apnea Find newsletters on apnea using the Combined Health Information Database (CHID). You will need to use the “Detailed Search” option. To access CHID, go to the following hyperlink: http://chid.nih.gov/detail/detail.html. Limit your search to “Newsletter” and “apnea.” 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.” Type “apnea” (or synonyms) into the “For these words:” box. The following list was generated using the options described above: •

Wake-Up Call: The Wellness Letter for Snoring and Apnea Source: Washington, DC: American Sleep Apnea Association. 1994-. Contact: Available from American Sleep Apnea Association, 2025 Pennsylvania Avenue, NW, Suite 905, Washington, DC 20006. (202) 293-3650, (202) 293-3656 (Fax), [email protected] (Email), http://[email protected] (Website). Free with membership fee of $25.00 to persons living in the U.S.; membership fee is $50.00 for persons living outside the U.S. Summary: This newsletter is intended to keep snorers and sufferers of sleep apnea up to date on the treatment and management of these conditions. A typical issue includes articles on treatment and management, medical complications associated with the disorders (e.g., cardiovascular disease), risk factors for apnea, funding for research, patient advocacy, health policy, and public health campaigns; a question-and-answer column written by a sleep disorders specialist; and information on the activities of the AWAKE (Alert, Well and Keeping Energetic) Network, a nationwide network of mutual help and health awareness groups for individuals who suffer from sleep-disordered breathing.

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

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periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”

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CHAPTER 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 apnea. 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 non-profit 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 apnea. 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 apnea: Bronchodilators, Theophylline •

Systemic - U.S. Brands: Aerolate Sr; Asmalix; Choledyl; Choledyl SA; Elixophyllin; Lanophyllin; Phyllocontin; Quibron-T Dividose; Quibron-T/SR Dividose; Respbid; Slo-Bid Gyrocaps; Slo-Phyllin; Theo-24; Theobid Duracaps; Theochron; Theo-Dur; Theolair; Theolair-SR; Theo-Time; Th http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/201945.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

Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.

Mosby’s Drug Consult Mosby’s Drug Consult database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/. PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee.

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Researching Orphan Drugs Although the list of orphan drugs is revised on a daily basis, you can quickly research orphan drugs that might be applicable to apnea by using the database managed by the National Organization for Rare Disorders, Inc. (NORD), at http://www.rarediseases.org/. Scroll down the page, and on the left toolbar, click on “Orphan Drug Designation Database.” On this page (http://www.rarediseases.org/search/noddsearch.html), type “apnea” (or synonyms) into the search box, and click “Submit Query.” When you receive your results, note that not all of the drugs may be relevant, as some may have been withdrawn from orphan status. Write down or print out the name of each drug and the relevant contact information. From there, visit the Pharmacopeia Web site and type the name of each orphan drug into the search box at http://www.nlm.nih.gov/medlineplus/druginformation.html. You may need to contact the sponsor or NORD for further information. NORD conducts “early access programs for investigational new drugs (IND) under the Food and Drug Administration’s (FDA’s) approval ‘Treatment INDs’ programs which allow for a limited number of individuals to receive investigational drugs before FDA marketing approval.” If the orphan product about which you are seeking information is approved for marketing, information on side effects can be found on the product’s label. If the product is not approved, you may need to contact the sponsor. The following is a list of orphan drugs currently listed in the NORD Orphan Drug Designation Database for apnea: •

Caffeine (trade name: Neocaf) http://www.rarediseases.org/nord/search/nodd_full?code=599

•

Butyrylcholinesterase http://www.rarediseases.org/nord/search/nodd_full?code=688

If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.

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APPENDICES

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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.

NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute12: •

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

•

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

•

National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html

•

National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25

•

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

•

National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm

•

National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375

•

National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/

12

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

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•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html

•

Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm

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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.13 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:14 •

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

•

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

•

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

•

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

•

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

•

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

•

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/

•

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

•

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

•

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

•

MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html

13

Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 14 See http://www.nlm.nih.gov/databases/databases.html.

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•

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

•

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 Combined Health Information Database

A comprehensive source of information on clinical guidelines written for professionals is the Combined Health Information Database. You will need to limit your search to one of the following: Brochure/Pamphlet, Fact Sheet, or Information Package, and “apnea” using the “Detailed Search” option. Go directly to the following hyperlink: 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 the publication date, select “All Years.” Select your preferred language and the format option “Fact Sheet.” Type “apnea” (or synonyms) into the “For these words:” box. The following is a sample result: •

Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults: The evidence report Source: [Rockville, MD]: National Heart, Lung, and Blood Institute. 1998. 228 pp. Contact: Available from National Heart, Lung, and Blood Institute Information Center, P.O. Box 30105, Bethesda, MD 20824-0105. Telephone: (301) 592-8573 / fax: (301) 5928563 / e-mail: [email protected] / Web site: http://www.nhlbi.nih.gov. $8.50; available from the Web site at no charge. Summary: This report provides guidelines for health care professionals on the identification, evaluation, and treatment of overweight and obesity in adults. The objectives of the report are to (1) identify, evaluate, and summarize published information about the assessment and treatment of overweight and obesity; (2) provide evidence-based guidelines for physicians, other health professionals, and health care organizations for the evaluation and treatment of overweight and obesity in adults; and (3) identify areas for future research. The report is divided into the following seven chapters: (1) introduction, (2) background onoverweight and obesity, (3) examination of randomized controlled trial evidence, (4) treatment guidelines, (5) summary of recommendations, (6) future research, and (7) appendices. The appendices include guidelines development methodology; a literature review; a description of evidence; special populations; obesity and sleep apnea; a body mass index chart; practical dietary therapy information; a resource list; and a glossary of terms. Also provided are lists of abbreviations, references, and publications.

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,

15

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

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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 “apnea” (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 18861 240 126 20 7 19254

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 “apnea” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

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 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

The HSTAT URL is http://hstat.nlm.nih.gov/.

19

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. 20 Adapted from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html. 21

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

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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 Apnea In the following section, we will discuss databases and references which relate to the Genome Project and apnea. 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. To search the database, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type “apnea” (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 apnea: •

Apnea, Central Sleep Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?207720

•

Apnea, Central Sleep Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?107640

•

Apnea, Obstructive Sleep Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?107650

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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Glaucoma and Sleep Apnea Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?137763 Genes and Disease (NCBI - Map)

The Genes and Disease database is produced by the National Center for Biotechnology Information of the National Library of Medicine at the National Institutes of Health. This Web site categorizes each disorder by system of the body. Go to http://www.ncbi.nlm.nih.gov/disease/, and browse the system pages to have a full view of important conditions linked to human genes. Since this site is regularly updated, you may wish to revisit it from time to time. The following systems and associated disorders are addressed: •

Cancer: Uncontrolled cell division. Examples: Breast and ovarian cancer, Burkitt lymphoma, chronic myeloid leukemia, colon cancer, lung cancer, malignant melanoma, multiple endocrine neoplasia, neurofibromatosis, p53 tumor suppressor, pancreatic cancer, prostate cancer, Ras oncogene, RB: retinoblastoma, von Hippel-Lindau syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Cancer.html

•

Immune System: Fights invaders. Examples: Asthma, autoimmune polyglandular syndrome, Crohn’s disease, DiGeorge syndrome, familial Mediterranean fever, immunodeficiency with Hyper-IgM, severe combined immunodeficiency. Web site: http://www.ncbi.nlm.nih.gov/disease/Immune.html

•

Metabolism: Food and energy. Examples: Adreno-leukodystrophy, atherosclerosis, Best disease, Gaucher disease, glucose galactose malabsorption, gyrate atrophy, juvenile-onset diabetes, obesity, paroxysmal nocturnal hemoglobinuria, phenylketonuria, Refsum disease, Tangier disease, Tay-Sachs disease. Web site: http://www.ncbi.nlm.nih.gov/disease/Metabolism.html

•

Muscle and Bone: Movement and growth. Examples: Duchenne muscular dystrophy, Ellis-van Creveld syndrome, Marfan syndrome, myotonic dystrophy, spinal muscular atrophy. Web site: http://www.ncbi.nlm.nih.gov/disease/Muscle.html

•

Nervous System: Mind and body. Examples: Alzheimer disease, amyotrophic lateral sclerosis, Angelman syndrome, Charcot-Marie-Tooth disease, epilepsy, essential tremor, fragile X syndrome, Friedreich’s ataxia, Huntington disease, Niemann-Pick disease, Parkinson disease, Prader-Willi syndrome, Rett syndrome, spinocerebellar atrophy, Williams syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Brain.html

•

Signals: Cellular messages. Examples: Ataxia telangiectasia, Cockayne syndrome, glaucoma, male-patterned baldness, SRY: sex determination, tuberous sclerosis, Waardenburg syndrome, Werner syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Signals.html

•

Transporters: Pumps and channels. Examples: Cystic fibrosis, deafness, diastrophic dysplasia, Hemophilia A, long-QT syndrome, Menkes syndrome, Pendred syndrome, polycystic kidney disease, sickle cell

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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

•

Books: Online books, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=books

•

Genome: Complete genome assemblies, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Genome

•

NCBI’s Protein Sequence Information Survey Results: Web site: http://www.ncbi.nlm.nih.gov/About/proteinsurvey/

•

Nucleotide Sequence Database (Genbank): Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Nucleotide

•

OMIM: Online Mendelian Inheritance in Man, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM

•

PopSet: Population study data sets, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Popset

•

ProbeSet: Gene Expression Omnibus (GEO), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo

•

Protein Sequence Database: Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein

•

PubMed: Biomedical literature (PubMed), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed

•

Structure: Three-dimensional macromolecular structures, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure

•

Taxonomy: Organisms in GenBank, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Taxonomy

To access the Entrez system at the National Center for Biotechnology Information, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=genome, and then select the database that you would like to search. The databases available are listed in the drop box next to “Search.” Enter “apnea” (or synonyms) into the search box and click “Go.”

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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 “apnea” (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 apnea 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 apnea. 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 apnea. 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 “apnea”:

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•

Other guides Arrhythmia http://www.nlm.nih.gov/medlineplus/arrhythmia.html Congenital Heart Disease http://www.nlm.nih.gov/medlineplus/congenitalheartdisease.html Heart Attack http://www.nlm.nih.gov/medlineplus/heartattack.html Heart Diseases http://www.nlm.nih.gov/medlineplus/heartdiseases.html Heart Failure http://www.nlm.nih.gov/medlineplus/heartfailure.html Premature Babies http://www.nlm.nih.gov/medlineplus/prematurebabies.html Sleep Apnea http://www.nlm.nih.gov/medlineplus/sleepapnea.html Sleep Disorders http://www.nlm.nih.gov/medlineplus/sleepdisorders.html

Within the health topic page dedicated to apnea, the following was listed: •

General/Overview JAMA Patient Page: Breathing Problems during Sleep Source: American Medical Association http://www.medem.com/medlb/article_detaillb.cfm?article_ID=ZZZWT155MNC &sub_cat=593

•

Treatment Can Anti-Snoring Claims Be Cause for Alarm? Source: Federal Trade Commission http://www.ftc.gov/bcp/conline/pubs/alerts/snorealrt.htm Choosing a Continuous Positive Airway Pressure (CPAP) Source: American Sleep Apnea Association http://www.sleepapnea.org/cpap.htm Choosing a Mask and Headgear Source: American Sleep Apnea Association http://www.sleepapnea.org/mask.htm Considering Surgery for Obstructive Sleep Apnea (OSA)? Source: American Sleep Apnea Association http://www.sleepapnea.org/osa.html Continuous Positive Airway Pressure (CPAP) Source: American Academy of Otolaryngology--Head and Neck Surgery http://www.entnet.org/healthinfo/snoring/cpap.cfm

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Laser Assisted Uvula Palatoplasty (LAUP) Source: American Academy of Otolaryngology--Head and Neck Surgery http://www.entnet.org/healthinfo/snoring/laup.cfm •

Specific Conditions/Aspects Apnea of Prematurity Source: Nemours Foundation http://kidshealth.org/parent/pregnancy_newborn/medical_problems/aop.html Hypersomnia Source: National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/health_and_medical/disorders/hypersomnia.htm Sleep Apnea and Same-Day Surgery Source: American Sleep Apnea Association http://www.sleepapnea.org/sameday.html Sleep Apnea: A Possible Risk Factor for High Blood Pressure Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=HI00017

•

Children Apnea and Your Child Source: Nemours Foundation http://kidshealth.org/parent/general/sleep/apnea.html Having Your Child Evaluated for Obstructive Sleep Apnea Source: American Sleep Apnea Association http://www.sleepapnea.org/child.html

•

From the National Institutes of Health Sleep Apnea Source: National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/health_and_medical/disorders/sleep_apnea.htm

•

Latest News Depression and Sleep Apnea Linked Source: 11/06/2003, United Press International http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_14564 .html

•

Organizations 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/

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National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/ National Sleep Foundation http://www.sleepfoundation.org/ •

Research Breathing Problems during Sleep and Daytime Behavior Problems Source: Nemours Foundation http://kidshealth.org/research/sleep_behavior.html

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

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

•

Fact Sheet: Facts About Apnea and Other Apparent Life-Threatening Events Source: McLean, VA: National Sudden Infant Death Syndrome Resource Center. 1988. 2 p. Contact: Available from National SIDS Resource Center, Suite 450, 2070 Chain Bridge Road, Vienna, VA 22182-2536. (703) 821-8955, (703) 821-2098 (Fax), [email protected] (Email), http://www.circsol.com/sids (Website). Order No. S69. Summary: This fact sheet on apnea and other apparent life-threatening events (ALTEs) defines these conditions and summarizes the current state of understanding of the

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causes, implications, and appropriate management of infants who experience apneic episodes or ALTEs. The fact sheet discusses the relationship between ALTEs and sudden infant death syndrome (SIDS), the incidence of ALTEs in relation to SIDS, the causes of ALTEs, the effectiveness of home monitors in alerting families about ALTE episodes, which ALTE infants should be monitored at home, and whether or not infants outgrow ALTEs. 5 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 “apnea” (or synonyms). The following was recently posted: •

Apnea of prematurity Source: National Association of Neonatal Nurses - Professional Association; 1999; 22 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2147&nbr=1373&a mp;string=apnea

•

Apnea, sudden infant death syndrome, and home monitoring Source: American Academy of Pediatrics - Medical Specialty Society; 2003 April; 4 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3732&nbr=2958&a mp;string=apnea

•

Clinical practice guideline: diagnosis and management of childhood obstructive sleep apnea syndrome Source: American Academy of Pediatrics - Medical Specialty Society; 2002 April; 9 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3205&nbr=2431&a mp;string=apnea

•

Practice parameters for the use of auto-titrating continuous positive airway pressure devices for titrating pressures and treating adult patients with obstructive sleep apnea syndrome Source: American Academy of Sleep Medicine - Professional Association; 2002 March 15; 5 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3181&nbr=2407&a mp;string=apnea 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

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located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database: •

Facts About Sleep Apnea Summary: This brochure discusses sleep apnea 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=411

•

Frequently Asked Questions and SIDS Research Information Summary: These links focus on a number of issues related to Sudden Infant Death Syndrome: smoking, sleep, sleep apnea, and vaccinations. Source: Sudden Infant Death Syndrome Network, Inc. http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7705

•

Lessening the Effects of Sleep Apnea Summary: This consumer health information fact sheet focuses on the treatment possibilities available for people experiencing sleep apnea. Source: American Association for Respiratory Care http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=3860

•

Sleep Changes in Older Adults Summary: Answers to questions about the sleep patterns of the elderly -- including sleep changes; restless legs syndrome; sleep apnea; and solutions to sleeping better. Source: American Academy of Family Physicians http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6161

•

Snoring & Apnea Summary: This consumer health informtion document discusses snoring, obstructive sleep apnea and the advantages of oral appliance therapy to treat sleep apnea. Source: Academy of Dental Sleep Medicine http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=4404

•

Tossing and Turning No More: How to Get a Good Night's Sleep Summary: This consumer health information article discusses sleep disorders -insomnia, sleep apnea (snoring) -- and the effectiveness of various treatment methods including, melatonin. Source: U.S. Food and Drug Administration http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=3587

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The NIH Search Utility The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to apnea. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

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

•

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

•

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

Associations and Apnea The following is a list of associations that provide information on and resources relating to apnea: •

American Sleep Apnea Association Telephone: (202) 293-3650 Fax: (202) 293-3656 Email: [email protected] Web Site: http://www.sleepapnea.org Background: The American Sleep Apnea Association (ASAA) is a not-for-profit, health service organization dedicated to reducing injuries, disabilities, and potentially lifethreatening complications that may be caused by sleep apnea, a condition characterized by breathing difficulties while sleeping. Sleep apnea may occur during childhood and/or adulthood, may be genetic, and/or may occur due to or in association with a number of different underlying disorders. Established in 1990, the Association works to improve the well-being of affected individuals and family members; promotes early diagnosis and appropriate treatment of sleep apnea through innovative efforts to educate the general public and health care professionals; and supports basic research into the causes and treatments of the disorder. The Association also fosters the

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nationwide ASAA A.W.A.K.E. Network, a network of self-help groups that provide additional information and support to individuals affected by sleep apnea. The American Sleep Apnea Association provides educational materials including a videotape, brochures, a regular newsletter, and guidelines to help individuals start local support groups.

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to apnea. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with apnea. 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 apnea. 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 “apnea” (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received your search results, click on the name of the organization for its description and contact information. The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “apnea”. 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,

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select “All Years.” Then, select your preferred language and the format option “Organization Resource Sheet.” Type “apnea” (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 “apnea” (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)

•

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

•

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

•

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

•

California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html

•

California: Gateway Health Library (Sutter Gould Medical Foundation)

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm

•

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

•

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

•

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

•

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

•

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

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•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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•

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

•

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

•

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

•

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

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

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

•

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

•

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

•

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

•

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

•

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

•

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

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

Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •

Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical

•

MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html

•

Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/

•

Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine

251

APNEA DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal fat: Fat (adipose tissue) that is centrally distributed between the thorax and pelvis and that induces greater health risk. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Ablation: The removal of an organ by surgery. [NIH] Abscess: Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. [NIH] Acantholysis: Separation of the prickle cells of the stratum spinosum of the epidermis, resulting in atrophy of the prickle cell layer. It is seen in diseases such as pemphigus vulgaris (see pemphigus) and keratosis follicularis. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] 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] Acoustic: Having to do with sound or hearing. [NIH] Actin: Essential component of the cell skeleton. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adduction: The rotation of an eye toward the midline (nasally). [NIH] 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

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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] Adipose Tissue: Connective tissue composed of fat cells lodged in the meshes of areolar tissue. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [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] Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Age Groups: Persons classified by age from birth (infant, newborn) to octogenarians and older (aged, 80 and over). [NIH] Age of Onset: The age or period of life at which a disease or the initial symptoms or manifestations of a disease appear in an individual. [NIH] Aged, 80 and Over: A person 80 years of age and older. [NIH] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH]

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Airway Obstruction: Any hindrance to the passage of air into and out of the lungs. [NIH] Airway Resistance: Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. [NIH] Aldosterone: (11 beta)-11,21-Dihydroxy-3,20-dioxopregn-4-en-18-al. A hormone secreted by the adrenal cortex that functions in the regulation of electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. [NIH] Alertness: A state of readiness to detect and respond to certain specified small changes occurring at random intervals in the environment. [NIH] Alexia: The inability to recognize or comprehend written or printed words. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alkaline: Having the reactions of an alkali. [EU] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Alveoli: Tiny air sacs at the end of the bronchioles in the lungs. [NIH] Ameliorating: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amphetamines: Analogs or derivatives of amphetamine. Many are sympathomimetics and central nervous system stimulators causing excitation, vasopression, bronchodilation, and to varying degrees, anorexia, analepsis, nasal decongestion, and some smooth muscle relaxation. [NIH] Ampulla: A sac-like enlargement of a canal or duct. [NIH] Amygdala: Almond-shaped group of basal nuclei anterior to the inferior horn of the lateral ventricle of the brain, within the temporal lobe. The amygdala is part of the limbic system. [NIH]

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]

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Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anaesthetic: 1. Pertaining to, characterized by, or producing anaesthesia. 2. A drug or agent that is used to abolish the sensation of pain. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anaplasia: Loss of structural differentiation and useful function of neoplastic cells. [NIH] Anastomosis: A procedure to connect healthy sections of tubular structures in the body after the diseased portion has been surgically removed. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Androgens: A class of sex hormones associated with the development and maintenance of the secondary male sex characteristics, sperm induction, and sexual differentiation. In addition to increasing virility and libido, they also increase nitrogen and water retention and stimulate skeletal growth. [NIH] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anemic: Hypoxia due to reduction of the oxygen-carrying capacity of the blood as a result of a decrease in the total hemoglobin or an alteration of the hemoglobin constituents. [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] Aneurism: A localized abnormal dilatation of a blood vessel filled with fluid or clotted blood, forming a pulsating tumor, and resulting from disease of the vessel wall. [NIH] Aneurysm: A sac formed by the dilatation of the wall of an artery, a vein, or the heart. [NIH] Angina: Chest pain that originates in the heart. [NIH] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels from surrounding tissue to a solid tumor. This is caused by the release of chemicals by the tumor. [NIH] Angiography: Radiography of blood vessels after injection of a contrast medium. [NIH] Angioplasty: Endovascular reconstruction of an artery, which may include the removal of atheromatous plaque and/or the endothelial lining as well as simple dilatation. These are

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procedures performed by catheterization. When reconstruction of an artery is performed surgically, it is called endarterectomy. [NIH] Angiotensin-Converting Enzyme Inhibitors: A class of drugs whose main indications are the treatment of hypertension and heart failure. They exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility. [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] Anomalies: Birth defects; abnormalities. [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] Anterograde: Moving or extending forward; called also antegrade. [EU] Anthropometric measurements: Measurements of human body height, weight, and size of component parts, including skinfold measurement. Used to study and compare the relative proportions under normal and abnormal conditions. [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] 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] 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, second-

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generation) is a diverse group of drugs including some that act specifically on serotonergic systems. [NIH] 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] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Antihypertensive: An agent that reduces high blood pressure. [EU] 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] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Aorta: The main trunk of the systemic arteries. [NIH] Apathy: Lack of feeling or emotion; indifference. [EU] Apnea: A transient absence of spontaneous respiration. [NIH] Apnoea: Cessation of breathing. [EU] Aponeurosis: Tendinous expansion consisting of a fibrous or membranous sheath which serves as a fascia to enclose or bind a group of muscles. [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] Applicability: A list of the commodities to which the candidate method can be applied as presented or with minor modifications. [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] Arrhythmia: Any variation from the normal rhythm or rate of the heart beat. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and

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the capillaries. [NIH] Arteriovenous: Both arterial and venous; pertaining to or affecting an artery and a vein. [EU] Articular: Of or pertaining to a joint. [EU] Artifacts: Any visible result of a procedure which is caused by the procedure itself and not by the entity being analyzed. Common examples include histological structures introduced by tissue processing, radiographic images of structures that are not naturally present in living tissue, and products of chemical reactions that occur during analysis. [NIH] Aspiration: The act of inhaling. [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] 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] Atmospheric Pressure: The pressure at any point in an atmosphere due solely to the weight of the atmospheric gases above the point concerned. [NIH] Atrial: Pertaining to an atrium. [EU] Atrial Fibrillation: Disorder of cardiac rhythm characterized by rapid, irregular atrial impulses and ineffective atrial contractions. [NIH] Atrioventricular: Pertaining to an atrium of the heart and to a ventricle. [EU] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] 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] Auditory: Pertaining to the sense of hearing. [EU] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Autonomic Nervous System: The enteric, parasympathetic, and sympathetic nervous systems taken together. Generally speaking, the autonomic nervous system regulates the

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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] Autosuggestion: Suggestion coming from the subject himself. [NIH] Axonal: Condition associated with metabolic derangement of the entire neuron and is manifest by degeneration of the distal portion of the nerve fiber. [NIH] Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] 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] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [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] Baroreflex: A negative feedback system which buffers short-term changes in blood pressure. Increased pressure stretches blood vessels which activates pressoreceptors (baroreceptors) in the vessel walls. The net response of the central nervous system is a reduction of central sympathetic outflow. This reduces blood pressure both by decreasing peripheral vascular resistance and by lowering cardiac output. Because the baroreceptors are tonically active, the baroreflex can compensate rapidly for both increases and decreases in blood pressure. [NIH]

Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Benign tumor: A noncancerous growth that 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

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causes central nervous system damage acutely and bone marrow damage chronically and is carcinogenic. It was formerly used as parasiticide. [NIH] Benzodiazepines: A two-ring heterocyclic compound consisting of a benzene ring fused to a diazepine ring. Permitted is any degree of hydrogenation, any substituents and any Hisomer. [NIH] Beta blocker: A drug used to slow the heart rate and reduce pressure inside blood vessels. It also can regulate heart rhythm. [NIH] Beta-pleated: Particular three-dimensional pattern of amyloidoses. [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] Bile Pigments: Pigments that give a characteristic color to bile including: bilirubin, biliverdine, and bilicyanin. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] 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] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Bladder: The organ that stores urine. [NIH] Blister: Visible accumulations of fluid within or beneath the epidermis. [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 Flow Velocity: A value equal to the total volume flow divided by the cross-sectional area of the vascular bed. [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.

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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 Volume: Volume of circulating blood. It is the sum of the plasma volume and erythrocyte volume. [NIH] Blood-Brain Barrier: Specialized non-fenestrated tightly-joined endothelial cells (tight junctions) that form a transport barrier for certain substances between the cerebral capillaries and the brain tissue. [NIH] Body Composition: The relative amounts of various components in the body, such as percent body fat. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Body Mass Index: One of the anthropometric measures of body mass; it has the highest correlation with skinfold thickness or body density. [NIH] Bolus: A single dose of drug usually injected into a blood vessel over a short period of time. Also called bolus infusion. [NIH] Bolus infusion: A single dose of drug usually injected into a blood vessel over a short period of time. Also called bolus. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone scan: A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner. [NIH] Bottle Feeding: Use of nursing bottles for feeding. Applies to humans and animals. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Brachial: All the nerves from the arm are ripped from the spinal cord. [NIH] Brachial Plexus: The large network of nerve fibers which distributes the innervation of the upper extremity. The brachial plexus extends from the neck into the axilla. In humans, the nerves of the plexus usually originate from the lower cervical and the first thoracic spinal cord segments (C5-C8 and T1), but variations are not uncommon. [NIH] Bradycardia: Excessive slowness in the action of the heart, usually with a heart rate below 60 beats per minute. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Brain Stem: The part of the brain that connects the cerebral hemispheres with the spinal cord. It consists of the mesencephalon, pons, and medulla oblongata. [NIH]

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Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Breakdown: A physical, metal, or nervous collapse. [NIH] Broadband: A wide frequency range. Sound whose energy is distributed over a broad range of frequency (generally, more than one octave). [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] Bronchiectasis: Persistent abnormal dilatation of the bronchi. [NIH] Bronchiseptica: A small, gram-negative, motile bacillus. A normal inhabitant of the respiratory tract in man, dogs, and pigs, but is also associated with canine infectious tracheobronchitis and atrophic rhinitis in pigs. [NIH] Bronchitis: Inflammation (swelling and reddening) of the bronchi. [NIH] Bronchopulmonary: Pertaining to the lungs and their air passages; both bronchial and pulmonary. [EU] Bronchopulmonary Dysplasia: A chronic lung disease appearing in certain newborn infants treated for respiratory distress syndrome with mechanical ventilation and elevated concentration of inspired oxygen. [NIH] Bruxism: A disorder characterized by grinding and clenching of the teeth. [NIH] Buffers: A chemical system that functions to control the levels of specific ions in solution. When the level of hydrogen ion in solution is controlled the system is called a pH buffer. [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] Bupivacaine: A widely used local anesthetic agent. [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] Bypass: A surgical procedure in which the doctor creates a new pathway for the flow of body fluids. [NIH] Caffeine: A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes smooth muscle, stimulates cardiac muscle, stimulates diuresis, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calcium Channels: Voltage-dependent cell membrane glycoproteins selectively permeable

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to calcium ions. They are categorized as L-, T-, N-, P-, Q-, and R-types based on the activation and inactivation kinetics, ion specificity, and sensitivity to drugs and toxins. The L- and T-types are present throughout the cardiovascular and central nervous systems and the N-, P-, Q-, & R-types are located in neuronal tissue. [NIH] Calpain: Cysteine proteinase found in many tissues. Hydrolyzes a variety of endogenous proteins including neuropeptides, cytoskeletal proteins, proteins from smooth muscle, cardiac muscle, liver, platelets and erythrocytes. Two subclasses having high and low calcium sensitivity are known. Removes Z-discs and M-lines from myofibrils. Activates phosphorylase kinase and cyclic nucleotide-independent protein kinase. [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]

Cannula: A tube for insertion into a duct or cavity; during insertion its lumen is usually occupied by a trocar. [EU] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carbachol: A slowly hydrolyzed cholinergic agonist that acts at both muscarinic and nicotinic receptors. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinogens: Substances that increase the risk of neoplasms in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. [NIH] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]

Cardiac: Having to do with the heart. [NIH] Cardiac arrest: A sudden stop of heart function. [NIH] Cardiac Output: The volume of blood passing through the heart per unit of time. It is usually expressed as liters (volume) per minute so as not to be confused with stroke volume (volume per beat). [NIH] Cardiomyopathy: A general diagnostic term designating primary myocardial disease, often of obscure or unknown etiology. [EU] Cardiopulmonary: Having to do with the heart and lungs. [NIH] Cardiorespiratory: Relating to the heart and lungs and their function. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH]

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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] Cardiovascular System: The heart and the blood vessels by which blood is pumped and circulated through the body. [NIH] Carnitine: Constituent of striated muscle and liver. It is used therapeutically to stimulate gastric and pancreatic secretions and in the treatment of hyperlipoproteinemias. [NIH] Carotid Body: A small cluster of chemoreceptive and supporting cells located near the bifurcation of the internal carotid artery. The carotid body, which is richly supplied with fenestrated capillaries, senses the pH, carbon dioxide, and oxygen concentrations in the blood and plays a crucial role in their homeostatic control. [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] Carpal Tunnel Syndrome: A median nerve injury inside the carpal tunnel that results in symptoms of pain, numbness, tingling, clumsiness, and a lack of sweating, which can be caused by work with certain hand and wrist postures. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Catheterization: Use or insertion of a tubular device into a duct, blood vessel, hollow organ, or body cavity for injecting or withdrawing fluids for diagnostic or therapeutic purposes. It differs from intubation in that the tube here is used to restore or maintain patency in obstructions. [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] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [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 Adhesion: Adherence of cells to surfaces or to other cells. [NIH] Cell Adhesion Molecules: Surface ligands, usually glycoproteins, that mediate cell-to-cell adhesion. Their functions include the assembly and interconnection of various vertebrate systems, as well as maintenance of tissue integration, wound healing, morphogenic movements, cellular migrations, and metastasis. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH]

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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] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Central Nervous System Depressants: A very loosely defined group of drugs that tend to reduce the activity of the central nervous system. The major groups included here are ethyl alcohol, anesthetics, hypnotics and sedatives, narcotics, and tranquilizing agents (antipsychotics and antianxiety agents). [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] 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 Aqueduct: Narrow channel in the mesencephalon that connects the third and fourth ventricles. [NIH] Cerebral Arteries: The arteries supplying the cerebral cortex. [NIH] Cerebral hemispheres: The two halves of the cerebrum, the part of the brain that controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. The right hemisphere controls muscle movement on the left side of the body, and the left hemisphere controls muscle movement on the right side of the body. [NIH] 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]

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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] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Chemoreceptor: A receptor adapted for excitation by chemical substances, e.g., olfactory and gustatory receptors, or a sense organ, as the carotid body or the aortic (supracardial) bodies, which is sensitive to chemical changes in the blood stream, especially reduced oxygen content, and reflexly increases both respiration and blood pressure. [EU] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chest wall: The ribs and muscles, bones, and joints that make up the area of the body between the neck and the abdomen. [NIH] Child Care: Care of children in the home or institution. [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] Choanal Atresia: Congenital bony or membranous occlusion of one or both choanae, due to failure of the embryonic bucconasal membrane to rupture. [NIH] Cholesteatoma: A non-neoplastic keratinizing mass with stratified squamous epithelium, frequently occurring in the meninges, central nervous system, bones of the skull, and most commonly in the middle ear and mastoid region. [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] 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] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH]

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Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Chronic lymphocytic leukemia: A slowly progressing disease in which too many white blood cells (called lymphocytes) are found in the body. [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] Circadian: Repeated more or less daily, i. e. on a 23- to 25-hour cycle. [NIH] Clamp: A u-shaped steel rod used with a pin or wire for skeletal traction in the treatment of certain fractures. [NIH] Cleft Palate: Congenital fissure of the soft and/or hard palate, due to faulty fusion. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]

Clinical series: A case series in which the patients receive treatment in a clinic or other medical facility. [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Clonazepam: An anticonvulsant used for several types of seizures, including myotonic or atonic seizures, photosensitive epilepsy, and absence seizures, although tolerance may develop. It is seldom effective in generalized tonic-clonic or partial seizures. The mechanism of action appears to involve the enhancement of gaba receptor responses. [NIH] Clonic: Pertaining to or of the nature of clonus. [EU] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] Coca: Any of several South American shrubs of the Erythroxylon genus (and family) that yield cocaine; the leaves are chewed with alum for CNS stimulation. [NIH] Cocaine: An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. [NIH] Cochlear: Of or pertaining to the cochlea. [EU] Cochlear Diseases: Diseases of the cochlea, the part of the inner ear that is concerned with hearing. [NIH] Cofactor: A substance, microorganism or environmental factor that activates or enhances the

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action of another entity such as a disease-causing agent. [NIH] Cognition: Intellectual or mental process whereby an organism becomes aware of or obtains knowledge. [NIH] Colitis: Inflammation of the colon. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Collateral Circulation: Maintenance of blood flow to an organ despite obstruction of a principal vessel. Blood flow is maintained through small vessels. [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 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

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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] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computerized axial tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography (CT scan), or computerized tomography. [NIH] Computerized tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized axial tomography (CAT) scan and computed tomography (CT scan). [NIH] Concomitant: Accompanying; accessory; joined with another. [EU] Conduction: The transfer of sound waves, heat, nervous impulses, or electricity. [EU] Confounding: Extraneous variables resulting in outcome effects that obscure or exaggerate the "true" effect of an intervention. [NIH] Congestion: Excessive or abnormal accumulation of blood in a part. [EU] Congestive heart failure: Weakness of the heart muscle that leads to a buildup of fluid in body tissues. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Conscious Sedation: An alternative to general anesthesia in patients for whom general anesthesia is refused or considered inadvisable. It involves the administering of an antianxiety drug (minor tranquilizer) and an analgesic or local anesthetic. This renders the patient free of anxiety and pain while allowing the patient to remain in verbal contact with the physician or dentist. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constitutional: 1. Affecting the whole constitution of the body; not local. 2. Pertaining to the constitution. [EU] Constriction: The act of constricting. [NIH] Constriction, Pathologic: The condition of an anatomical structure's being constricted beyond normal dimensions. [NIH] Consultation: A deliberation between two or more physicians concerning the diagnosis and the proper method of treatment in a case. [NIH]

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Consumption: Pulmonary tuberculosis. [NIH] Continuum: An area over which the vegetation or animal population is of constantly changing composition so that homogeneous, separate communities cannot be distinguished. [NIH]

Contractility: Capacity for becoming short in response to a suitable stimulus. [EU] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Contralateral: Having to do with the opposite side of the body. [NIH] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]

Convulsions: A general term referring to sudden and often violent motor activity of cerebral or brainstem origin. Convulsions may also occur in the absence of an electrical cerebral discharge (e.g., in response to hypotension). [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Cor: The muscular organ that maintains the circulation of the blood. c. adiposum a heart that has undergone fatty degeneration or that has an accumulation of fat around it; called also fat or fatty, heart. c. arteriosum the left side of the heart, so called because it contains oxygenated (arterial) blood. c. biloculare a congenital anomaly characterized by failure of formation of the atrial and ventricular septums, the heart having only two chambers, a single atrium and a single ventricle, and a common atrioventricular valve. c. bovinum (L. 'ox heart') a greatly enlarged heart due to a hypertrophied left ventricle; called also c. taurinum and bucardia. c. dextrum (L. 'right heart') the right atrium and ventricle. c. hirsutum, c. villosum. c. mobile (obs.) an abnormally movable heart. c. pendulum a heart so movable that it seems to be hanging by the great blood vessels. c. pseudotriloculare biatriatum a congenital cardiac anomaly in which the heart functions as a three-chambered heart because of tricuspid atresia, the right ventricle being extremely small or rudimentary and the right atrium greatly dilated. Blood passes from the right to the left atrium and thence disease due to pulmonary hypertension secondary to disease of the lung, or its blood vessels, with hypertrophy of the right ventricle. [EU] Cor pulmonale: Heart disease that results from resistance to the passage of blood through the lungs; it often leads to right heart failure. [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 Arteriosclerosis: Thickening and loss of elasticity of the coronary arteries. [NIH] Coronary Artery Bypass: Surgical therapy of ischemic coronary artery disease achieved by grafting a section of saphenous vein, internal mammary artery, or other substitute between the aorta and the obstructed coronary artery distal to the obstructive lesion. [NIH] Coronary Disease: Disorder of cardiac function due to an imbalance between myocardial function and the capacity of the coronary vessels to supply sufficient flow for normal function. It is a form of myocardial ischemia (insufficient blood supply to the heart muscle) caused by a decreased capacity of the coronary vessels. [NIH] Coronary heart disease: A type of heart disease caused by narrowing of the coronary

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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] Coronary Vessels: The veins and arteries of the heart. [NIH] Corpus: The body of the uterus. [NIH] Corpus Luteum: The yellow glandular mass formed in the ovary by an ovarian follicle that has ruptured and discharged its ovum. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cost-benefit: A quantitative technique of economic analysis which, when applied to radiation practice, compares the health detriment from the radiation doses concerned with the cost of radiation dose reduction in that practice. [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] Craniofacial Abnormalities: Congenital structural deformities, malformations, or other abnormalities of the cranium and facial bones. [NIH] Creatinine: A compound that is excreted from the body in urine. Creatinine levels are measured to monitor kidney function. [NIH] Critical Care: Health care provided to a critically ill patient during a medical emergency or crisis. [NIH] Crowding: Behavior with respect to an excessive number of individuals, human or animal, in relation to available space. [NIH] Cryotherapy: Any method that uses cold temperature to treat disease. [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] Cyst: A sac or capsule filled with fluid. [NIH] Cystathionine beta-Synthase: A multifunctional pyridoxal phosphate enzyme. In the second stage of cysteine biosynthesis it catalyzes the reaction of homocysteine with serine to form cystathionine with the elimination of water. Deficiency of this enzyme leads to hyperhomocysteinemia and homocystinuria. EC 4.2.1.22. [NIH] Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as

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cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] 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] Cytoskeletal Proteins: Major constituent of the cytoskeleton found in the cytoplasm of eukaryotic cells. They form a flexible framework for the cell, provide attachment points for organelles and formed bodies, and make communication between parts of the cell possible. [NIH]

Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [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] Decision Making: The process of making a selective intellectual judgment when presented with several complex alternatives consisting of several variables, and usually defining a course of action or an idea. [NIH] Decompression: Decompression external to the body, most often the slow lessening of external pressure on the whole body (especially in caisson workers, deep sea divers, and persons who ascend to great heights) to prevent decompression sickness. It includes also sudden accidental decompression, but not surgical (local) decompression or decompression applied through body openings. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Deglutition: The process or the act of swallowing. [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,

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hypoglycaemia, fluid, electrolyte, or acid-base imbalances, or hepatic or renal failure. Called also acute confusional state and acute brain syndrome. [EU] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dental Hygienists: Persons trained in an accredited school or dental college and licensed by the state in which they reside to provide dental prophylaxis under the direction of a licensed dentist. [NIH] Dentate Gyrus: Gray matter situated above the gyrus hippocampi. It is composed of three layers. The molecular layer is continuous with the hippocampus in the hippocampal fissure. The granular layer consists of closely arranged spherical or oval neurons, called granule cells, whose axons pass through the polymorphic layer ending on the dendrites of pyramidal cells in the hippocampus. [NIH] Dentists: Individuals licensed to practice dentistry. [NIH] Dentition: The teeth in the dental arch; ordinarily used to designate the natural teeth in position in their alveoli. [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] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diabetic Retinopathy: Retinopathy associated with diabetes mellitus, which may be of the background type, progressively characterized by microaneurysms, interretinal punctuate macular edema, or of the proliferative type, characterized by neovascularization of the retina and optic disk, which may project into the vitreous, proliferation of fibrous tissue, vitreous hemorrhage, and retinal detachment. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diagnostic Services: Organized services for the purpose of providing diagnosis to promote and maintain health. [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] 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]

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Diastole: Period of relaxation of the heart, especially the ventricles. [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] Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive 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] Dilatation: The act of dilating. [NIH] Dilatation, Pathologic: The condition of an anatomical structure's being dilated beyond normal dimensions. [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] Dilator: A device used to stretch or enlarge an opening. [NIH] Dimethyl: A volatile metabolite of the amino acid methionine. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discrimination: The act of qualitative and/or quantitative differentiation between two or more stimuli. [NIH] Dislocation: The displacement of any part, more especially of a bone. Called also luxation. [EU]

Disorientation: The loss of proper bearings, or a state of mental confusion as to time, place, or identity. [EU] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Dissociative Disorders: Sudden temporary alterations in the normally integrative functions of consciousness. [NIH] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Diuresis: Increased excretion of urine. [EU] Diuretic: A drug that increases the production of urine. [NIH] Diving: An activity in which the organism plunges into water. It includes scuba and bell diving. Diving as natural behavior of animals goes here, as well as diving in decompression experiments with humans or animals. [NIH]

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Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] Donepezil: A drug used in the treatment of Alzheimer's disease. It belongs to the family of drugs called cholinesterase inhibitors. It is being studied as a treatment for side effects caused by radiation therapy to the brain. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] Dorsum: A plate of bone which forms the posterior boundary of the sella turcica. [NIH] Dosage Forms: Completed forms of the pharmaceutical preparation in which prescribed doses of medication are included. They are designed to resist action by gastric fluids, prevent vomiting and nausea, reduce or alleviate the undesirable taste and smells associated with oral administration, achieve a high concentration of drug at target site, or produce a delayed or long-acting drug effect. They include capsules, liniments, ointments, pharmaceutical solutions, powders, tablets, etc. [NIH] Down syndrome: A disorder caused by the presence of an extra chromosome 21 and characterized by mental retardation and distinguishing physical features. [NIH] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Duct: A tube through which body fluids pass. [NIH] Duodenum: The first part of the small intestine. [NIH] Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dyslexia: Partial alexia in which letters but not words may be read, or in which words may be read but not understood. [NIH] Dyslipidemia: Disorders in the lipoprotein metabolism; classified as hypercholesterolemia, hypertriglyceridemia, combined hyperlipidemia, and low levels of high-density lipoprotein (HDL) cholesterol. All of the dyslipidemias can be primary or secondary. Both elevated levels of low-density lipoprotein (LDL) cholesterol and low levels of HDL cholesterol predispose to premature atherosclerosis. [NIH] Dysphonia: Difficulty or pain in speaking; impairment of the voice. [NIH]

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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] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Eardrum: A thin, tense membrane forming the greater part of the outer wall of the tympanic cavity and separating it from the external auditory meatus; it constitutes the boundary between the external and middle ear. [NIH] Eating Disorders: A group of disorders characterized by physiological and psychological disturbances in appetite or food intake. [NIH] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] 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] Elasticity: Resistance and recovery from distortion of shape. [NIH] Elastin: The protein that gives flexibility to tissues. [NIH] Electrocardiogram: Measurement of electrical activity during heartbeats. [NIH] Electrocoagulation: Electrosurgical procedures used to treat hemorrhage (e.g., bleeding ulcers) and to ablate tumors, mucosal lesions, and refractory arrhythmias. [NIH] 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] 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] 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] Embolus: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] 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] Endarterectomy:

Surgical

excision,

performed

under

general

anesthesia,

of

the

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atheromatous tunica intima of an artery. When reconstruction of an artery is performed as an endovascular procedure through a catheter, it is called atherectomy. [NIH] 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]

Endometriosis: A condition in which tissue more or less perfectly resembling the uterine mucous membrane (the endometrium) and containing typical endometrial granular and stromal elements occurs aberrantly in various locations in the pelvic cavity. [NIH] Endometrium: The layer of tissue that lines the uterus. [NIH] Endoscope: A thin, lighted tube used to look at tissues inside the body. [NIH] Endoscopic: A technique where a lateral-view endoscope is passed orally to the duodenum for visualization of the ampulla of Vater. [NIH] Endoscopy: Endoscopic examination, therapy or surgery performed on interior parts of the body. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] 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] Endotracheal intubation: Insertion of an airtube into the windpipe. [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] Entorhinal Cortex: Cortex where the signals are combined with those from other sensory systems. [NIH] Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said

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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] 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] Epidural: The space between the wall of the spinal canal and the covering of the spinal cord. An epidural injection is given into this space. [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] Erythrocyte Volume: Volume of circulating erythrocytes. It is usually measured by radioisotope dilution technique. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Esophageal: Having to do with the esophagus, the muscular tube through which food passes from the throat to the stomach. [NIH] Esophagitis: Inflammation, acute or chronic, of the esophagus caused by bacteria, chemicals, or trauma. [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] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Evoked Potentials: The electric response evoked in the central nervous system by stimulation of sensory receptors or some point on the sensory pathway leading from the receptor to the cortex. The evoked stimulus can be auditory, somatosensory, or visual, although other modalities have been reported. Event-related potentials is sometimes used synonymously with evoked potentials but is often associated with the execution of a motor, cognitive, or psychophysiological task, as well as with the response to a stimulus. [NIH] Excipients: Usually inert substances added to a prescription in order to provide suitable consistency to the dosage form; a binder, matrix, base or diluent in pills, tablets, creams, salves, etc. [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]

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Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Expiration: The act of breathing out, or expelling air from the lungs. [EU] Expiratory: The volume of air which leaves the breathing organs in each expiration. [NIH] Expiratory Reserve Volume: The extra volume of air that can be expired with maximum effort beyond the level reached at the end of a normal, quiet expiration. Common abbreviation is ERV. [NIH] Extensor: A muscle whose contraction tends to straighten a limb; the antagonist of a flexor. [NIH]

Extracellular: Outside a cell or cells. [EU] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extraction: The process or act of pulling or drawing out. [EU] Extraocular: External to or outside of the eye. [NIH] Extrapyramidal: Outside of the pyramidal tracts. [EU] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [EU] Facial: Of or pertaining to the face. [EU] Facial Nerve: The 7th cranial nerve. The facial nerve has two parts, the larger motor root which may be called the facial nerve proper, and the smaller intermediate or sensory root. Together they provide efferent innervation to the muscles of facial expression and to the lacrimal and salivary glands, and convey afferent information for taste from the anterior two-thirds of the tongue and for touch from the external ear. [NIH] Facial Nerve Diseases: Diseases of the facial nerve or nuclei. Pontine disorders may affect the facial nuclei or nerve fascicle. The nerve may be involved intracranially, along its course through the petrous portion of the temporal bone, or along its extracranial course. Clinical manifestations include facial muscle weakness, loss of taste from the anterior tongue, hyperacusis, and decreased lacrimation. [NIH] 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] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] 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] Fissure: Any cleft or groove, normal or otherwise; especially a deep fold in the cerebral cortex which involves the entire thickness of the brain wall. [EU] Fistula: Abnormal communication most commonly seen between two internal organs, or between an internal organ and the surface of the body. [NIH] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The

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condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral, anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] Flatus: Gas passed through the rectum. [NIH] Fluoroscopy: Production of an image when X-rays strike a fluorescent screen. [NIH] Flutter: A rapid vibration or pulsation. [EU] Fold: A plication or doubling of various parts of the body. [NIH] Foramen: A natural hole of perforation, especially one in a bone. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Fourth Ventricle: An irregularly shaped cavity in the rhombencephalon, between the medulla oblongata, the pons, and the isthmus in front, and the cerebellum behind. It is continuous with the central canal of the cord below and with the cerebral aqueduct above, and through its lateral and median apertures it communicates with the subarachnoid space. [NIH]

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

Functional Residual Capacity: The volume of air remaining in the lungs at the end of a normal, quiet expiration. It is the sum of the residual volume and the expiratory reserve volume. Common abbreviation is FRC. [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] GABA: The most common inhibitory neurotransmitter in the central nervous system. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gamma-interferon: Interferon produced by T-lymphocytes in response to various mitogens and antigens. Gamma interferon appears to have potent antineoplastic, immunoregulatory and antiviral activity. [NIH]

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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] Gap Junctions: Connections between cells which allow passage of small molecules and electric current. Gap junctions were first described anatomically as regions of close apposition between cells with a narrow (1-2 nm) gap between cell membranes. The variety in the properties of gap junctions is reflected in the number of connexins, the family of proteins which form the junctions. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gas exchange: Primary function of the lungs; transfer of oxygen from inhaled air into the blood and of carbon dioxide from the blood into the lungs. [NIH] Gastric: Having to do with the stomach. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

Gastroesophageal Reflux: Reflux of gastric juice and/or duodenal contents (bile acids, pancreatic juice) into the distal esophagus, commonly due to incompetence of the lower esophageal sphincter. Gastric regurgitation is an extension of this process with entry of fluid into the pharynx or mouth. [NIH] Gastroesophageal Reflux Disease: Flow of the stomach's contents back up into the esophagus. Happens when the muscle between the esophagus and the stomach (the lower esophageal sphincter) is weak or relaxes when it shouldn't. May cause esophagitis. Also called esophageal reflux or reflux esophagitis. [NIH] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gels: Colloids with a solid continuous phase and liquid as the dispersed phase; gels may be unstable when, due to temperature or other cause, the solid phase liquifies; the resulting colloid is called a sol. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Generator: Any system incorporating a fixed parent radionuclide from which is produced a daughter radionuclide which is to be removed by elution or by any other method and used in a radiopharmaceutical. [NIH] Genetic 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]

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Genetic Techniques: Chromosomal, biochemical, intracellular, and other methods used in the study of genetics. [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] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Gestational: Psychosis attributable to or occurring during pregnancy. [NIH] Giant Cells: Multinucleated masses produced by the fusion of many cells; often associated with viral infections. In AIDS, they are induced when the envelope glycoprotein of the HIV virus binds to the CD4 antigen of uninfected neighboring T4 cells. The resulting syncytium leads to cell death and thus may account for the cytopathic effect of the virus. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Gliosis: The production of a dense fibrous network of neuroglia; includes astrocytosis, which is a proliferation of astrocytes in the area of a degenerative lesion. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]

Glossectomy: Amputation of the tongue. [NIH] Glottis: The vocal apparatus of the larynx, consisting of the true vocal cords (plica vocalis) and the opening between them (rima glottidis). [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] Glucose tolerance: The power of the normal liver to absorb and store large quantities of glucose and the effectiveness of intestinal absorption of glucose. The glucose tolerance test is a metabolic test of carbohydrate tolerance that measures active insulin, a hepatic function based on the ability of the liver to absorb glucose. The test consists of ingesting 100 grams of glucose into a fasting stomach; blood sugar should return to normal in 2 to 21 hours after ingestion. [NIH] Glucose Tolerance Test: Determination of whole blood or plasma sugar in a fasting state before and at prescribed intervals (usually 1/2 hr, 1 hr, 3 hr, 4 hr) after taking a specified amount (usually 100 gm orally) of glucose. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]

Glycoprotein: A protein that has sugar molecules attached to it. [NIH]

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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] Gonadorelin: A decapeptide hormone released by the hypothalamus. It stimulates the synthesis and secretion of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the pituitary gland. [NIH] Gonadotropin: The water-soluble follicle stimulating substance, by some believed to originate in chorionic tissue, obtained from the serum of pregnant mares. It is used to supplement the action of estrogens. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Grafting: The operation of transfer of tissue from one site to another. [NIH] Granulomas: Small lumps in tissues caused by inflammation. [NIH] Gravis: Eruption of watery blisters on the skin among those handling animals and animal products. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] 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] 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] 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] Halogens: A family of nonmetallic, generally electronegative, elements of group VIIa of the periodic table. They are all multivalent and have oxidation numbers of -1 (the most common), 1, 3, 5, and 7. [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;

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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 Behavior: Behaviors expressed by individuals to protect, maintain or promote their health status. For example, proper diet, and appropriate exercise are activities perceived to influence health status. Life style is closely associated with health behavior and factors influencing life style are socioeconomic, educational, and cultural. [NIH] Health Policy: Decisions, usually developed by government policymakers, for determining present and future objectives pertaining to the health care system. [NIH] Health Services: Services for the diagnosis and treatment of disease and the maintenance of health. [NIH] Health Status: The level of health of the individual, group, or population as subjectively assessed by the individual or by more objective measures. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Heartbeat: One complete contraction of the heart. [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] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemicrania: An ache or a pain in one side of the head, as in migraine. [NIH] Hemodiafiltration: The combination of hemodialysis and hemofiltration either simultaneously or sequentially. Convective transport (hemofiltration) may be better for removal of larger molecular weight substances and diffusive transport (hemodialysis) for smaller molecular weight solutes. [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] Hemodynamics: The movements of the blood and the forces involved in systemic or regional blood circulation. [NIH] Hemofiltration: Extracorporeal ultrafiltration technique without hemodialysis for treatment of fluid overload and electrolyte disturbances affecting renal, cardiac, or pulmonary function. [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

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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] Hemoglobin C: A commonly occurring abnormal hemoglobin in which lysine replaces a glutamic acid residue at the sixth position of the beta chains. It results in reduced plasticity of erythrocytes. [NIH] Hemoglobinuria: The presence of free hemoglobin in the urine. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]

Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatomegaly: Enlargement of the liver. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Heritability: The proportion of observed variation in a particular trait that can be attributed to inherited genetic factors in contrast to environmental ones. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]

Hippocampus: A curved elevation of gray matter extending the entire length of the floor of the temporal horn of the lateral ventricle (Dorland, 28th ed). The hippocampus, subiculum, and dentate gyrus constitute the hippocampal formation. Sometimes authors include the entorhinal cortex in the hippocampal formation. [NIH] Hirsutism: Excess hair in females and children with an adult male pattern of distribution. The concept does not include hypertrichosis, which is localized or generalized excess hair. [NIH]

Hoarseness: An unnaturally deep or rough quality of voice. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] 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]

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Host: Any animal that receives a transplanted graft. [NIH] Hybridomas: Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure or "monoclonal" antibodies or T-cell products, identical to those produced by the immunologically competent parent, and continually grow and divide as the neoplastic parent. [NIH] Hydrocephalus: Excessive accumulation of cerebrospinal fluid within the cranium which may be associated with dilation of cerebral ventricles, intracranial hypertension; headache; lethargy; urinary incontinence; and ataxia (and in infants macrocephaly). This condition may be caused by obstruction of cerebrospinal fluid pathways due to neurologic abnormalities, intracranial hemorrhages; central nervous system infections; brain neoplasms; craniocerebral trauma; and other conditions. Impaired resorption of cerebrospinal fluid from the arachnoid villi results in a communicating form of hydrocephalus. Hydrocephalus ex-vacuo refers to ventricular dilation that occurs as a result of brain substance loss from cerebral infarction and other conditions. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] 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] Hyperacusis: An abnormally disproportionate increase in the sensation of loudness in response to auditory stimuli of normal volume. Cochlear diseases; vestibulocochlear nerve diseases; facial nerve diseases; stapes surgery; and other disorders may be associated with this condition. [NIH] Hyperalgesia: Excessive sensitiveness or sensibility to pain. [EU] Hyperandrogenism: A state characterized or caused by an excessive secretion of androgens by the adrenal cortex, ovaries, or testes. The clinical significance in males is negligible, so the term is used most commonly with reference to the female. The common manifestations in women are hirsutism and virilism. It is often caused by ovarian disease (particularly the polycystic ovary syndrome) and by adrenal diseases (particularly adrenal gland hyperfunction). [NIH] Hyperbilirubinemia: Pathologic process consisting of an abnormal increase in the amount of bilirubin in the circulating blood, which may result in jaundice. [NIH] Hypercapnia: A clinical manifestation of abnormal increase in the amount of carbon dioxide in arterial blood. [NIH] Hypercholesterolemia: Abnormally high levels of cholesterol in the blood. [NIH] Hyperglycemia: Abnormally high blood sugar. [NIH] Hyperhomocysteinemia: An inborn error of methionone metabolism which produces an excess of homocysteine in the blood. It is often caused by a deficiency of cystathionine beta-

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synthase and is a risk factor for coronary vascular disease. [NIH] Hyperlipidemia: An excess of lipids in the blood. [NIH] Hyperpnea: Increased ventilation in proportion to increased metabolism. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypersensitivity, Immediate: Hypersensitivity reactions which occur within minutes of exposure to challenging antigen due to the release of histamine which follows the antigenantibody reaction and causes smooth muscle contraction and increased vascular permeability. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hypertension, Pulmonary: Increased pressure within the pulmonary circulation, usually secondary to cardiac or pulmonary disease. [NIH] Hyperthermia: A type of treatment in which body tissue is exposed to high temperatures to damage and kill cancer cells or to make cancer cells more sensitive to the effects of radiation and certain anticancer drugs. [NIH] Hypertrichosis: Localized or generalized excess hair. The concept does not include hirsutism, which is excess hair in females and children with an adult male pattern of distribution. [NIH] Hypertriglyceridemia: Condition of elevated triglyceride concentration in the blood; an inherited form occurs in familial hyperlipoproteinemia IIb and hyperlipoproteinemia type IV. It has been linked to higher risk of heart disease and arteriosclerosis. [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] Hyperventilation: A pulmonary ventilation rate faster than is metabolically necessary for the exchange of gases. It is the result of an increased frequency of breathing, an increased tidal volume, or a combination of both. It causes an excess intake of oxygen and the blowing off of carbon dioxide. [NIH] Hypnotherapy: Sleeping-cure. [NIH] Hypnotic: A drug that acts to induce sleep. [EU] Hypnotics and Sedatives: Drugs used to induce drowsiness or sleep or to reduce psychological excitement or anxiety. [NIH] Hypocapnia: Clinical manifestation consisting of a deficiency of carbon dioxide in arterial blood. [NIH] Hypoglossal Nerve: The 12th cranial nerve. The hypoglossal nerve originates in the hypoglossal nucleus of the medulla and supplies motor innervation to all of the muscles of the tongue except the palatoglossus (which is supplied by the vagus). This nerve also contains proprioceptive afferents from the tongue muscles. [NIH] Hypoglycaemia: An abnormally diminished concentration of glucose in the blood, which may lead to tremulousness, cold sweat, piloerection, hypothermia, and headache, accompanied by irritability, confusion, hallucinations, bizarre behaviour, and ultimately, convulsions and coma. [EU] Hypopharynx: The portion of the pharynx between the inferior portion of the oropharynx and the larynx. [NIH] Hypotension: Abnormally low blood pressure. [NIH]

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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] Hypotonia: A condition of diminished tone of the skeletal muscles; diminished resistance of muscles to passive stretching. [EU] Hypoventilation: A reduction in the amount of air entering the pulmonary alveoli. [NIH] Hypoxemia: Deficient oxygenation of the blood; hypoxia. [EU] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] 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] 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] Illusion: A false interpretation of a genuine percept. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immune Sera: Serum that contains antibodies. It is obtained from an animal that has been immunized either by antigen injection or infection with microorganisms containing the antigen. [NIH] Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Impotence: The inability to perform sexual intercourse. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incompetence: Physical or mental inadequacy or insufficiency. [EU] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence)

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or the escape of stool from the rectum (fecal incontinence). [NIH] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Incubation period: The period of time likely to elapse between exposure to the agent of the disease and the onset of clinical symptoms. [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Inertia: Inactivity, inability to move spontaneously. [EU] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] Infant, Newborn: An infant during the first month after birth. [NIH] Infantile: Pertaining to an infant or to infancy. [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]

Infectious Mononucleosis: A common, acute infection usually caused by the Epstein-Barr virus (Human herpesvirus 4). There is an increase in mononuclear white blood cells and other atypical lymphocytes, generalized lymphadenopathy, splenomegaly, and occasionally hepatomegaly with hepatitis. [NIH] 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] Inflammatory bowel disease: A general term that refers to the inflammation of the colon and rectum. Inflammatory bowel disease includes ulcerative colitis and Crohn's disease. [NIH]

Informed Consent: Voluntary authorization, given to the physician by the patient, with full comprehension of the risks involved, for diagnostic or investigative procedures and medical and surgical treatment. [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] Inlay: In dentistry, a filling first made to correspond with the form of a dental cavity and

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then cemented into the cavity. [NIH] Inner ear: The labyrinth, comprising the vestibule, cochlea, and semicircular canals. [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] Inositol: An isomer of glucose that has traditionally been considered to be a B vitamin although it has an uncertain status as a vitamin and a deficiency syndrome has not been identified in man. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1379) Inositol phospholipids are important in signal transduction. [NIH] Inotropic: Affecting the force or energy of muscular contractions. [EU] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insomnia: Difficulty in going to sleep or getting enough sleep. [NIH] Insulator: Material covering the metal conductor of the lead. It is usually polyurethane or silicone. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Intensive Care: Advanced and highly specialized care provided to medical or surgical patients whose conditions are life-threatening and require comprehensive care and constant monitoring. It is usually administered in specially equipped units of a health care facility. [NIH]

Intensive Care Units: Hospital units providing continuous surveillance and care to acutely ill patients. [NIH] Intercellular Adhesion Molecule-1: A cell-surface ligand with a role in leukocyte adhesion and inflammation. Its production is induced by gamma-interferon and it is required for neutrophil migration into inflamed tissue. [NIH] Intercostal: Situated between the ribs. [EU] Interferometry: Measurement of distances or movements by means of the phenomena caused by the interference of two rays of light (optical interferometry) or of sound (acoustic interferometry). [NIH] Interindividual: Occurring between two or more individuals. [EU] Interleukin-1: A soluble factor produced by monocytes, macrophages, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. IL-1 consists of two distinct forms, IL-1 alpha and IL-1 beta which perform the same functions but are distinct proteins. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. The factor is distinct from interleukin-2. [NIH] Interleukin-2: Chemical mediator produced by activated T lymphocytes and which regulates the proliferation of T cells, as well as playing a role in the regulation of NK cell activity. [NIH] Interleukin-6: Factor that stimulates the growth and differentiation of human B-cells and is also a growth factor for hybridomas and plasmacytomas. It is produced by many different cells including T-cells, monocytes, and fibroblasts. [NIH]

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Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] Intestines: The section of the alimentary canal from the stomach to the anus. It includes the large intestine and small intestine. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intracranial Hypertension: Increased pressure within the cranial vault. This may result from several conditions, including hydrocephalus; brain edema; intracranial masses; severe systemic hypertension; pseudotumor cerebri; and other disorders. [NIH] Intraocular: Within the eye. [EU] Intraocular pressure: Pressure of the fluid inside the eye; normal IOP varies among individuals. [NIH] Intrathecal: Describes the fluid-filled space between the thin layers of tissue that cover the brain and spinal cord. Drugs can be injected into the fluid or a sample of the fluid can be removed for testing. [NIH] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Intubation: Introduction of a tube into a hollow organ to restore or maintain patency if obstructed. It is differentiated from catheterization in that the insertion of a catheter is usually performed for the introducing or withdrawing of fluids from the body. [NIH] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

Involuntary: Reaction occurring without intention or volition. [NIH] 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] Ion Exchange: Reversible chemical reaction between a solid, often an ION exchange resin, and a fluid whereby ions may be exchanged from one substance to another. This technique is used in water purification, in research, and in industry. [NIH] Ionization: 1. Any process by which a neutral atom gains or loses electrons, thus acquiring a net charge, as the dissociation of a substance in solution into ions or ion production by the passage of radioactive particles. 2. Iontophoresis. [EU] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Iontophoresis: Therapeutic introduction of ions of soluble salts into tissues by means of electric current. In medical literature it is commonly used to indicate the process of increasing the penetration of drugs into surface tissues by the application of electric current. It has nothing to do with ion exchange, air ionization nor phonophoresis, none of which requires current. [NIH]

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Irritable Bowel Syndrome: A disorder that comes and goes. Nerves that control the muscles in the GI tract are too active. The GI tract becomes sensitive to food, stool, gas, and stress. Causes abdominal pain, bloating, and constipation or diarrhea. Also called spastic colon or mucous colitis. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Ischemic stroke: A condition in which the blood supply to part of the brain is cut off. Also called "plug-type" strokes. Blocked arteries starve areas of the brain controlling sight, speech, sensation, and movement so that these functions are partially or completely lost. Ischemic stroke is the most common type of stroke, accounting for 80 percent of all strokes. Most ischemic strokes are caused by a blood clot called a thrombus, which blocks blood flow in the arteries feeding the brain, usually the carotid artery in the neck, the major vessel bringing blood to the brain. When it becomes blocked, the risk of stroke is very high. [NIH] Jaundice: A clinical manifestation of hyperbilirubinemia, consisting of deposition of bile pigments in the skin, resulting in a yellowish staining of the skin and mucous membranes. [NIH]

Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] 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] Kinetics: The study of rate dynamics in chemical or physical systems. [NIH] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Labyrinth: The internal ear; the essential part of the organ of hearing. It consists of an osseous and a membranous portion. [NIH] Labyrinthitis: Inflammation of the inner ear. [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] Laryngeal: Having to do with the larynx. [NIH] Laryngeal Diseases: General or unspecified disorders of the larynx. [NIH] Laryngeal Nerves: Branches of the vagus nerve (the tenth cranial nerve). The superior laryngeal nerves originate near the nodose ganglion and separate into external branches, which supply motor fibers to the cricothyroid muscles, and internal branches, which carry sensory fibers. The recurrent (inferior) laryngeal nerve originates more caudally and carries efferents to all muscles of the larynx except the cricothyroid. The laryngeal nerves and their

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various branches also carry sensory and autonomic fibers to the laryngeal, pharyngeal, tracheal, and cardiac regions. [NIH] Laryngitis: Inflammation of the larynx. This condition presents itself with dryness and soreness of the throat, difficulty in swallowing, cough, and hoarseness. [NIH] Laryngoscopy: Examination, therapy, or surgery of the interior of the larynx performed with a specially designed endoscope. [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] Laser Surgery: The use of a laser either to vaporize surface lesions or to make bloodless cuts in tissue. It does not include the coagulation of tissue by laser. [NIH] Latency: The period of apparent inactivity between the time when a stimulus is presented and the moment a response occurs. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Legionellosis: Infections with bacteria of the genus Legionella. [NIH] Leptin: A 16-kD peptide hormone secreted from white adipocytes and implicated in the regulation of food intake and energy balance. Leptin provides the key afferent signal from fat cells in the feedback system that controls body fat stores. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] 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] Leuprolide: A potent and long acting analog of naturally occurring gonadotropin-releasing hormone (gonadorelin). Its action is similar to gonadorelin, which regulates the synthesis and release of pituitary gonadotropins. [NIH] Libido: The psychic drive or energy associated with sexual instinct in the broad sense (pleasure and love-object seeking). It may also connote the psychic energy associated with instincts in general that motivate behavior. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]

Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Ligands: A RNA simulation method developed by the MIT. [NIH] Light microscope: A microscope (device to magnify small objects) in which objects are lit directly by white light. [NIH] Limbic: Pertaining to a limbus, or margin; forming a border around. [EU] Limbic System: A set of forebrain structures common to all mammals that is defined functionally and anatomically. It is implicated in the higher integration of visceral, olfactory, and somatic information as well as homeostatic responses including fundamental survival behaviors (feeding, mating, emotion). For most authors, it includes the amygdala, epithalamus, gyrus cinguli, hippocampal formation (see hippocampus), hypothalamus, parahippocampal gyrus, septal nuclei, anterior nuclear group of thalamus, and portions of

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the basal ganglia. (Parent, Carpenter's Human Neuroanatomy, 9th ed, p744; NeuroNames, http://rprcsgi.rprc.washington.edu/neuronames/index.html (September 2, 1998)). [NIH] Linkages: 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] Lip: Either of the two fleshy, full-blooded margins of the mouth. [NIH] Lipid: Fat. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipoma: A benign tumor composed of fat cells. [NIH] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver scan: An image of the liver created on a computer screen or on film. A radioactive substance is injected into a blood vessel and travels through the bloodstream. It collects in the liver, especially in abnormal areas, and can be detected by the scanner. [NIH] Lobe: A portion of an organ such as the liver, lung, breast, or brain. [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] Locus Coeruleus: Bluish region in the superior angle of the fourth ventricle floor, corresponding to melanin-like pigmented nerve cells which lie lateral to the pontomesencephalic central gray (griseum centrale). It is also known as nucleus pigmentosus pontis. [NIH] Longitudinal study: Also referred to as a "cohort study" or "prospective study"; the analytic method of epidemiologic study in which subsets of a defined population can be identified who are, have been, or in the future may be exposed or not exposed, or exposed in different degrees, to a factor or factors hypothesized to influence the probability of occurrence of a given disease or other outcome. The main feature of this type of study is to observe large numbers of subjects over an extended time, with comparisons of incidence rates in groups that differ in exposure levels. [NIH] Long-Term Potentiation: A persistent increase in synaptic efficacy, usually induced by appropriate activation of the same synapses. The phenomenological properties of long-term potentiation suggest that it may be a cellular mechanism of learning and memory. [NIH] 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] Lordosis: The anterior concavity in the curvature of the lumbar and cervical spine as viewed from the side. The term usually refers to abnormally increased curvature (hollow back, saddle back, swayback). It does not include lordosis as normal mating posture in certain animals ( = posture + sex behavior, animal). [NIH] Low-density lipoprotein: Lipoprotein that contains most of the cholesterol in the blood.

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LDL carries cholesterol to the tissues of the body, including the arteries. A high level of LDL increases the risk of heart disease. LDL typically contains 60 to 70 percent of the total serum cholesterol and both are directly correlated with CHD risk. [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]

Lumen: The cavity or channel within a tube or tubular organ. [EU] Luxation: The displacement of the particular surface of a bone from its normal joint, without fracture. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]

Lymphadenopathy: Disease or swelling of the lymph nodes. [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] Lymphocytic: Referring to lymphocytes, a type of white blood cell. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Lysine: An essential amino acid. It is often added to animal feed. [NIH] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malaise: A vague feeling of bodily discomfort. [EU] Malformation: A morphologic developmental process. [EU]

defect

resulting

from

an

intrinsically

abnormal

Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]

Mammary: Pertaining to the mamma, or breast. [EU] 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] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU]

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Mastication: The act and process of chewing and grinding food in the mouth. [NIH] Maxillary: Pertaining to the maxilla : the irregularly shaped bone that with its fellow forms the upper jaw. [EU] 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] Mechanoreceptors: Cells specialized to transduce mechanical stimuli and relay that information centrally in the nervous system. Mechanoreceptors include hair cells, which mediate hearing and balance, and the various somatosensory receptors, often with nonneural accessory structures. [NIH] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Median Nerve: A major nerve of the upper extremity. In humans, the fibers of the median nerve originate in the lower cervical and upper thoracic spinal cord (usually C6 to T1), travel via the brachial plexus, and supply sensory and motor innervation to parts of the forearm and hand. [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 Oncology: A subspecialty of internal medicine concerned with the study of neoplasms. [NIH] Medical Records: Recording of pertinent information concerning patient's illness or illnesses. [NIH] Medicament: A medicinal substance or agent. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Medullary: Pertaining to the marrow or to any medulla; resembling marrow. [EU] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Melanin: The substance that gives the skin its color. [NIH] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] 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] 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 Fatigue: Fatigue arising in consequence of mental effort. [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] Mesencephalic: Ipsilateral oculomotor paralysis and contralateral tremor, spasm. or choreic movements of the face and limbs. [NIH] Mesenteric: Pertaining to the mesentery : a membranous fold attaching various organs to the body wall. [EU] Mesentery: A layer of the peritoneum which attaches the abdominal viscera to the abdominal wall and conveys their blood vessels and nerves. [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] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] 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] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microcirculation: The vascular network lying between the arterioles and venules; includes capillaries, metarterioles and arteriovenous anastomoses. Also, the flow of blood through this network. [NIH] Microdialysis: A technique for measuring extracellular concentrations of substances in tissues, usually in vivo, by means of a small probe equipped with a semipermeable

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membrane. Substances may also be introduced into the extracellular space through the membrane. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Microsurgery: Surgical procedures on the cellular level; a light microscope and miniaturized instruments are used. [NIH] Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein tubulin. [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] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mobility: Capability of movement, of being moved, or of flowing freely. [EU] 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] 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] 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] Morphology: The science of the form and structure of organisms (plants, animals, and other

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forms of life). [NIH] Motility: The ability to move spontaneously. [EU] Motor Activity: The physical activity of an organism as a behavioral phenomenon. [NIH] Motor Cortex: Area of the frontal lobe concerned with primary motor control. It lies anterior to the central sulcus. [NIH] Motor nerve: An efferent nerve conveying an impulse that excites muscular contraction. [NIH]

Motor Neurons: Neurons which activate muscle cells. [NIH] Mucinous: Containing or resembling mucin, the main compound in mucus. [NIH] Mucociliary: Pertaining to or affecting the mucus membrane and hairs (including eyelashes, nose hair, .): mucociliary clearing: the clearance of mucus by ciliary movement ( particularly in the respiratory system). [EU] Mucosa: A mucous membrane, or tunica mucosa. [EU] Multiple sclerosis: A disorder of the central nervous system marked by weakness, numbness, a loss of muscle coordination, and problems with vision, speech, and bladder control. Multiple sclerosis is thought to be an autoimmune disease in which the body's immune system destroys myelin. Myelin is a substance that contains both protein and fat (lipid) and serves as a nerve insulator and helps in the transmission of nerve signals. [NIH] Multivalent: Pertaining to a group of 5 or more homologous or partly homologous chromosomes during the zygotene stage of prophase to first metaphasis in meiosis. [NIH] Muscle Fibers: Large single cells, either cylindrical or prismatic in shape, that form the basic unit of muscle tissue. They consist of a soft contractile substance enclosed in a tubular sheath. [NIH] Muscle relaxant: An agent that specifically aids in reducing muscle tension, as those acting at the polysynaptic neurons of motor nerves (e.g. meprobamate) or at the myoneural junction (curare and related compounds). [EU] Muscle Relaxation: That phase of a muscle twitch during which a muscle returns to a resting position. [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] Myasthenia: Muscular debility; any constitutional anomaly of muscle. [EU] Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [EU] Myelin: The fatty substance that covers and protects nerves. [NIH] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocardial Ischemia: A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (coronary arteriosclerosis), to obstruction by a thrombus (coronary thrombosis), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result

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in necrosis of cardiac muscle (myocardial infarction). [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myofibrils: Highly organized bundles of actin, myosin, and other proteins in the cytoplasm of skeletal and cardiac muscle cells that contract by a sliding filament mechanism. [NIH] Myopathy: Any disease of a muscle. [EU] Myosin: Chief protein in muscle and the main constituent of the thick filaments of muscle fibers. In conjunction with actin, it is responsible for the contraction and relaxation of muscles. [NIH] Myotonic Dystrophy: A condition presenting muscle weakness and wasting which may be progressive. [NIH] Nadir: The lowest point; point of greatest adversity or despair. [EU] 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] Nasal Cavity: The proximal portion of the respiratory passages on either side of the nasal septum, lined with ciliated mucosa, extending from the nares to the pharynx. [NIH] Nasal Obstruction: Any hindrance to the passage of air into and out of the nose. The obstruction may be in the nasal vestibule, fossae, or other areas of the nasal cavity. [NIH] Nasal Septum: The partition separating the two nasal cavities in the midplane, composed of cartilaginous, membranous and bony parts. [NIH] Nasogastric: The process of passing a small, flexible plastic tube through the nose or mouth into the stomach or small intestine. [NIH] Nasopharyngitis: Inflammation of the nasopharynx. [NIH] Nasopharynx: The nasal part of the pharynx, lying above the level of the soft palate. [NIH] Natriuresis: The excretion of abnormal amounts of sodium in the urine. [EU] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Neocortex: The largest portion of the cerebral cortex. It is composed of neurons arranged in six layers. [NIH]

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Neonatal: Pertaining to the first four weeks after birth. [EU] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Nephrology: A subspecialty of internal medicine concerned with the anatomy, physiology, and pathology of the kidney. [NIH] Nephropathy: Disease of the kidneys. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nerve Endings: Specialized terminations of peripheral neurons. Nerve endings include neuroeffector junction(s) by which neurons activate target organs and sensory receptors which transduce information from the various sensory modalities and send it centrally in the nervous system. Presynaptic nerve endings are presynaptic terminals. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] 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] Neuroeffector Junction: The synapse between a neuron (presynaptic) and an effector cell other than another neuron (postsynaptic). Neuroeffector junctions include synapses onto muscles and onto secretory cells. [NIH] Neuroendocrine: Having to do with the interactions between the nervous system and the endocrine system. Describes certain cells that release hormones into the blood in response to stimulation of the nervous system. [NIH] Neuroendocrinology: The study of the anatomical and functional relationships between the nervous system and the endocrine system. [NIH] Neurogenic: Loss of bladder control caused by damage to the nerves controlling the bladder. [NIH] Neuroglia: The non-neuronal cells of the nervous system. They are divided into macroglia (astrocytes, oligodendroglia, and schwann cells) and microglia. They not only provide physical support, but also respond to injury, regulate the ionic and chemical composition of the extracellular milieu, participate in the blood-brain and blood-retina barriers, form the myelin insulation of nervous pathways, guide neuronal migration during development, and exchange metabolites with neurons. Neuroglia have high-affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitters, but their role in signaling (as in many other functions) is unclear. [NIH] Neurologic: Having to do with nerves or the nervous system. [NIH] Neurology: A medical specialty concerned with the study of the structures, functions, and diseases of the nervous system. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon,

Dictionary 301

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] Neuropeptides: Peptides released by neurons as intercellular messengers. Many neuropeptides are also hormones released by non-neuronal cells. [NIH] Neurophysiology: The scientific discipline concerned with the physiology of the nervous system. [NIH] Neurotoxic: Poisonous or destructive to nerve tissue. [EU] Neurotoxin: A substance that is poisonous to nerve tissue. [NIH] Neurotransmitters: Endogenous signaling molecules that alter the behavior of neurons or effector cells. Neurotransmitter is used here in its most general sense, including not only messengers that act directly to regulate ion channels, but also those that act through second messenger systems, and those that act at a distance from their site of release. Included are neuromodulators, neuroregulators, neuromediators, and neurohumors, whether or not acting at synapses. [NIH] Neutrophil: A type of white blood cell. [NIH] Niacin: Water-soluble vitamin of the B complex occurring in various animal and plant tissues. Required by the body for the formation of coenzymes NAD and NADP. Has pellagra-curative, vasodilating, and antilipemic properties. [NIH] Nicotine: Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]

Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Nocturia: Excessive urination at night. [EU] Nodose: Having nodes or projections. [EU] Nodose Ganglion: The inferior (caudal) ganglion of the vagus (10th cranial) nerve. The unipolar nodose ganglion cells are sensory cells with central projections to the medulla and peripheral processes traveling in various branches of the vagus nerve. [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] Normotensive: 1. Characterized by normal tone, tension, or pressure, as by normal blood pressure. 2. A person with normal blood pressure. [EU]

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Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nurse Practitioners: Nurses who are specially trained to assume an expanded role in providing medical care under the supervision of a physician. [NIH] Observational study: An epidemiologic study that does not involve any intervention, experimental or otherwise. Such a study may be one in which nature is allowed to take its course, with changes in one characteristic being studied in relation to changes in other characteristics. Analytical epidemiologic methods, such as case-control and cohort study designs, are properly called observational epidemiology because the investigator is observing without intervention other than to record, classify, count, and statistically analyze results. [NIH] Occipital Lobe: Posterior part of the cerebral hemisphere. [NIH] Occult: Obscure; concealed from observation, difficult to understand. [EU] Octreotide: A potent, long-acting somatostatin octapeptide analog which has a wide range of physiological actions. It inhibits growth hormone secretion, is effective in the treatment of hormone-secreting tumors from various organs, and has beneficial effects in the management of many pathological states including diabetes mellitus, orthostatic hypertension, hyperinsulinism, hypergastrinemia, and small bowel fistula. [NIH] Oculomotor: Cranial nerve III. It originate from the lower ventral surface of the midbrain and is classified as a motor nerve. [NIH] Office Visits: Visits made by patients to health service providers' offices for diagnosis, treatment, and follow-up. [NIH] Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or allow the uncontrolled growth of cancer. Alterations can be inherited or caused by an environmental exposure to carcinogens. [NIH] Oncology: The study of cancer. [NIH] On-line: A sexually-reproducing population derived from a common parentage. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Opium: The air-dried exudate from the unripe seed capsule of the opium poppy, Papaver somniferum, or its variant, P. album. It contains a number of alkaloids, but only a few morphine, codeine, and papaverine - have clinical significance. Opium has been used as an analgesic, antitussive, antidiarrheal, and antispasmodic. [NIH] Optic Chiasm: The X-shaped structure formed by the meeting of the two optic nerves. At the optic chiasm the fibers from the medial part of each retina cross to project to the other

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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 cup: The white, cup-like area in the center of the optic disc. [NIH] Optic Disk: The portion of the optic nerve seen in the fundus with the ophthalmoscope. It is formed by the meeting of all the retinal ganglion cell axons as they enter the optic nerve. [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] Oral Health: The optimal state of the mouth and normal functioning of the organs of the mouth without evidence of disease. [NIH] Orbit: One of the two cavities in the skull which contains an eyeball. Each eye is located in a bony socket or orbit. [NIH] Orbital: Pertaining to the orbit (= the bony cavity that contains the eyeball). [EU] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Oropharynx: Oral part of the pharynx. [NIH] Orthostatic: Pertaining to or caused by standing erect. [EU] Ossicles: The hammer, anvil and stirrup, the small bones of the middle ear, which transmit the vibrations from the tympanic membrane to the oval window. [NIH] Ossification: The formation of bone or of a bony substance; the conversion of fibrous tissue or of cartilage into bone or a bony substance. [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] Osteogenesis: The histogenesis of bone including ossification. It occurs continuously but particularly in the embryo and child and during fracture repair. [NIH] Osteogenesis Imperfecta: A collagen disorder resulting from defective biosynthesis of type I collagen and characterized by brittle, osteoporotic, and easily fractured bones. It may also present with blue sclerae, loose joints, and imperfect dentin formation. There are four major types, I-IV. [NIH] Osteotomy: The surgical cutting of a bone. [EU] Otitis: Inflammation of the ear, which may be marked by pain, fever, abnormalities of hearing, hearing loss, tinnitus, and vertigo. [EU] Otitis Media: Inflammation of the middle ear. [NIH] Otolaryngology: A surgical specialty concerned with the study and treatment of disorders of the ear, nose, and throat. [NIH] Otosclerosis: The formation of spongy bone in the labyrinth capsule. The ossicles can become fixed and unable to transmit sound vibrations, thereby causing deafness. [NIH] Outer ear: The pinna and external meatus of the ear. [NIH]

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Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Ovaries: The pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Overweight: An excess of body weight but not necessarily body fat; a body mass index of 25 to 29.9 kg/m2. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). [NIH] Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Oximetry: The determination of oxygen-hemoglobin saturation of blood either by withdrawing a sample and passing it through a classical photoelectric oximeter or by electrodes attached to some translucent part of the body like finger, earlobe, or skin fold. It includes non-invasive oxygen monitoring by pulse oximetry. [NIH] Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Oxygenation: The process of supplying, treating, or mixing with oxygen. No:1245 oxygenation the process of supplying, treating, or mixing with oxygen. [EU] Pacemaker: An object or substance that influences the rate at which a certain phenomenon occurs; often used alone to indicate the natural cardiac pacemaker or an artificial cardiac pacemaker. In biochemistry, a substance whose rate of reaction sets the pace for a series of interrelated reactions. [EU] Palate: The structure that forms the roof of the mouth. It consists of the anterior hard palate and the posterior soft palate. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Palsy: Disease of the peripheral nervous system occurring usually after many years of increased lead absorption. [NIH] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH]

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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] Paralysis: Loss of ability to move all or part of the body. [NIH] Paranasal Sinuses: Air-filled extensions of the respiratory part of the nasal cavity into the frontal, ethmoid, sphenoid, and maxillary cranial bones. They vary in size and form in different individuals and are lined by the ciliated mucous membranes of the nasal cavity. [NIH]

Parietal: 1. Of or pertaining to the walls of a cavity. 2. Pertaining to or located near the parietal bone, as the parietal lobe. [EU] Parietal Lobe: Upper central part of the cerebral hemisphere. [NIH] Parotid: The space that contains the parotid gland, the facial nerve, the external carotid artery, and the retromandibular vein. [NIH] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Particle: A tiny mass of material. [EU] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] 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 Advocacy: Promotion and protection of the rights of patients, frequently through a legal process. [NIH] Patient Compliance: Voluntary cooperation of the patient in following a prescribed regimen. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]

Patient Selection: Criteria and standards used for the determination of the appropriateness of the inclusion of patients with specific conditions in proposed treatment plans and the criteria used for the inclusion of subjects in various clinical trials and other research protocols. [NIH] Pedicle: Embryonic link between the optic vesicle or optic cup and the forebrain or diencephalon, which becomes the optic nerve. [NIH] Pelvic: Pertaining to the pelvis. [EU] Pemphigus: Group of chronic blistering diseases characterized histologically by acantholysis and blister formation within the epidermis. [NIH] Penicillin: An antibiotic drug used to treat infection. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Perception: The ability quickly and accurately to recognize similarities and differences

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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] Percutaneous: Performed through the skin, as injection of radiopacque material in radiological examination, or the removal of tissue for biopsy accomplished by a needle. [EU] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Periaqueductal Gray: Central gray matter surrounding the cerebral aqueduct in the mesencephalon. Physiologically it is probably involved in rage reactions, the lordosis reflex, feeding responses, bladder tonus, and pain. [NIH] Perilymph: The fluid contained within the space separating the membranous from the osseous labyrinth of the ear. [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] Periodontitis: Inflammation of the periodontal membrane; also called periodontitis simplex. [NIH]

Perioperative: Around the time of surgery; usually lasts from the time of going into the hospital or doctor's office for surgery until the time the patient goes home. [NIH] Peripheral 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 Vascular Disease: Disease in the large blood vessels of the arms, legs, and feet. People who have had diabetes for a long time may get this because major blood vessels in their arms, legs, and feet are blocked and these limbs do not receive enough blood. The signs of PVD are aching pains in the arms, legs, and feet (especially when walking) and foot sores that heal slowly. Although people with diabetes cannot always avoid PVD, doctors say they have a better chance of avoiding it if they take good care of their feet, do not smoke, and keep both their blood pressure and diabetes under good control. [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of Winslow, or epiploic foramen. [NIH] Peritoneal Dialysis: Dialysis fluid being introduced into and removed from the peritoneal cavity as either a continuous or an intermittent procedure. [NIH] Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering the inside of the abdominal wall and the visceral peritoneum covering the bowel, the

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mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal layer of the bowel wall. [NIH] Pertussis: An acute, highly contagious infection of the respiratory tract, most frequently affecting young children, usually caused by Bordetella pertussis; a similar illness has been associated with infection by B. parapertussis and B. bronchiseptica. It is characterized by a catarrhal stage, beginning after an incubation period of about two weeks, with slight fever, sneezing, running at the nose, and a dry cough. In a week or two the paroxysmal stage begins, with the characteristic paroxysmal cough, consisting of a deep inspiration, followed by a series of quick, short coughs, continuing until the air is expelled from the lungs; the close of the paroxysm is marked by a long-drawn, shrill, whooping inspiration, due to spasmodic closure of the glottis. This stage lasts three to four weeks, after which the convalescent stage begins, in which paroxysms grow less frequent and less violent, and finally cease. Called also whooping cough. [EU] Pharmaceutical Solutions: Homogeneous liquid preparations that contain one or more chemical substances dissolved, i.e., molecularly dispersed, in a suitable solvent or mixture of mutually miscible solvents. For reasons of their ingredients, method of preparation, or use, they do not fall into another group of products. [NIH] 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] Pharyngeal Muscles: The muscles of the pharynx are the inferior, middle and superior constrictors, salpingopharyngeus, and stylopharyngeus. [NIH] Pharyngitis: Inflammation of the throat. [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] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phonation: The process of producing vocal sounds by means of vocal cords vibrating in an expiratory blast of air. [NIH] Phonophoresis: Use of ultrasound to increase the percutaneous adsorption of drugs. [NIH] Phosphodiesterase: Effector enzyme that regulates the levels of a second messenger, the cyclic GMP. [NIH] Phosphodiesterase Inhibitors: Compounds which inhibit or antagonize the biosynthesis or actions of phosphodiesterases. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and

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teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylase: An enzyme of the transferase class that catalyzes the phosphorylysis of a terminal alpha-1,4-glycosidic bond at the non-reducing end of a glycogen molecule, releasing a glucose 1-phosphate residue. Phosphorylase should be qualified by the natural substance acted upon. EC 2.4.1.1. [NIH] Photocoagulation: Using a special strong beam of light (laser) to seal off bleeding blood vessels such as in the eye. The laser can also burn away blood vessels that should not have grown in the eye. This is the main treatment for diabetic retinopathy. [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. [NIH]

Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [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] Pickwickian Syndrome: Extreme obesity with polycythemia, somnolence, hypoventilation, arterial unsaturation and hypercapnia, and pulmonary hypertension. [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] Pitch: The subjective awareness of the frequency or spectral distribution of a sound. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] 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 cells: A type of white blood cell that produces antibodies. [NIH] Plasma Volume: Volume of plasma in the circulation. It is usually measured by indicator dilution techniques. [NIH] Plasticity: In an individual or a population, the capacity for adaptation: a) through gene changes (genetic plasticity) or b) through internal physiological modifications in response to changes of environment (physiological plasticity). [NIH]

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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]

Plethysmograph: An instrument for measuring swelling or expansion of the body or part of it, such as a limb or digit, commonly used for the indirect measurement of blood flow or other displacement of internal fluids. [NIH] Plethysmography: Recording of change in the size of a part as modified by the circulation in it. [NIH] Pleura: The thin serous membrane enveloping the lungs and lining the thoracic cavity. [NIH] Pleural: A circumscribed area of hyaline whorled fibrous tissue which appears on the surface of the parietal pleura, on the fibrous part of the diaphragm or on the pleura in the interlobar fissures. [NIH] Pleural cavity: A space enclosed by the pleura (thin tissue covering the lungs and lining the interior wall of the chest cavity). It is bound by thin membranes. [NIH] Pleural Effusion: Presence of fluid in the pleural cavity resulting from excessive transudation or exudation from the pleural surfaces. It is a sign of disease and not a diagnosis in itself. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polycystic: An inherited disorder characterized by many grape-like clusters of fluid-filled cysts that make both kidneys larger over time. These cysts take over and destroy working kidney tissue. PKD may cause chronic renal failure and end-stage renal disease. [NIH] Polymers: Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., polypeptides, proteins, plastics). [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] 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] Polyuria: Urination of a large volume of urine with an increase in urinary frequency, commonly seen in diabetes. [NIH] Pons: The part of the central nervous system lying between the medulla oblongata and the mesencephalon, ventral to the cerebellum, and consisting of a pars dorsalis and a pars ventralis. [NIH] Pontine: A brain region involved in the detection and processing of taste. [NIH]

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Port: An implanted device through which blood may be withdrawn and drugs may be infused without repeated needle sticks. Also called a port-a-cath. [NIH] Port-a-cath: An implanted device through which blood may be withdrawn and drugs may be infused without repeated needle sticks. Also called a port. [NIH] Positive pressure ventilation: Provision of oxygen under pressure by a mechanical respirator. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postoperative: After surgery. [NIH] Postoperative Complications: Pathologic processes that affect patients after a surgical procedure. They may or may not be related to the disease for which the surgery was done, and they may or may not be direct results of the surgery. [NIH] Postprandial: Occurring after dinner, or after a meal; postcibal. [EU] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potentiate: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] 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 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] 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] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Prefrontal Cortex: The rostral part of the frontal lobe, bounded by the inferior precentral fissure in humans, which receives projection fibers from the mediodorsal nucleus of the thalamus. The prefrontal cortex receives afferent fibers from numerous structures of the diencephalon, mesencephalon, and limbic system as well as cortical afferents of visual, auditory, and somatic origin. [NIH] Premenstrual: Occurring before menstruation. [EU]

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Premenstrual Syndrome: A syndrome occurring most often during the last week of the menstrual cycle and ending soon after the onset of menses. Some of the symptoms are emotional instability, insomnia, headache, nausea, vomiting, abdominal distension, and painful breasts. [NIH] Preoptic Area: Region of hypothalamus between the anterior commissure and optic chiasm. [NIH]

Pressoreceptors: Receptors in the vascular system, particularly the aorta and carotid sinus, which are sensitive to stretch of the vessel walls. [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] Primary endpoint: The main result that is measured at the end of a study to see if a given treatment worked (e.g., the number of deaths or the difference in survival between the treatment group and the control group). What the primary endpoint will be is decided before the study begins. [NIH] Primary Prevention: Prevention of disease or mental disorders in susceptible individuals or populations through promotion of health, including mental health, and specific protection, as in immunization, as distinguished from the prevention of complications or after-effects of existing disease. [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] Progeny: The offspring produced in any generation. [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] 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] Prone: Having the front portion of the body downwards. [NIH] Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] 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]

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Prospective Studies: Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond (5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane). The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also). The effect produced by the cyclic AMP increase depends on the specific cell type. In some cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] 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] Prosthodontics: A dental specialty concerned with the restoration and maintenance of oral function by the replacement of missing teeth and structures by artificial devices or prostheses. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Pseudotumor Cerebri: A condition marked by raised intracranial pressure and characterized clinically by headaches; nausea; papilledema, peripheral constriction of the visual fields, transient visual obscurations, and pulsatile tinnitus. Obesity is frequently

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associated with this condition, which primarily affects women between 20 and 44 years of age. Chronic papilledema may lead to optic nerve injury (optic nerve diseases) and visual loss (blindness). [NIH] Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] 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] 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] Puberty: The period during which the secondary sex characteristics begin to develop and the capability of sexual reproduction is attained. [EU] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] 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 Alveoli: Small polyhedral outpouchings along the walls of the alveolar sacs, alveolar ducts and terminal bronchioles through the walls of which gas exchange between alveolar air and pulmonary capillary blood takes place. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary Circulation: The circulation of blood through the lungs. [NIH] Pulmonary Edema: An accumulation of an excessive amount of watery fluid in the lungs, may be caused by acute exposure to dangerous concentrations of irritant gasses. [NIH] Pulmonary hypertension: Abnormally high blood pressure in the arteries of the lungs. [NIH] Pulmonary Ventilation: The total volume of gas per minute inspired or expired measured in liters per minute. [NIH] Pulsation: A throb or rhythmical beat, as of the heart. [EU] Pulse: The rhythmical expansion and contraction of an artery produced by waves of

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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] Purulent: Consisting of or containing pus; associated with the formation of or caused by pus. [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] 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] Radiography: Examination of any part of the body for diagnostic purposes by means of roentgen rays, recording the image on a sensitized surface (such as photographic film). [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [NIH] Radiopharmaceutical: Any medicinal product which, when ready for use, contains one or more radionuclides (radioactive isotopes) included for a medicinal purpose. [NIH] Rage: Fury; violent, intense anger. [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] Randomized Controlled Trials: Clinical trials that involve at least one test treatment and one control treatment, concurrent enrollment and follow-up of the test- and control-treated groups, and in which the treatments to be administered are selected by a random process, such as the use of a random-numbers table. Treatment allocations using coin flips, odd-even numbers, patient social security numbers, days of the week, medical record numbers, or other such pseudo- or quasi-random processes, are not truly randomized and trials employing any of these techniques for patient assignment are designated simply controlled clinical trials. [NIH] Raphe Nuclei: Collections of small neurons centrally scattered among many fibers from the level of the trochlear nucleus in the midbrain to the hypoglossal area in the medulla

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oblongata. [NIH] Reactive Oxygen Species: Reactive intermediate oxygen species including both radicals and non-radicals. These substances are constantly formed in the human body and have been shown to kill bacteria and inactivate proteins, and have been implicated in a number of diseases. Scientific data exist that link the reactive oxygen species produced by inflammatory phagocytes to cancer development. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Receptors, Serotonin: Cell-surface proteins that bind serotonin and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] 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] Recurrent Laryngeal Nerve: Branches of the vagus (tenth cranial) nerve. The recurrent laryngeal nerves originate more caudally than the superior laryngeal nerves and follow different paths on the right and left sides. They carry efferents to all muscles of the larynx except the cricothyroid and carry sensory and autonomic fibers to the laryngeal, pharyngeal, tracheal, and cardiac regions. [NIH] Red Nucleus: A pinkish-yellow portion of the midbrain situated in the rostral mesencephalic tegmentum. It receives a large projection from the contralateral half of the cerebellum via the superior cerebellar peduncle and a projection from the ipsilateral motor cortex. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflex: An involuntary movement or exercise of function in a part, excited in response to a stimulus applied to the periphery and transmitted to the brain or spinal cord. [NIH] Reflux: The term used when liquid backs up into the esophagus from the stomach. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Refractory: Not readily yielding to treatment. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] 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] Relaxant: 1. Lessening or reducing tension. 2. An agent that lessens tension. [EU] Reliability: Used technically, in a statistical sense, of consistency of a test with itself, i. e. the extent to which we can assume that it will yield the same result if repeated a second time.

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[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] Renin: An enzyme which is secreted by the kidney and is formed from prorenin in plasma and kidney. The enzyme cleaves the Leu-Leu bond in angiotensinogen to generate angiotensin I. EC 3.4.23.15. (Formerly EC 3.4.99.19). [NIH] Renin-Angiotensin System: A system consisting of renin, angiotensin-converting enzyme, and angiotensin II. Renin, an enzyme produced in the kidney, acts on angiotensinogen, an alpha-2 globulin produced by the liver, forming angiotensin I. The converting enzyme contained in the lung acts on angiotensin I in the plasma converting it to angiotensin II, the most powerful directly pressor substance known. It causes contraction of the arteriolar smooth muscle and has other indirect actions mediated through the adrenal cortex. [NIH] Reperfusion: Restoration of blood supply to tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. It is primarily a procedure for treating infarction or other ischemia, by enabling viable ischemic tissue to recover, thus limiting further necrosis. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing reperfusion injury. [NIH] Reperfusion Injury: Functional, metabolic, or structural changes, including necrosis, in ischemic tissues thought to result from reperfusion to ischemic areas of the tissue. The most common instance is myocardial reperfusion injury. [NIH] Research Support: Financial support of research activities. [NIH] Residual Volume: The volume of air remaining in the lungs at the end of a maximal expiration. Common abbreviation is RV. [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] Respiration Disorders: Diseases of the respiratory system in general or unspecified or for a specific respiratory disease not available. [NIH] Respirator: A mechanical device that helps a patient breathe; a mechanical ventilator. [NIH] Respiratory distress syndrome: A lung disease that occurs primarily in premature infants; the newborn must struggle for each breath and blueing of its skin reflects the baby's inability to get enough oxygen. [NIH] Respiratory failure: Inability of the lungs to conduct gas exchange. [NIH] Respiratory Muscles: These include the muscles of the diaphragm and the intercostal muscles. [NIH] Respiratory Physiology: Functions and activities of the respiratory tract as a whole or of any of its parts. [NIH] Respiratory System: The tubular and cavernous organs and structures, by means of which pulmonary ventilation and gas exchange between ambient air and the blood are brought about. [NIH]

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Response rate: The percentage of patients whose cancer shrinks or disappears after treatment. [NIH] Restless legs: Legs characterized by or showing inability to remain at rest. [EU] 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] Retractor: An instrument designed for pulling aside tissues to improve exposure at operation; an instrument for drawing back the edge of a wound. [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] 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] Rhinitis: Inflammation of the mucous membrane of the nose. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Risk patient: Patient who is at risk, because of his/her behaviour or because of the type of person he/she is. [EU] Rod: A reception for vision, located in the retina. [NIH] Sagittal: The line of direction passing through the body from back to front, or any vertical plane parallel to the medial plane of the body and inclusive of that plane; often restricted to the medial plane, the plane of the sagittal suture. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the

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mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Salivation: 1. The secretion of saliva. 2. Ptyalism (= excessive flow of saliva). [EU] Saphenous: Applied to certain structures in the leg, e. g. nerve vein. [NIH] Saphenous Vein: The vein which drains the foot and leg. [NIH] Saponins: Sapogenin glycosides. A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycon moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics when injected into the blood stream able to dissolve red blood cells at even extreme dilutions. [NIH] Sarcoidosis: An idiopathic systemic inflammatory granulomatous disorder comprised of epithelioid and multinucleated giant cells with little necrosis. It usually invades the lungs with fibrosis and may also involve lymph nodes, skin, liver, spleen, eyes, phalangeal bones, and parotid glands. [NIH] Scans: Pictures of structures inside the body. Scans often used in diagnosing, staging, and monitoring disease include liver scans, bone scans, and computed tomography (CT) or computerized axial tomography (CAT) scans and magnetic resonance imaging (MRI) scans. In liver scanning and bone scanning, radioactive substances that are injected into the bloodstream collect in these organs. A scanner that detects the radiation is used to create pictures. In CT scanning, an x-ray machine linked to a computer is used to produce detailed pictures of organs inside the body. MRI scans use a large magnet connected to a computer to create pictures of areas inside the body. [NIH] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] Sclerae: A circular furrow between the sclerocorneal junction and the iris. [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] 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] Secondary tumor: Cancer that has spread from the organ in which it first appeared to another organ. For example, breast cancer cells may spread (metastasize) to the lungs and cause the growth of a new tumor. When this happens, the disease is called metastatic breast

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cancer, and the tumor in the lungs is called a secondary tumor. Also called secondary cancer. [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] Segmental: Describing or pertaining to a structure which is repeated in similar form in successive segments of an organism, or which is undergoing segmentation. [NIH] Segmentation: The process by which muscles in the intestines move food and wastes through the body. [NIH] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [NIH] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Selection Bias: The introduction of error due to systematic differences in the characteristics between those selected and those not selected for a given study. In sampling bias, error is the result of failure to ensure that all members of the reference population have a known chance of selection in the sample. [NIH] Self-Help Groups: Organizations which provide an environment encouraging social interactions through group activities or individual relationships especially for the purpose of rehabilitating or supporting patients, individuals with common health problems, or the elderly. They include therapeutic social clubs. [NIH] Sella: A deep depression in the shape of a Turkish saddle in the upper surface of the body of the sphenoid bone in the deepest part of which is lodged the hypophysis cerebri. [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Sensibility: The ability to receive, feel and appreciate sensations and impressions; the quality of being sensitive; the extend to which a method gives results that are free from false negatives. [NIH] Sensitization: 1. Administration of antigen to induce a primary immune response; priming; immunization. 2. Exposure to allergen that results in the development of hypersensitivity. 3. The coating of erythrocytes with antibody so that they are subject to lysis by complement in the presence of homologous antigen, the first stage of a complement fixation test. [EU] Sensor: A device designed to respond to physical stimuli such as temperature, light, magnetism or movement and transmit resulting impulses for interpretation, recording, movement, or operating control. [NIH] Sensory Deprivation: The absence or restriction of the usual external sensory stimuli to which the individual responds. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important

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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] Serous: Having to do with serum, the clear liquid part of blood. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Sex Determination: The biological characteristics which distinguish human beings as female or male. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]

Shunt: A surgically created diversion of fluid (e.g., blood or cerebrospinal fluid) from one area of the body to another area of the body. [NIH] Sibutramine: A drug used for the management of obesity that helps reduce food intake and is indicated for weight loss and maintenance of weight loss when used in conjunction with a reduced-calorie diet. It works to suppress the appetite primarily by inhibiting the reuptake of the neurotransmitters norepinephrine and serotonin. Side effects include dry mouth, headache, constipation, insomnia, and a slight increase in average blood pressure. In some patients it causes a higher blood pressure increase. [NIH] Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Sinusitis: An inflammatory process of the mucous membranes of the paranasal sinuses that occurs in three stages: acute, subacute, and chronic. Sinusitis results from any condition causing ostial obstruction or from pathophysiologic changes in the mucociliary transport mechanism. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects

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many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Sleep apnea: A serious, potentially life-threatening breathing disorder characterized by repeated cessation of breathing due to either collapse of the upper airway during sleep or absence of respiratory effort. [NIH] Sleep Apnea Syndromes: Disorders characterized by multiple cessations of respirations during sleep that induce partial arousals and interfere with the maintenance of sleep. Sleep apnea syndromes are divided into central (sleep apena, central), obstructive (sleep apnea, obstructive), and mixed central-obstructive types. [NIH] Sleep Deprivation: The state of being deprived of sleep under experimental conditions, due to life events, or from a wide variety of pathophysiologic causes such as medication effect, chronic illness, psychiatric illness, or sleep disorder. [NIH] Sleep Stages: Periods of sleep manifested by changes in EEG activity and certain behavioral correlates; includes Stage 1: sleep onset, drowsy sleep; Stage 2: light sleep; Stages 3 and 4: delta sleep, light sleep, deep sleep, telencephalic sleep. [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] 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 Cyanide: Na(CN). A highly poisonous compound that is an inhibitor of many metabolic processes and is used as a test reagent for the function of chemoreceptors. It is also used in many industrial processes. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Solitary Nucleus: Gray matter located in the dorsomedial part of the medulla oblongata associated with the solitary tract. The solitary nucleus receives inputs from most organ systems including the terminations of the facial, glossopharyngeal, and vagus nerves. It is a major coordinator of autonomic nervous system regulation of cardiovascular, respiratory, gustatory, gastrointestinal, and chemoreceptive aspects of homeostasis. The solitary nucleus is also notable for the large number of neurotransmitters which are found therein. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall

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in contrast to the viscera. [EU] Somatostatin: A polypeptide hormone produced in the hypothalamus, and other tissues and organs. It inhibits the release of human growth hormone, and also modulates important physiological functions of the kidney, pancreas, and gastrointestinal tract. Somatostatin receptors are widely expressed throughout the body. Somatostatin also acts as a neurotransmitter in the central and peripheral nervous systems. [NIH] Somnolence: Sleepiness; also unnatural drowsiness. [EU] Sound wave: An alteration of properties of an elastic medium, such as pressure, particle displacement, or density, that propagates through the medium, or a superposition of such alterations. [NIH] Spasm: An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. [NIH] Spasmodic: Of the nature of a spasm. [EU] Spastic: 1. Of the nature of or characterized by spasms. 2. Hypertonic, so that the muscles are stiff and the movements awkward. 3. A person exhibiting spasticity, such as occurs in spastic paralysis or in cerebral palsy. [EU] Spatial disorientation: Loss of orientation in space where person does not know which way is up. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrometer: An apparatus for determining spectra; measures quantities such as wavelengths and relative amplitudes of components. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] Spermatogenesis: Process of formation and development of spermatozoa, including spermatocytogenesis and spermiogenesis. [NIH] Spermatozoa: Mature male germ cells that develop in the seminiferous tubules of the testes. Each consists of a head, a body, and a tail that provides propulsion. The head consists mainly of chromatin. [NIH] Sphincter: A ringlike band of muscle fibres that constricts a passage or closes a natural orifice; called also musculus sphincter. [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] Spinal Nerves: The 31 paired peripheral nerves formed by the union of the dorsal and ventral spinal roots from each spinal cord segment. The spinal nerve plexuses and the spinal roots are also included. [NIH]

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Spirochete: Lyme disease. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Splenomegaly: Enlargement of the spleen. [NIH] Splint: A rigid appliance used for the immobilization of a part or for the correction of deformity. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Squamous: Scaly, or platelike. [EU] Squamous Epithelium: Tissue in an organ such as the esophagus. Consists of layers of flat, scaly cells. [NIH] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH]

Stapes: One of the three ossicles of the middle ear. It transmits sound vibrations from the incus to the internal ear. [NIH] Steatosis: Fatty degeneration. [EU] Steel: A tough, malleable, iron-based alloy containing up to, but no more than, two percent carbon and often other metals. It is used in medicine and dentistry in implants and instrumentation. [NIH] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]

Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] 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] Stroke Volume: The amount of blood pumped out of the heart per beat not to be confused with cardiac output (volume/time). [NIH] Stromal: Large, veil-like cell in the bone marrow. [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]

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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] Subiculum: A region of the hippocampus that projects to other areas of the brain. [NIH] Submandibular: Four to six lymph glands, located between the lower jaw and the submandibular salivary gland. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]

Substrate: A substance upon which an enzyme acts. [EU] Succinylcholine: A quaternary skeletal muscle relaxant usually used in the form of its bromide, chloride, or iodide. It is a depolarizing relaxant, acting in about 30 seconds and with a duration of effect averaging three to five minutes. Succinylcholine is used in surgical, anesthetic, and other procedures in which a brief period of muscle relaxation is called for. [NIH]

Suction: The removal of secretions, gas or fluid from hollow or tubular organs or cavities by means of a tube and a device that acts on negative pressure. [NIH] Sufentanil: An opioid analgesic that is used as an adjunct in anesthesia, in balanced anesthesia, and as a primary anesthetic agent. [NIH] Sumatriptan: A serotonin agonist that acts selectively at 5HT1 receptors. It is used in the treatment of migraines. [NIH] Superior Cervical Ganglion: The largest and uppermost of the paravertebral sympathetic ganglia. [NIH] Superoxide: Derivative of molecular oxygen that can damage cells. [NIH] Superoxide Dismutase: An oxidoreductase that catalyzes the reaction between superoxide anions and hydrogen to yield molecular oxygen and hydrogen peroxide. The enzyme protects the cell against dangerous levels of superoxide. EC 1.15.1.1. [NIH] Supine: Having the front portion of the body upwards. [NIH] Supine Position: The posture of an individual lying face up. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Support group: A group of people with similar disease who meet to discuss how better to cope with their cancer and treatment. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [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

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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] Synaptic Transmission: The communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. In chemical synaptic transmission, the presynaptic neuron releases a neurotransmitter that diffuses across the synaptic cleft and binds to specific synaptic receptors. These activated receptors modulate ion channels and/or secondmessenger systems to influence the postsynaptic cell. Electrical transmission is less common in the nervous system, and, as in other tissues, is mediated by gap junctions. [NIH] Synaptic Vesicles: Membrane-bound compartments which contain transmitter molecules. Synaptic vesicles are concentrated at presynaptic terminals. They actively sequester transmitter molecules from the cytoplasm. In at least some synapses, transmitter release occurs by fusion of these vesicles with the presynaptic membrane, followed by exocytosis of their contents. [NIH] Synchrony: The normal physiologic sequencing of atrial and ventricular activation and contraction. [NIH] Syncope: A temporary suspension of consciousness due to generalized cerebral schemia, a faint or swoon. [EU] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Syphilis: A contagious venereal disease caused by the spirochete Treponema pallidum. [NIH]

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] Telangiectasia: The permanent enlargement of blood vessels, causing redness in the skin or

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mucous membranes. [NIH] Telecommunications: Transmission of information over distances via electronic means. [NIH]

Telemedicine: Delivery of health services via remote telecommunications. This includes interactive consultative and diagnostic services. [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Temporal Lobe: Lower lateral part of the cerebral hemisphere. [NIH] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Thalamic: Cell that reaches the lateral nucleus of amygdala. [NIH] Thalamic Diseases: Disorders of the centrally located thalamus, which integrates a wide range of cortical and subcortical information. Manifestations include sensory loss, movement disorders; ataxia, pain syndromes, visual disorders, a variety of neuropsychological conditions, and coma. Relatively common etiologies include cerebrovascular disorders; craniocerebral trauma; brain neoplasms; brain hypoxia; intracranial hemorrhages; and infectious processes. [NIH] Thalamus: Paired bodies containing mostly gray substance and forming part of the lateral wall of the third ventricle of the brain. The thalamus represents the major portion of the diencephalon and is commonly divided into cellular aggregates known as nuclear groups. [NIH]

Theophylline: Alkaloid obtained from Thea sinensis (tea) and others. It stimulates the heart and central nervous system, dilates bronchi and blood vessels, and causes diuresis. The drug is used mainly in bronchial asthma and for myocardial stimulation. Among its more prominent cellular effects are inhibition of cyclic nucleotide phosphodiesterases and antagonism of adenosine receptors. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Thermoregulation: Heat regulation. [EU] Third Ventricle: A narrow cleft inferior to the corpus callosum, within the diencephalon, between the paired thalami. Its floor is formed by the hypothalamus, its anterior wall by the lamina terminalis, and its roof by ependyma. It communicates with the fourth ventricle by the cerebral aqueduct, and with the lateral ventricles by the interventricular foramina. [NIH] 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] Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU]

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Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Tidal Volume: The volume of air inspired or expired during each normal, quiet respiratory cycle. Common abbreviations are TV or V with subscript T. [NIH] 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] Tonometry: The standard to determine the fluid pressure inside the eye (intraocular pressure). [NIH] Tonsillitis: Inflammation of the tonsils, especially the palatine tonsils. It is often caused by a bacterium. Tonsillitis may be acute, chronic, or recurrent. [NIH] Tonsils: Small masses of lymphoid tissue on either side of the throat. [NIH] Tonus: A state of slight tension usually present in muscles even when they are not undergoing active contraction. [NIH] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] Torsion: A twisting or rotation of a bodily part or member on its axis. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] 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]

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Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Tracheostomy: Surgical formation of an opening into the trachea through the neck, or the opening so created. [NIH] Tracheotomy: Surgical incision of the trachea. [NIH] Traction: The act of pulling. [NIH] Tractus: A part of some structure, usually that part along which something passes. [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] Transcutaneous: Transdermal. [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] Transfer Factor: Factor derived from leukocyte lysates of immune donors which can transfer both local and systemic cellular immunity to nonimmune recipients. [NIH] Transfusion: The infusion of components of blood or whole blood into the bloodstream. The blood may be donated from another person, or it may have been taken from the person earlier and stored until needed. [NIH] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, practicability, etc., of these interventions in individual cases or series. [NIH]

Tremor: Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of cerebellar diseases, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of Parkinson disease. [NIH] Tricuspid Atresia: Absence of the orifice between the right atrium and ventricle, with the presence of an atrial defect through which all the systemic venous return reaches the left heart. As a result, there is left ventricular hypertrophy because the right ventricle is absent or not functional. [NIH]

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Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tubercle: A rounded elevation on a bone or other structure. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH] Tuberous Sclerosis: A rare congenital disease in which the essential pathology is the appearance of multiple tumors in the cerebrum and in other organs, such as the heart or kidneys. [NIH] Tubulin: A microtubule subunit protein found in large quantities in mammalian brain. It has also been isolated from sperm flagella, cilia, and other sources. Structurally, the protein is a dimer with a molecular weight of approximately 120,000 and a sedimentation coefficient of 5.8S. It binds to colchicine, vincristine, and vinblastine. [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] Tumour: 1. Swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. A new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU] Turbinates: The scroll-like bony plates with curved margins on the lateral wall of the nasal cavity. [NIH] Type 2 diabetes: Usually characterized by a gradual onset with minimal or no symptoms of metabolic disturbance and no requirement for exogenous insulin. The peak age of onset is 50 to 60 years. Obesity and possibly a genetic factor are usually present. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ultrafiltration: The separation of particles from a suspension by passage through a filter with very fine pores. In ultrafiltration the separation is accomplished by convective transport; in dialysis separation relies instead upon differential diffusion. Ultrafiltration occurs naturally and is a laboratory procedure. Artificial ultrafiltration of the blood is referred to as hemofiltration or hemodiafiltration (if combined with hemodialysis). [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Uremia: The illness associated with the buildup of urea in the blood because the kidneys are not working effectively. Symptoms include nausea, vomiting, loss of appetite, weakness, and mental confusion. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Uric: A kidney stone that may result from a diet high in animal protein. When the body breaks down this protein, uric acid levels rise and can form stones. [NIH] Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH]

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Urinate: To release urine from the bladder to the outside. [NIH] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] 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] Vagal: Pertaining to the vagus nerve. [EU] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] 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] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vascular endothelial growth factor: VEGF. A substance made by cells that stimulates new blood vessel formation. [NIH] 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] Vascular Resistance: An expression of the resistance offered by the systemic arterioles, and to a lesser extent by the capillaries, to the flow of blood. [NIH] Vasoactive: Exerting an effect upon the calibre of blood vessels. [EU] 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] Vasodilation: Physiological dilation of the blood vessels without anatomic change. For dilation with anatomic change, dilatation, pathologic or aneurysm (or specific aneurysm) is used. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] 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] Velopharyngeal Insufficiency: Failure of the soft palate to reach the posterior pharyngeal wall. It may be caused by cleft palate surgery, palatal or pharyngeal abnormalities or injury, or neuromuscular dysfunction of the velopharyngeal sphincter. It causes hypernasality of speech. [NIH] Venereal: Pertaining or related to or transmitted by sexual contact. [EU] 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

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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] Ventricular: Pertaining to a ventricle. [EU] Ventricular Dysfunction: A condition in which the ventricles of the heart exhibit a decreased functionality. [NIH] Ventricular Function: The hemodynamic and electrophysiological action of the ventricles. [NIH]

Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vertebrae: A bony unit of the segmented spinal column. [NIH] Vertigo: An illusion of movement; a sensation as if the external world were revolving around the patient (objective vertigo) or as if he himself were revolving in space (subjective vertigo). The term is sometimes erroneously used to mean any form of dizziness. [EU] Vestibular: Pertaining to or toward a vestibule. In dental anatomy, used to refer to the tooth surface directed toward the vestibule of the mouth. [EU] Vestibule: A small, oval, bony chamber of the labyrinth. The vestibule contains the utricle and saccule, organs which are part of the balancing apparatus of the ear. [NIH] Vestibulocochlear Nerve: The 8th cranial nerve. The vestibulocochlear nerve has a cochlear part (cochlear nerve) which is concerned with hearing and a vestibular part (vestibular nerve) which mediates the sense of balance and head position. The fibers of the cochlear nerve originate from neurons of the spiral ganglion and project to the cochlear nuclei (cochlear nucleus). The fibers of the vestibular nerve arise from neurons of Scarpa's ganglion and project to the vestibular nuclei. [NIH] Vestibulocochlear Nerve Diseases: Diseases of the vestibular and/or cochlear (acoustic) nerves, which join to form the vestibulocochlear nerve. Vestibular neuritis, cochlear neuritis, and acoustic neuromas are relatively common conditions that affect these nerves. Clinical manifestations vary with which nerve is primarily affected, and include hearing loss, vertigo, and tinnitus. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Virilism: Development of masculine traits in the female. [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

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kill, tumor cells. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Visceral Afferents: The sensory fibers innervating the viscera. [NIH] Viscosity: A physical property of fluids that determines the internal resistance to shear forces. [EU] Vitamin A: A substance used in cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Vitreous Hemorrhage: Hemorrhage into the vitreous body. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Vocal cord: The vocal folds of the larynx. [NIH] Voice Disorders: Disorders of voice pitch, loudness, or quality. Dysphonia refers to impaired utterance of sounds by the vocal folds. [NIH] Wakefulness: A state in which there is an enhanced potential for sensitivity and an efficient responsiveness to external stimuli. [NIH] Weight Gain: Increase in body weight over existing weight. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]

Whooping Cough: A respiratory infection caused by Bordetella pertussis and characterized by paroxysmal coughing ending in a prolonged crowing intake of breath. [NIH] Whooping Cough: A respiratory infection caused by Bordetella pertussis and characterized by paroxysmal coughing ending in a prolonged crowing intake of breath. [NIH] Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Womb: A hollow, thick-walled, muscular organ in which the impregnated ovum is developed into a child. [NIH] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] Xerostomia: Decreased salivary flow. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Yohimbine: A plant alkaloid with alpha-2-adrenergic blocking activity. Yohimbine has been used as a mydriatic and in the treatment of impotence. It is also alleged to be an aphrodisiac. [NIH]

333

INDEX A Abdomen, 144, 251, 259, 260, 265, 293, 305, 306, 323, 326, 330 Abdominal, 63, 145, 164, 165, 189, 251, 252, 272, 291, 296, 304, 306, 311 Abdominal fat, 63, 251 Abdominal Pain, 251, 291 Ablation, 57, 105, 251 Abscess, 202, 205, 251 Acantholysis, 251, 305 Acceptor, 251, 293, 304 Acetylcholine, 23, 251, 265, 301 Acidosis, 26, 74, 251 Acoustic, 14, 51, 143, 155, 172, 251, 289, 331 Actin, 251, 299 Adaptability, 251, 263, 264 Adaptation, 36, 251, 308 Adduction, 205, 251 Adenine, 162, 251 Adenosine, 33, 110, 162, 251, 261, 308, 326 Adipocytes, 252, 292 Adipose Tissue, 175, 251, 252 Adjustment, 140, 166, 251, 252 Adjuvant, 189, 252 Adolescence, 132, 252 Adrenal Cortex, 252, 253, 270, 285, 311, 316 Adrenal Medulla, 58, 252, 263, 277, 301 Adrenergic, 16, 29, 35, 67, 169, 252, 255, 274, 277, 325, 332 Adverse Effect, 32, 212, 252, 320 Aerobic, 252, 297 Afferent, 55, 252, 278, 292, 310 Affinity, 29, 252, 257, 300, 321 Age Groups, 61, 252 Age of Onset, 252, 329 Aged, 80 and Over, 252 Agonist, 29, 40, 52, 162, 188, 252, 262, 274, 301, 324 Airway Resistance, 7, 38, 110, 138, 140, 166, 253 Aldosterone, 151, 253 Alertness, 45, 131, 138, 164, 253, 261 Alexia, 253, 274 Algorithms, 253, 259 Alkaline, 251, 253, 261 Alkaloid, 253, 266, 297, 301, 326, 332

Allergen, 253, 319 Alternative medicine, 213, 253 Alveoli, 253, 272, 331 Ameliorating, 139, 253 Amino Acid Sequence, 253, 255, 280 Amino Acids, 141, 253, 280, 305, 309, 312, 317, 328 Amphetamines, 253, 266 Ampulla, 253, 276 Amygdala, 44, 253, 258, 292, 326 Amyloid, 107, 253 Anaesthesia, 114, 117, 254, 288 Anaesthetic, 111, 190, 254 Anal, 254, 279, 293 Analgesic, 65, 188, 254, 268, 297, 302, 324 Analog, 61, 254, 292, 302 Analogous, 164, 186, 254, 328 Anaphylatoxins, 254, 267 Anaplasia, 254 Anastomosis, 205, 254 Anatomical, 14, 15, 16, 25, 53, 62, 138, 199, 203, 254, 257, 265, 268, 273, 287, 300, 318 Androgens, 17, 252, 254, 285 Anemia, 4, 230, 254, 283 Anemic, 73, 254 Anesthesia, 79, 89, 114, 117, 158, 202, 205, 252, 254, 255, 268, 275, 315, 324 Anesthetics, 158, 254, 258, 264, 277 Aneurism, 183, 254 Aneurysm, 254, 330 Angina, 205, 254 Angiogenesis, 38, 254 Angiography, 4, 254 Angioplasty, 4, 254 Angiotensin-Converting Enzyme Inhibitors, 198, 255 Animal model, 4, 29, 40, 45, 52, 66, 121, 255 Anions, 255, 290, 324 Anomalies, 203, 208, 255 Antagonism, 114, 255, 261, 326 Anterograde, 16, 255 Anthropometric measurements, 62, 255 Anthropometry, 35, 255 Anti-Anxiety Agents, 255, 313, 328 Antibacterial, 255, 322 Antibiotic, 255, 305, 322 Antibodies, 141, 255, 282, 285, 287, 308

334 Apnea

Antibody, 252, 255, 256, 267, 282, 284, 286, 287, 288, 295, 314, 319, 322 Anticonvulsant, 255, 266 Antidepressant, 169, 255, 261 Antidepressive Agents, 255, 313 Antiepileptic, 32, 256 Antigen, 252, 255, 256, 267, 281, 284, 286, 287, 288, 295, 319 Antigen-Antibody Complex, 256, 267 Antihypertensive, 162, 256 Antioxidant, 256, 304 Anxiety, 170, 255, 256, 268, 286 Aorta, 151, 256, 269, 311, 331 Apathy, 153, 184, 256 Apnoea, 176, 256 Aponeurosis, 256, 280 Apoptosis, 39, 256 Applicability, 146, 173, 256 Approximate, 137, 256 Aqueous, 256, 258, 271, 285 Arachidonic Acid, 256, 312 Arginine, 188, 254, 256, 301 Arrhythmia, 56, 138, 146, 159, 173, 234, 256 Arterial, 13, 20, 30, 51, 54, 58, 67, 70, 72, 80, 102, 144, 148, 151, 158, 167, 173, 256, 257, 269, 285, 286, 308, 312, 325 Arteries, 51, 165, 256, 260, 264, 269, 270, 291, 294, 296, 298, 313 Arterioles, 43, 256, 260, 296, 298, 330 Arteriovenous, 257, 296 Articular, 257, 303 Artifacts, 46, 148, 257 Aspiration, 203, 257 Astrocytes, 72, 257, 281, 297, 300 Ataxia, 229, 257, 285, 326 Atmospheric Pressure, 139, 144, 174, 257 Atrial, 29, 72, 100, 151, 212, 257, 269, 325, 328 Atrial Fibrillation, 29, 100, 257 Atrioventricular, 257, 269 Atrium, 257, 269, 328, 331 Atrophy, 229, 251, 257 Attenuated, 20, 26, 29, 57, 67, 257 Attenuation, 16, 20, 257 Atypical, 257, 288 Auditory, 122, 203, 257, 275, 277, 282, 285, 295, 310, 330 Autoimmune disease, 257, 298 Autologous, 205, 257 Autonomic, 16, 37, 44, 81, 96, 106, 115, 151, 251, 257, 292, 301, 306, 315, 321, 324

Autonomic Nervous System, 151, 257, 306, 321, 324 Autosuggestion, 258, 287 Axonal, 16, 258 Axons, 16, 258, 272, 303, 306, 311 B Bacteria, 255, 256, 258, 275, 276, 277, 292, 296, 297, 315, 322, 328, 330 Bacterial Physiology, 251, 258 Bacteriophage, 258, 308, 328 Bacterium, 258, 327 Barbiturate, 115, 258 Baroreflex, 16, 41, 51, 258 Basal Ganglia, 257, 258, 280, 293 Basal Ganglia Diseases, 257, 258 Base, 9, 97, 107, 142, 143, 160, 165, 176, 178, 251, 258, 272, 277, 280, 291, 326 Benign, 141, 199, 258, 280, 282, 293, 300 Benign tumor, 258, 293 Benzene, 258, 259 Benzodiazepines, 202, 259 Beta blocker, 198, 259 Beta-pleated, 253, 259 Bilateral, 73, 100, 259 Bile, 259, 279, 280, 291, 293, 323 Bile Acids, 259, 280, 323 Bile Pigments, 259, 291 Biochemical, 35, 36, 55, 87, 185, 259, 281, 303, 319 Biomarkers, 48, 259 Biopsy, 259, 306 Biosynthesis, 59, 256, 259, 270, 303, 307 Biotechnology, 69, 201, 213, 225, 228, 229, 230, 259 Bladder, 259, 265, 287, 298, 300, 306, 312, 329, 330 Blister, 259, 305 Bloating, 259, 291 Blood Cell Count, 259, 283 Blood Coagulation, 259, 261 Blood Flow Velocity, 70, 156, 259 Blood Glucose, 259, 283, 289 Blood Platelets, 259, 319 Blood Volume, 14, 260 Blood-Brain Barrier, 34, 260 Body Composition, 42, 260 Body Fluids, 259, 260, 261, 274, 321, 329 Body Mass Index, 47, 52, 62, 175, 226, 260, 304 Bolus, 181, 260 Bolus infusion, 260

Index 335

Bone Marrow, 259, 260, 287, 294, 297, 321, 323 Bone scan, 260, 318 Bottle Feeding, 46, 55, 260 Bowel, 254, 260, 273, 288, 302, 306, 323 Bowel Movement, 260, 273, 323 Brachial, 260, 295 Brachial Plexus, 260, 295 Bradycardia, 46, 55, 153, 183, 211, 212, 260 Bradykinin, 260, 301 Brain Stem, 65, 130, 260, 264 Branch, 53, 247, 261, 275, 295, 305, 313, 322, 326 Breakdown, 180, 261, 273, 280 Broadband, 14, 261 Bronchi, 261, 277, 326, 328 Bronchial, 261, 326 Bronchiectasis, 202, 261 Bronchiseptica, 261, 307 Bronchitis, 204, 261, 266 Bronchopulmonary, 54, 261 Bronchopulmonary Dysplasia, 54, 261 Bruxism, 25, 261 Buffers, 258, 261 Bulimia, 152, 153, 183, 261 Bupivacaine, 117, 261 Bupropion, 170, 261 Bypass, 36, 85, 261 C Caffeine, 114, 115, 117, 198, 218, 219, 261 Calcium, 4, 54, 198, 261, 262, 267, 320 Calcium Channels, 54, 261 Calpain, 194, 262 Candidiasis, 205, 262 Candidosis, 262 Cannula, 55, 88, 111, 152, 160, 262 Capsules, 262, 274 Carbachol, 40, 262 Carbohydrate, 116, 262, 281 Carcinogenic, 259, 262, 288, 323 Carcinogens, 262, 302 Carcinoma, 203, 262 Cardiac arrest, 182, 262 Cardiac Output, 151, 258, 262, 323 Cardiomyopathy, 193, 194, 262 Cardiopulmonary, 10, 46, 151, 262 Cardiorespiratory, 19, 28, 74, 262 Cardiovascular disease, 4, 5, 10, 16, 17, 20, 21, 32, 35, 39, 63, 65, 90, 99, 108, 191, 214, 263 Cardiovascular System, 27, 263 Carnitine, 122, 125, 263

Carotid Body, 23, 25, 58, 91, 263, 265 Carotid Sinus, 23, 54, 263, 311 Carpal Tunnel Syndrome, 194, 263 Case report, 7, 77, 86, 95, 102, 107, 118, 126, 263 Case series, 3, 8, 32, 263, 266 Catecholamine, 29, 59, 255, 263, 274, 307 Catheterization, 255, 263, 290 Caudal, 16, 263, 273, 287, 301, 310 Causal, 32, 35, 42, 263 Cause of Death, 26, 263 Cell Adhesion, 16, 31, 263 Cell Adhesion Molecules, 31, 263 Cell Death, 28, 256, 263, 281, 299 Cell Division, 229, 258, 264, 295, 297, 308, 311, 319 Cell membrane, 261, 264, 272, 280, 307 Cell proliferation, 54, 264, 320 Cell Respiration, 264, 297, 316 Cell Survival, 38, 264 Central Nervous System Depressants, 10, 264 Central Nervous System Infections, 264, 283, 285 Centrifugation, 264, 283 Cerebellar, 257, 264, 315, 328 Cerebellum, 264, 279, 309, 315 Cerebral Aqueduct, 264, 279, 306, 326 Cerebral Arteries, 264, 297 Cerebral hemispheres, 258, 260, 264 Cerebral Palsy, 204, 264, 322 Cerebrospinal, 26, 264, 285, 320 Cerebrospinal fluid, 26, 264, 285, 320 Cerebrovascular, 13, 48, 60, 200, 258, 263, 264, 326 Cerebrum, 264, 329 Cervical, 14, 59, 130, 203, 260, 265, 293, 295, 308 Cervical Plexus, 265, 308 Cervix, 265 Chemoreceptor, 21, 22, 26, 54, 58, 265 Chemotactic Factors, 265, 267 Chemotherapy, 153, 184, 265 Chest wall, 29, 145, 265 Child Care, 26, 265 Chin, 81, 122, 123, 143, 265 Choanal Atresia, 205, 265 Cholesteatoma, 199, 265 Cholesterol, 64, 197, 259, 265, 270, 274, 285, 293, 323 Cholinergic, 23, 262, 265, 301

336 Apnea

Cholinesterase Inhibitors, 153, 184, 265, 274 Chromatin, 256, 265, 322 Chromosome, 265, 274, 293, 319 Chronic Disease, 61, 151, 266 Chronic lymphocytic leukemia, 124, 266 Chronic Obstructive Pulmonary Disease, 19, 92, 178, 266 Chronic renal, 6, 10, 266, 309 Circadian, 17, 31, 66, 266 Clamp, 23, 266 Cleft Palate, 90, 94, 203, 266, 330 Clinical Medicine, 266, 310 Clinical series, 100, 266 Clinical trial, 12, 23, 44, 46, 131, 133, 225, 266, 269, 305, 312, 314 Clonazepam, 87, 266 Clonic, 266 Cloning, 140, 141, 259, 266 Coagulation, 17, 259, 266, 284, 292, 326 Coca, 266 Cocaine, 170, 266 Cochlear, 266, 285, 327, 331 Cochlear Diseases, 266, 327 Cofactor, 266, 312 Cognition, 188, 267 Colitis, 267, 288, 291 Collagen, 205, 267, 278, 303, 309, 311 Collapse, 8, 17, 30, 47, 52, 123, 142, 159, 164, 178, 182, 187, 191, 261, 267, 321 Collateral Circulation, 38, 267 Comorbidity, 100, 267 Complement, 57, 254, 267, 280, 319 Complementary and alternative medicine, 121, 127, 267 Complementary medicine, 121, 267 Computational Biology, 225, 228, 268 Computed tomography, 268, 318 Computerized axial tomography, 268, 318 Computerized tomography, 173, 268 Concomitant, 54, 76, 169, 268 Conduction, 151, 268 Confounding, 20, 268 Congestion, 145, 268 Congestive heart failure, 22, 30, 71, 125, 138, 148, 158, 159, 167, 178, 193, 194, 268 Conjugated, 268, 271 Connective Tissue, 260, 267, 268, 278, 280, 294, 306, 317 Conscious Sedation, 110, 268 Consciousness, 254, 255, 268, 271, 272, 273, 325

Constipation, 268, 291, 320 Constitutional, 268, 298 Constriction, 189, 268, 291, 312, 330 Constriction, Pathologic, 268, 330 Consultation, 169, 268 Consumption, 39, 167, 197, 269, 304 Continuum, 42, 269 Contractility, 125, 151, 255, 269 Contraindications, ii, 94, 269 Contralateral, 269, 296, 303, 315 Control group, 46, 48, 269, 311 Controlled study, 57, 269 Convulsions, 255, 258, 269, 286 Coordination, 27, 264, 269, 298 Cor, 21, 56, 158, 167, 269 Cor pulmonale, 56, 158, 167, 269 Coronary, 4, 30, 36, 38, 51, 90, 153, 165, 179, 184, 263, 269, 270, 286, 296, 298 Coronary Arteriosclerosis, 269, 298 Coronary Artery Bypass, 4, 269 Coronary Disease, 4, 269 Coronary heart disease, 263, 269 Coronary Thrombosis, 270, 296, 298 Coronary Vessels, 36, 269, 270 Corpus, 270, 311, 326 Corpus Luteum, 270, 311 Cortex, 44, 53, 55, 68, 257, 264, 270, 276, 277, 278, 297, 299, 310 Cortical, 18, 28, 54, 55, 68, 83, 124, 270, 277, 310, 319, 326 Cortisol, 32, 48, 270 Cost-benefit, 60, 270 Cranial, 264, 270, 278, 282, 286, 290, 291, 301, 302, 303, 305, 306, 315, 330, 331 Craniocerebral Trauma, 258, 270, 283, 285, 326, 327 Craniofacial Abnormalities, 10, 270 Creatinine, 7, 270 Crowding, 11, 270 Cryotherapy, 142, 270 Curative, 139, 270, 301, 326 Cutaneous, 65, 262, 265, 270 Cyclic, 261, 262, 270, 282, 301, 307, 312, 318, 326 Cyst, 71, 205, 270 Cystathionine beta-Synthase, 270, 286 Cytochrome, 43, 270 Cytokine, 34, 66, 188, 271 Cytoplasm, 256, 264, 271, 297, 299, 317, 325 Cytoskeletal Proteins, 262, 271 Cytoskeleton, 271, 297

Index 337

D Data Collection, 33, 62, 271 Databases, Bibliographic, 225, 271 Decision Making, 9, 271 Decompression, 271, 273 Degenerative, 271, 281, 284, 303 Deglutition, 153, 184, 271 Deletion, 39, 141, 256, 271 Delirium, 153, 184, 271 Dementia, 9, 24, 59, 153, 184, 194, 272 Dendrites, 272, 301 Dendritic, 19, 272, 295 Density, 28, 165, 260, 264, 272, 274, 293, 302, 322 Dental Hygienists, 12, 272 Dentate Gyrus, 272, 284 Dentists, 4, 8, 10, 100, 272 Dentition, 6, 272 Depolarization, 54, 145, 272, 320 Depressive Disorder, 170, 272 Deprivation, 31, 67, 68, 193, 194, 272 Diabetes Mellitus, 4, 36, 132, 272, 281, 283, 302 Diabetic Retinopathy, 38, 272, 308 Diagnostic procedure, 135, 157, 213, 272 Diagnostic Services, 272, 326 Dialyzer, 272, 283 Diaphragm, 125, 179, 187, 265, 272, 308, 309, 316 Diarrhea, 272, 291 Diastole, 273 Diastolic, 29, 79, 273, 286 Diencephalon, 273, 287, 305, 310, 326 Diffusion, 273, 329 Digestion, 259, 260, 273, 293, 323 Digestive system, 134, 204, 273 Dilatation, 254, 261, 273, 311, 330 Dilatation, Pathologic, 273, 330 Dilation, 14, 80, 260, 273, 285, 330 Dilator, 17, 25, 37, 159, 168, 179, 273 Dimethyl, 171, 273 Discrimination, 110, 155, 161, 273 Dislocation, 205, 273 Disorientation, 271, 273 Dissociation, 39, 67, 252, 273, 290 Dissociative Disorders, 273 Distal, 160, 258, 269, 273, 275, 280, 311, 312 Diuresis, 261, 273, 326 Diuretic, 151, 273 Diving, 72, 80, 273 Dizziness, 199, 274, 331 Donepezil, 153, 184, 274

Dopamine, 170, 261, 266, 274, 297, 307 Dorsal, 16, 44, 65, 274, 310, 322 Dorsum, 274, 280 Dosage Forms, 170, 274 Down syndrome, 12, 97, 105, 274 Drive, ii, vi, 4, 5, 20, 22, 23, 24, 37, 40, 67, 113, 125, 160, 191, 274, 292 Drug Interactions, 218, 274 Drug Tolerance, 274, 327 Duct, 253, 262, 263, 274, 318 Duodenum, 259, 274, 276, 305, 323 Dyes, 253, 274 Dyslexia, 153, 184, 274 Dyslipidemia, 4, 5, 48, 66, 198, 274 Dysphonia, 199, 274, 332 Dysphoric, 272, 275 Dysplasia, 229, 275 Dyspnea, 203, 275 Dystrophy, 229, 275 E Eardrum, 199, 275 Eating Disorders, 170, 198, 275 Edema, 73, 205, 272, 275, 290 Effector, 251, 267, 275, 300, 301, 307 Effector cell, 275, 300, 301 Efficacy, 8, 34, 37, 52, 63, 81, 87, 109, 123, 131, 132, 169, 171, 185, 275, 293, 328 Elasticity, 172, 269, 275 Elastin, 267, 275 Electrocardiogram, 30, 137, 165, 275 Electrocoagulation, 266, 275 Electrode, 14, 136, 148, 275 Electrolyte, 253, 272, 275, 283, 310, 321 Electrons, 256, 258, 275, 290, 304, 314 Electrophysiological, 53, 275, 331 Embolus, 275, 288 Embryo, 275, 288, 303 Emphysema, 204, 266, 275 Empirical, 63, 275 Endarterectomy, 255, 275 Endocarditis, 262, 276 Endocrine System, 276, 300 Endometrial, 276 Endometriosis, 141, 276 Endometrium, 276, 296 Endoscope, 276, 292 Endoscopic, 82, 205, 276 Endoscopy, 205, 276 Endothelial cell, 260, 276 Endothelium, 276, 301 Endothelium-derived, 276, 301 Endotoxin, 276, 329

338 Apnea

Endotracheal intubation, 79, 276 End-stage renal, 5, 10, 266, 276, 309 Energy balance, 276, 292 Entorhinal Cortex, 276, 284 Environmental Exposure, 276, 302 Environmental Health, 224, 226, 276 Enzymatic, 261, 267, 276, 317 Enzyme, 59, 270, 275, 276, 282, 297, 307, 308, 312, 316, 320, 324, 332 Epidemic, 32, 61, 180, 276, 323 Epidemiological, 35, 277 Epidermis, 251, 259, 277, 305 Epidural, 158, 277 Epinephrine, 16, 252, 274, 277, 301, 329 Erythrocyte Volume, 260, 277 Erythrocytes, 254, 259, 260, 262, 277, 284, 319 Esophageal, 82, 122, 199, 205, 277, 280 Esophagitis, 277, 280 Esophagus, 204, 205, 273, 277, 280, 294, 307, 315, 323 Essential Tremor, 229, 277 Estrogen, 15, 56, 64, 277 Evoke, 20, 277, 323 Evoked Potentials, 122, 277 Excipients, 163, 164, 277 Excitability, 40, 277, 299 Excitation, 52, 253, 265, 277 Excitatory, 19, 21, 23, 51, 277, 281 Exhaustion, 160, 255, 277 Exogenous, 278, 329 Expiration, 29, 147, 160, 174, 178, 278, 279, 316 Expiratory, 29, 140, 166, 174, 178, 278, 279, 307 Expiratory Reserve Volume, 278, 279 Extensor, 278, 313 Extracellular, 40, 141, 253, 257, 268, 278, 296, 300, 321 Extracellular Space, 278, 297 Extraction, 62, 278 Extraocular, 80, 278 Extrapyramidal, 274, 278 Extremity, 260, 278, 295 F Facial, 5, 6, 136, 161, 168, 270, 278, 285, 295, 305, 321 Facial Nerve, 278, 285, 305 Facial Nerve Diseases, 278, 285 Family Planning, 225, 278

Fat, 9, 35, 50, 74, 132, 164, 175, 205, 251, 252, 256, 260, 269, 270, 275, 278, 292, 293, 298, 304, 317, 321 Fatigue, 9, 55, 66, 84, 103, 115, 146, 149, 159, 180, 278, 283, 296 Fatty acids, 278, 312 Fetus, 71, 278, 308, 330 Fibroblasts, 278, 289 Fibrosis, 203, 229, 278, 318 Fissure, 266, 272, 278, 310 Fistula, 199, 278, 302 Fixation, 278, 319 Flatus, 279, 280 Fluoroscopy, 11, 279 Flutter, 182, 279 Fold, 63, 100, 203, 205, 278, 279, 296, 304 Foramen, 265, 279, 295, 306 Forearm, 67, 260, 279, 295 Fourth Ventricle, 264, 279, 293, 326 Friction, 253, 279 Frontal Lobe, 153, 184, 279, 298, 310 Functional magnetic resonance imaging, 18, 68, 279 Functional Residual Capacity, 96, 279 Fungus, 262, 279 G GABA, 37, 40, 266, 279, 320 Gallbladder, 251, 273, 279 Gamma-interferon, 279, 289 Ganglia, 251, 258, 280, 300, 306, 324 Ganglion, 16, 19, 59, 280, 301, 303, 331 Gap Junctions, 280, 325 Gas, 108, 138, 139, 140, 152, 162, 166, 167, 172, 174, 177, 178, 188, 195, 199, 262, 273, 279, 280, 285, 291, 301, 313, 316, 324, 331 Gas exchange, 280, 313, 316, 331 Gastric, 55, 85, 168, 203, 263, 274, 280 Gastrin, 280, 284 Gastroesophageal Reflux, 92, 95, 99, 193, 194, 204, 280 Gastroesophageal Reflux Disease, 193, 194, 204, 280 Gastrointestinal, 175, 194, 260, 265, 277, 280, 319, 321, 322, 324, 329 Gastrointestinal tract, 194, 265, 280, 319, 322, 329 Gels, 59, 280 Gene, 21, 28, 31, 36, 48, 58, 64, 192, 201, 230, 231, 259, 280, 302, 308, 319 Gene Expression, 21, 28, 48, 58, 230, 280

Index 339

Generator, 24, 136, 138, 147, 162, 174, 191, 280 Genetic Code, 280, 302 Genetic Engineering, 259, 266, 280 Genetic Techniques, 40, 281 Genetics, 35, 49, 86, 129, 281 Genomics, 59, 281 Genotype, 13, 53, 281, 307 Germ Cells, 281, 295, 304, 322, 326 Gestation, 203, 281, 306, 308 Gestational, 198, 281 Giant Cells, 281, 318 Gland, 59, 141, 252, 281, 285, 294, 304, 305, 308, 312, 319, 323, 324, 327 Gliosis, 85, 91, 281 Glomerular, 281, 316 Glossectomy, 92, 281 Glottis, 281, 307 Glucose, 6, 20, 32, 132, 156, 198, 203, 229, 259, 272, 281, 283, 286, 289, 308, 318 Glucose Intolerance, 32, 272, 281 Glucose tolerance, 20, 32, 132, 198, 281 Glucose Tolerance Test, 198, 281 Glutamate, 26, 53, 281 Glutamic Acid, 281, 284, 311 Glycoprotein, 281, 329 Goats, 25, 282 Gonad, 282 Gonadal, 15, 77, 141, 282, 323 Gonadorelin, 282, 292 Gonadotropin, 140, 141, 282, 292 Governing Board, 282, 310 Grade, 61, 282 Graft, 153, 184, 282, 285 Grafting, 269, 282 Granulomas, 205, 282 Gravis, 153, 184, 194, 282 Growth, 5, 19, 38, 46, 49, 56, 76, 87, 122, 139, 185, 229, 236, 252, 254, 255, 256, 258, 263, 264, 282, 289, 294, 300, 302, 308, 318, 322, 327, 329 Guanylate Cyclase, 282, 301 H Habitual, 182, 282 Hair Cells, 282, 295 Hallucinogens, 282, 313 Halogens, 162, 282 Haptens, 252, 282 Headache, 148, 261, 282, 283, 285, 286, 311, 320, 330 Headache Disorders, 283 Health Behavior, 62, 283

Health Policy, 214, 283 Health Services, 114, 116, 117, 201, 208, 283, 326 Health Status, 48, 74, 283 Heart attack, 9, 164, 186, 263, 283 Heartbeat, 136, 137, 147, 161, 174, 212, 283 Hematocrit, 156, 259, 283 Heme, 270, 283 Hemicrania, 283, 330 Hemodiafiltration, 283, 329 Hemodialysis, 4, 6, 10, 109, 272, 283, 291, 329 Hemodynamics, 14, 105, 283 Hemofiltration, 283, 329 Hemoglobin, 4, 14, 35, 84, 147, 152, 156, 254, 259, 277, 283, 284, 304 Hemoglobin C, 35, 254, 284 Hemoglobinuria, 229, 284 Hemorrhage, 183, 205, 270, 275, 282, 284, 323, 332 Hemostasis, 284, 320 Hepatic, 132, 272, 281, 284 Hepatitis, 284, 288 Hepatomegaly, 284, 288 Hereditary, 284, 317 Heredity, 280, 281, 284 Heritability, 35, 284 Heterogeneity, 38, 252, 284 Hippocampus, 53, 272, 284, 292, 324 Hirsutism, 141, 284, 285, 286 Hoarseness, 199, 204, 284, 292 Homeostasis, 19, 27, 28, 32, 198, 284, 321 Homogeneous, 269, 284, 307 Homologous, 284, 298, 319, 325 Hormonal, 64, 257, 284, 306 Hormone Replacement Therapy, 15, 42, 57, 284 Host, 141, 159, 258, 262, 285, 287, 331 Hybridomas, 285, 289 Hydrocephalus, 285, 290 Hydrogen, 251, 258, 261, 262, 285, 293, 297, 304, 324 Hydrogen Peroxide, 285, 293, 324 Hydrolysis, 141, 285, 309, 312 Hydroxylysine, 267, 285 Hydroxyproline, 267, 285 Hyperacusis, 199, 278, 285 Hyperalgesia, 65, 285 Hyperandrogenism, 64, 285 Hyperbilirubinemia, 285, 291 Hypercapnia, 17, 22, 29, 78, 79, 89, 285, 308

340 Apnea

Hypercholesterolemia, 274, 285 Hyperglycemia, 5, 285 Hyperhomocysteinemia, 4, 270, 285 Hyperlipidemia, 36, 132, 274, 286 Hyperpnea, 40, 286 Hypersensitivity, 253, 286, 317, 319 Hypersensitivity, Immediate, 286 Hypertension, Pulmonary, 9, 286 Hyperthermia, 142, 286 Hypertrichosis, 284, 286 Hypertriglyceridemia, 274, 286 Hypertrophy, 93, 141, 142, 205, 210, 269, 286, 328 Hyperventilation, 22, 24, 122, 150, 179, 286 Hypnotherapy, 122, 286 Hypnotic, 56, 258, 286 Hypnotics and Sedatives, 264, 286 Hypocapnia, 22, 286 Hypoglossal Nerve, 14, 47, 110, 148, 286 Hypoglycaemia, 272, 286 Hypopharynx, 97, 286 Hypotension, 4, 65, 188, 269, 286 Hypothalamic, 37, 287 Hypothalamus, 21, 25, 37, 44, 141, 258, 273, 282, 287, 292, 308, 311, 322, 326 Hypotonia, 188, 287 Hypoventilation, 19, 25, 28, 47, 150, 193, 287, 308 Hypoxemia, 20, 23, 27, 32, 35, 107, 287 I Iatrogenic, 203, 287 Id, 118, 126, 143, 164, 182, 235, 237, 239, 246, 248, 287 Idiopathic, 212, 287, 318 Illusion, 287, 331 Immune response, 252, 256, 257, 282, 287, 319, 324, 331 Immune Sera, 287 Immunization, 211, 287, 311, 319 Immunodeficiency, 229, 287 Immunohistochemistry, 16, 29, 287 Immunologic, 265, 287 Immunology, 101, 252, 287 Impairment, 20, 32, 56, 76, 98, 154, 188, 194, 204, 257, 271, 274, 287, 296 Impotence, 199, 287, 332 In vitro, 19, 21, 24, 38, 185, 287 In vivo, 19, 21, 24, 25, 28, 38, 43, 89, 185, 287, 296 Incision, 287, 290, 328 Incompetence, 280, 287 Incontinence, 152, 170, 183, 285, 287

Incubation, 288, 307 Incubation period, 288, 307 Indicative, 137, 146, 168, 173, 186, 199, 288, 305, 330 Induction, 25, 34, 91, 254, 288 Inertia, 138, 288 Infancy, 28, 54, 288 Infant, Newborn, 252, 288 Infantile, 201, 202, 207, 288 Infarction, 165, 285, 288, 316 Infection, 203, 204, 251, 262, 265, 271, 287, 288, 294, 301, 305, 307, 317, 324, 332 Infectious Mononucleosis, 205, 288 Inflammatory bowel disease, 38, 288 Informed Consent, 30, 288 Infusion, 67, 288, 328 Ingestion, 281, 288, 309 Inhalation, 137, 152, 172, 204, 288, 309 Initiation, 37, 60, 288, 328 Inlay, 288, 317 Inner ear, 266, 289, 291 Innervation, 260, 278, 286, 289, 295 Inositol, 141, 289, 318 Inotropic, 274, 289 Insight, 20, 50, 59, 67, 289 Insomnia, 39, 42, 106, 127, 188, 238, 289, 311, 320 Insulator, 289, 298 Insulin, 5, 21, 32, 48, 64, 66, 91, 132, 186, 210, 281, 289, 329 Insulin-dependent diabetes mellitus, 289 Intensive Care, 18, 151, 173, 174, 289 Intensive Care Units, 18, 174, 289 Intercellular Adhesion Molecule-1, 34, 289 Intercostal, 289, 316 Interferometry, 146, 173, 289 Interindividual, 38, 289 Interleukin-1, 33, 289 Interleukin-2, 289 Interleukin-6, 66, 81, 90, 289 Internal Medicine, 77, 95, 110, 116, 290, 295, 300 Interstitial, 142, 278, 290, 316 Intestinal, 92, 281, 290, 294 Intestines, 251, 280, 290, 319 Intoxication, 271, 290, 332 Intracellular, 25, 40, 54, 141, 261, 281, 288, 290, 301, 310, 312, 315, 318, 320 Intracranial Hypertension, 212, 283, 285, 290, 327 Intraocular, 290, 327 Intraocular pressure, 290, 327

Index 341

Intrathecal, 117, 290 Intravenous, 117, 288, 290 Intrinsic, 49, 64, 146, 149, 192, 252, 290 Intubation, 130, 203, 263, 290 Invasive, 4, 13, 35, 41, 44, 146, 156, 168, 173, 174, 290, 294, 304 Involuntary, 258, 277, 290, 299, 315, 321, 322 Ion Channels, 257, 290, 300, 301, 325 Ion Exchange, 290 Ionization, 290 Ions, 258, 261, 262, 273, 275, 285, 290 Iontophoresis, 25, 290 Irritable Bowel Syndrome, 141, 152, 170, 183, 291 Ischemia, 36, 38, 189, 257, 291, 316 Ischemic stroke, 9, 291 J Jaundice, 156, 285, 291 Joint, 5, 8, 61, 81, 257, 291, 294, 303, 325 K Kb, 224, 291 Kidney Disease, 4, 134, 224, 229, 291 Kidney Failure, 276, 291 Kidney stone, 291, 329 Kinetics, 262, 291 L Labile, 267, 291 Labyrinth, 289, 291, 303, 306, 331 Labyrinthitis, 199, 291 Large Intestine, 273, 290, 291, 315, 321 Laryngeal, 29, 44, 125, 199, 203, 205, 291, 315 Laryngeal Diseases, 199, 291 Laryngeal Nerves, 291, 315 Laryngitis, 204, 292 Laryngoscopy, 205, 292 Larynx, 97, 188, 204, 281, 286, 291, 292, 315, 328, 330, 332 Laser Surgery, 211, 292 Latency, 28, 49, 57, 292 Latent, 292, 310 Legionellosis, 202, 292 Leptin, 21, 32, 47, 63, 74, 292 Lesion, 114, 269, 281, 292, 293 Lethal, 160, 292 Leukemia, 229, 292 Leukocytes, 259, 260, 265, 292, 297, 329 Leuprolide, 64, 292 Libido, 148, 254, 292 Library Services, 246, 292 Ligament, 292, 312

Ligands, 193, 263, 292 Light microscope, 292, 297 Limbic, 253, 292, 310 Limbic System, 253, 292, 310 Linkages, 35, 283, 293 Lip, 142, 293 Lipid, 48, 63, 117, 289, 293, 298, 304 Lipid Peroxidation, 293, 304 Lipoma, 102, 107, 293 Lipoprotein, 274, 293 Liver, 194, 251, 256, 259, 262, 263, 273, 279, 281, 284, 293, 316, 318 Liver scan, 293, 318 Lobe, 150, 293 Localization, 36, 68, 115, 287, 293 Localized, 57, 106, 254, 279, 284, 286, 288, 293, 308 Locus Coeruleus, 44, 293 Longitudinal study, 41, 293 Long-Term Potentiation, 53, 293 Loop, 108, 148, 293 Lordosis, 293, 306 Low-density lipoprotein, 274, 293 Lower Esophageal Sphincter, 280, 294 Lumen, 262, 294 Luxation, 273, 294 Lymph, 265, 276, 288, 294, 318, 324 Lymph node, 265, 294, 318 Lymphadenopathy, 288, 294 Lymphatic, 102, 276, 288, 294, 321, 323, 327 Lymphocytic, 294 Lymphoid, 255, 294, 327 Lymphoma, 125, 229, 294 Lysine, 284, 285, 294 M Macrophage, 289, 294 Magnetic Resonance Imaging, 36, 50, 52, 110, 173, 174, 294, 318 Malabsorption, 92, 229, 294 Malaise, 188, 294 Malformation, 102, 294 Malignant, 229, 294, 300 Malnutrition, 4, 257, 294, 298 Mammary, 269, 294 Mandible, 4, 7, 9, 154, 182, 265, 294 Mania, 153, 184, 294 Manifest, 53, 258, 294 Mastication, 55, 295 Maxillary, 139, 295, 305 Meatus, 275, 295, 303, 330 Mechanical ventilation, 22, 261, 295

342 Apnea

Mechanoreceptors, 22, 282, 295 Medial, 53, 295, 302, 317 Median Nerve, 194, 263, 295 Mediate, 21, 25, 48, 263, 274, 295 Mediator, 289, 295, 320 Medical Oncology, 49, 125, 295 Medical Records, 295, 317 Medicament, 176, 295 MEDLINE, 225, 228, 230, 295 Medullary, 24, 25, 27, 37, 40, 57, 153, 184, 295 Meiosis, 295, 298, 325 Melanin, 293, 295, 307, 329 Melanocytes, 295 Melanoma, 229, 295 Meninges, 264, 265, 270, 296 Menopause, 41, 56, 115, 296, 310 Menstrual Cycle, 296, 311 Menstruation, 296, 310 Mental Disorders, 134, 296, 311, 313 Mental Fatigue, 82, 296 Mental Health, iv, 12, 134, 224, 227, 296, 311, 313 Mental Processes, 273, 296, 313 Mental Retardation, 231, 274, 296 Mentors, 34, 296 Mesencephalic, 57, 293, 296, 315 Mesenteric, 51, 296 Mesentery, 296, 307 Meta-Analysis, 77, 296 Metabolite, 57, 170, 273, 296 Metastasis, 185, 263, 296 Methionine, 273, 296 MI, 28, 62, 125, 147, 175, 182, 198, 249, 296 Microbiology, 251, 257, 296 Microcirculation, 43, 73, 296 Microdialysis, 25, 296 Microorganism, 266, 297, 332 Microscopy, 16, 297 Microsurgery, 205, 297 Microtubules, 26, 297 Middle Cerebral Artery, 189, 297 Migration, 181, 289, 297, 300 Mitochondria, 43, 297, 303 Mitosis, 256, 297 Mobility, 51, 158, 297 Modeling, 24, 297 Modification, 96, 116, 121, 124, 169, 280, 297, 314 Modulator, 19, 297

Molecule, 16, 33, 188, 256, 258, 267, 273, 275, 276, 277, 285, 297, 304, 308, 315, 320, 330 Monoamine, 25, 171, 255, 297 Monocytes, 48, 289, 292, 297 Mononuclear, 288, 297, 329 Morphine, 188, 297, 299, 302 Morphological, 55, 275, 279, 295, 297 Morphology, 6, 55, 62, 74, 297 Motility, 298, 320 Motor Activity, 30, 87, 269, 298 Motor Cortex, 55, 298, 315 Motor nerve, 298, 302, 308 Motor Neurons, 52, 298 Mucinous, 280, 298 Mucociliary, 298, 320 Mucosa, 211, 298, 299 Multiple sclerosis, 153, 184, 298 Multivalent, 282, 298 Muscle Fibers, 298, 299 Muscle relaxant, 255, 298, 324 Muscle Relaxation, 173, 298, 324 Muscular Atrophy, 229, 298 Muscular Dystrophies, 275, 298 Musculature, 40, 298 Myasthenia, 153, 184, 194, 298 Mydriatic, 273, 298, 332 Myelin, 298, 300 Myocardial infarction, 9, 17, 28, 38, 270, 296, 298, 299 Myocardial Ischemia, 36, 269, 298 Myocardium, 151, 161, 296, 298, 299 Myofibrils, 262, 299 Myopathy, 153, 184, 299 Myosin, 55, 299 Myotonic Dystrophy, 229, 299 N Nadir, 51, 299 Narcolepsy, 39, 97, 170, 188, 299 Narcosis, 299 Narcotic, 169, 188, 297, 299 Nasal Cavity, 139, 299, 305, 329 Nasal Obstruction, 44, 142, 204, 299 Nasal Septum, 299 Nasogastric, 55, 299 Nasopharyngitis, 205, 299 Nasopharynx, 299 Natriuresis, 255, 299 Nausea, 274, 299, 311, 312, 329 NCI, 1, 133, 185, 223, 299 Necrosis, 256, 288, 296, 298, 299, 316, 318 Neocortex, 28, 299

Index 343

Neonatal, 29, 47, 98, 115, 116, 117, 137, 208, 237, 300 Neoplasia, 229, 300 Neoplasm, 300, 329 Neoplastic, 185, 254, 265, 285, 294, 300 Nephrology, 10, 300 Nephropathy, 291, 300 Nerve Endings, 54, 300 Networks, 203, 300 Neural, 16, 20, 24, 25, 27, 28, 43, 44, 55, 67, 98, 151, 203, 252, 253, 295, 300, 306 Neuroeffector Junction, 300 Neuroendocrine, 31, 300 Neuroendocrinology, 31, 300 Neurogenic, 58, 300 Neuroglia, 281, 300 Neurologic, 132, 153, 158, 184, 193, 255, 285, 300 Neurology, 32, 68, 76, 300 Neuromuscular, 12, 47, 55, 110, 251, 300, 330 Neuromuscular Junction, 251, 300 Neuronal, 23, 25, 27, 38, 54, 57, 65, 141, 171, 188, 262, 299, 300, 301, 306 Neuropathy, 170, 194, 211, 301 Neuropeptides, 262, 301 Neurophysiology, 272, 301 Neurotoxic, 26, 301 Neurotoxin, 26, 301 Neurotransmitters, 40, 54, 301, 311, 320, 321 Neutrophil, 289, 301 Niacin, 301, 329 Nicotine, 75, 170, 301 Nitric Oxide, 33, 58, 67, 188, 301 Nitrogen, 253, 254, 279, 301, 329 Nocturia, 6, 98, 99, 104, 301 Nodose, 16, 19, 291, 301 Nodose Ganglion, 16, 291, 301 Norepinephrine, 67, 171, 252, 274, 301, 320 Normotensive, 67, 301 Nuclear, 123, 258, 275, 280, 292, 299, 302, 326 Nuclei, 15, 24, 26, 253, 275, 278, 280, 292, 294, 297, 302, 303, 331 Nucleic acid, 141, 280, 301, 302 Nurse Practitioners, 47, 302 O Observational study, 59, 302 Occipital Lobe, 150, 302 Occult, 42, 102, 302 Octreotide, 194, 302

Oculomotor, 296, 302 Office Visits, 5, 302 Ointments, 274, 302 Oncogene, 229, 302 Oncology, 48, 125, 302 On-line, 50, 249, 302 Opacity, 272, 302 Opium, 297, 302 Optic Chiasm, 287, 302, 303, 311 Optic cup, 303, 305 Optic Disk, 272, 303 Optic Nerve, 302, 303, 305, 313, 317 Oral Health, 12, 202, 303 Orbit, 303 Orbital, 44, 80, 303 Organelles, 264, 271, 295, 297, 303 Oropharynx, 286, 303 Orthostatic, 16, 302, 303 Ossicles, 303, 323 Ossification, 303 Osteoarthritis, 170, 185, 303 Osteogenesis, 92, 95, 303 Osteogenesis Imperfecta, 92, 303 Osteotomy, 11, 303 Otitis, 199, 303 Otitis Media, 199, 303 Otolaryngology, 70, 92, 93, 102, 107, 109, 118, 200, 205, 234, 235, 236, 303 Otosclerosis, 199, 303 Outer ear, 199, 303 Outpatient, 8, 304 Ovaries, 285, 304, 320 Ovary, 64, 141, 270, 282, 285, 304 Overweight, 48, 61, 118, 175, 226, 304 Ovum, 270, 281, 304, 311, 332 Oxidation, 188, 251, 256, 270, 282, 293, 304 Oxidation-Reduction, 188, 304 Oxidative Stress, 43, 48, 74, 117, 304 Oximetry, 42, 44, 59, 67, 102, 156, 191, 304 Oxygen Consumption, 304, 316 Oxygenation, 13, 36, 59, 67, 163, 180, 287, 304 P Pacemaker, 136, 179, 304 Palate, 8, 9, 88, 90, 94, 97, 118, 142, 143, 144, 155, 163, 203, 266, 299, 304, 321, 330 Palliative, 304, 326 Palsy, 153, 184, 304 Pancreas, 251, 259, 273, 289, 304, 305, 322, 329 Pancreatic, 229, 263, 280, 304, 305 Pancreatic cancer, 229, 305

344 Apnea

Pancreatic Juice, 280, 305 Paralysis, 100, 205, 296, 305, 322 Paranasal Sinuses, 305, 320 Parietal, 68, 305, 306, 309 Parietal Lobe, 305 Parotid, 305, 318 Paroxysmal, 229, 283, 305, 307, 330, 332 Particle, 305, 322, 328 Patch, 23, 305 Pathogenesis, 29, 50, 58, 104, 158, 168, 198, 200, 305 Pathologic, 116, 251, 256, 259, 262, 269, 285, 286, 305, 310, 313 Pathologic Processes, 256, 305 Pathologies, 142, 305 Pathophysiology, 17, 29, 35, 52, 305 Patient Advocacy, 214, 305 Patient Compliance, 168, 305 Patient Education, 236, 244, 246, 249, 305 Patient Selection, 205, 305 Pedicle, 205, 305 Pelvic, 276, 305, 312 Pemphigus, 205, 251, 305 Penicillin, 255, 305 Peptide, 21, 30, 292, 305, 309, 312 Perception, 103, 203, 204, 282, 305, 318 Percutaneous, 4, 306, 307 Perfusion, 22, 44, 287, 306 Periaqueductal Gray, 25, 306 Perilymph, 199, 306 Perinatal, 114, 116, 117, 207, 306 Periodicity, 59, 89, 306 Periodontitis, 185, 306 Perioperative, 114, 172, 306 Peripheral Nerves, 194, 306, 322 Peripheral Nervous System, 304, 306, 311, 322, 324 Peripheral Vascular Disease, 162, 306 Peritoneal, 4, 6, 10, 306 Peritoneal Cavity, 306 Peritoneal Dialysis, 4, 6, 10, 306 Peritoneum, 296, 306 Pertussis, 141, 307, 332 Pharmaceutical Solutions, 274, 307 Pharmacologic, 29, 40, 44, 72, 116, 168, 254, 307, 327 Pharmacotherapy, 52, 307 Pharyngeal Muscles, 53, 307 Pharyngitis, 205, 307 Pharynx, 8, 9, 11, 45, 93, 142, 173, 180, 191, 205, 280, 286, 299, 303, 307, 330 Phenotype, 35, 307

Phenyl, 162, 307 Phenylalanine, 307, 329 Phonation, 204, 307 Phonophoresis, 290, 307 Phosphodiesterase, 170, 307 Phosphodiesterase Inhibitors, 170, 307 Phospholipids, 278, 289, 293, 307 Phosphorus, 261, 307 Phosphorylase, 262, 308 Photocoagulation, 266, 308 Phrenic Nerve, 179, 308 Physical Examination, 8, 72, 205, 308 Physiology, 24, 25, 26, 31, 36, 45, 79, 80, 81, 84, 85, 91, 98, 103, 106, 107, 123, 124, 125, 126, 275, 300, 301, 308 Pickwickian Syndrome, 160, 308 Pigment, 295, 308 Pilot study, 115, 308 Pitch, 204, 308, 332 Pituitary Gland, 141, 282, 308 Placenta, 308, 311 Plants, 253, 262, 266, 281, 297, 301, 308, 318, 327 Plaque, 254, 308 Plasma, 31, 48, 64, 66, 90, 103, 117, 255, 260, 264, 281, 283, 284, 291, 308, 316, 319 Plasma cells, 255, 308 Plasma Volume, 260, 308 Plasticity, 15, 19, 284, 308 Platelet Activation, 89, 309, 320 Platelet Aggregation, 254, 301, 309 Platelets, 262, 301, 309, 326 Platinum, 293, 309 Plethysmograph, 59, 172, 309 Plethysmography, 144, 309 Pleura, 203, 309 Pleural, 203, 309 Pleural cavity, 309 Pleural Effusion, 203, 309 Poisoning, 104, 271, 290, 299, 309 Polycystic, 64, 141, 229, 285, 309 Polymers, 163, 309, 312 Polymorphic, 141, 272, 309 Polypeptide, 253, 267, 309, 322 Polyuria, 6, 99, 309 Pons, 27, 40, 44, 260, 279, 309 Pontine, 24, 27, 40, 57, 278, 309 Port, 160, 174, 177, 310 Port-a-cath, 310 Positive pressure ventilation, 97, 174, 195, 310

Index 345

Posterior, 11, 25, 37, 68, 180, 188, 254, 257, 264, 274, 302, 304, 310, 330 Postmenopausal, 57, 310 Postnatal, 19, 28, 29, 40, 54, 55, 65, 310 Postoperative, 3, 6, 117, 160, 174, 203, 310 Postoperative Complications, 160, 310 Postprandial, 198, 310 Postsynaptic, 19, 40, 300, 310, 320, 325 Potassium, 197, 253, 310 Potentiate, 32, 310 Potentiation, 22, 53, 265, 293, 310, 320 Practicability, 310, 328 Practice Guidelines, 227, 237, 310 Preclinical, 33, 170, 310 Precursor, 12, 256, 274, 275, 276, 301, 307, 310, 329 Predisposition, 67, 83, 310 Prefrontal Cortex, 68, 310 Premenstrual, 141, 170, 310, 311 Premenstrual Syndrome, 141, 170, 311 Preoptic Area, 37, 311 Pressoreceptors, 258, 311 Presynaptic, 40, 300, 311, 325 Presynaptic Terminals, 300, 311, 325 Prevalence, 5, 10, 22, 23, 35, 41, 46, 53, 55, 88, 104, 133, 212, 311 Primary endpoint, 19, 311 Primary Prevention, 30, 311 Probe, 17, 47, 68, 296, 311 Progeny, 13, 311 Progesterone, 15, 56, 311, 323 Progression, 35, 41, 55, 90, 255, 311 Progressive, 47, 153, 164, 184, 266, 272, 274, 282, 298, 299, 303, 309, 311, 316, 329 Projection, 301, 303, 310, 311, 315 Proline, 267, 285, 311 Prone, 37, 91, 144, 165, 178, 181, 311 Prophase, 298, 311, 325 Prophylaxis, 163, 187, 272, 311 Proportional, 63, 158, 311 Prospective Studies, 33, 312 Prospective study, 11, 60, 293, 312 Prostaglandin, 255, 312 Prostate, 141, 142, 229, 259, 312, 329 Prosthesis, 11, 312 Prosthodontics, 154, 312 Protein S, 141, 201, 230, 259, 280, 312, 317 Proteolytic, 267, 312 Protocol, 9, 37, 46, 56, 183, 312 Proximal, 141, 160, 189, 273, 299, 311, 312 Pseudotumor Cerebri, 290, 312 Psoriasis, 188, 313

Psychiatric, 39, 153, 169, 184, 296, 313, 321 Psychic, 292, 313, 319 Psychology, 28, 122, 170, 273, 313 Psychomotor, 271, 313 Psychotropic, 176, 313 Psychotropic Drugs, 176, 313 Puberty, 141, 204, 313 Public Health, 26, 29, 31, 32, 35, 41, 62, 66, 165, 201, 202, 214, 227, 313 Public Policy, 225, 313 Publishing, 3, 4, 5, 9, 69, 197, 204, 205, 313 Pulmonary Alveoli, 287, 313 Pulmonary Artery, 260, 313, 331 Pulmonary Circulation, 58, 286, 313 Pulmonary Edema, 152, 203, 291, 313 Pulmonary hypertension, 56, 58, 73, 93, 105, 269, 308, 313 Pulmonary Ventilation, 286, 313, 316 Pulsation, 279, 313 Pulse, 30, 44, 46, 111, 136, 145, 150, 156, 179, 180, 191, 192, 297, 304, 313 Pupil, 273, 298, 314 Purulent, 251, 314, 330 Q Quality of Life, 5, 10, 17, 18, 33, 35, 43, 48, 56, 60, 95, 98, 106, 129, 314 Quaternary, 314, 324 R Race, 32, 60, 170, 197, 297, 314 Radiation, 270, 274, 276, 286, 314, 318, 332 Radiation therapy, 274, 314 Radioactive, 260, 285, 290, 293, 302, 314, 318 Radiography, 7, 254, 314 Radiological, 306, 314 Radiopharmaceutical, 280, 314 Rage, 306, 314 Randomized, 18, 22, 24, 33, 34, 42, 60, 63, 64, 70, 77, 88, 105, 125, 226, 275, 314 Randomized clinical trial, 60, 314 Randomized Controlled Trials, 34, 314 Raphe Nuclei, 24, 26, 314 Reactive Oxygen Species, 21, 315 Reagent, 315, 321 Receptors, Serotonin, 315, 320 Recombinant, 141, 315, 330 Recovery Room, 173, 315 Rectum, 260, 273, 279, 280, 288, 291, 312, 315 Recur, 192, 306, 315 Recurrence, 100, 306, 315 Recurrent Laryngeal Nerve, 203, 315

346 Apnea

Red Nucleus, 257, 315 Refer, 1, 195, 267, 274, 279, 293, 315, 331 Reflex, 20, 47, 51, 121, 151, 306, 315 Reflux, 85, 86, 193, 194, 280, 315 Refraction, 315, 322 Refractory, 32, 170, 275, 315 Regimen, 151, 167, 168, 275, 305, 307, 315 Regurgitation, 280, 315 Relaxant, 315, 324 Reliability, 34, 49, 315 Remission, 315, 316 Renal failure, 7, 272, 316 Renin, 255, 316 Renin-Angiotensin System, 255, 316 Reperfusion, 36, 316 Reperfusion Injury, 316 Research Support, 34, 316 Residual Volume, 279, 316 Respiration Disorders, 172, 316 Respirator, 187, 194, 295, 310, 316, 331 Respiratory distress syndrome, 33, 203, 261, 316 Respiratory failure, 39, 169, 203, 316, 331 Respiratory Muscles, 22, 195, 316 Respiratory Physiology, 74, 87, 108, 109, 316, 330 Respiratory System, 147, 157, 171, 172, 191, 204, 298, 316 Response rate, 33, 317 Restless legs, 238, 317 Restoration, 47, 147, 312, 316, 317, 332 Reticular, 37, 317 Retina, 272, 300, 302, 303, 317 Retinal, 272, 303, 317 Retinoblastoma, 229, 317 Retractor, 45, 53, 317 Retrospective, 3, 32, 104, 317 Retrospective study, 104, 317 Rheumatism, 317 Rheumatoid, 38, 317 Rheumatoid arthritis, 38, 317 Rhinitis, 199, 204, 261, 317 Ribose, 251, 317 Ribosome, 317, 328 Risk factor, 5, 10, 20, 28, 30, 31, 32, 35, 36, 46, 47, 50, 55, 60, 62, 65, 74, 108, 116, 138, 185, 197, 214, 286, 312, 317 Risk patient, 205, 317 Rod, 258, 266, 317 S Sagittal, 44, 317 Saliva, 117, 317, 318

Salivary, 199, 273, 278, 305, 317, 318, 324, 332 Salivary glands, 199, 273, 278, 317, 318 Salivation, 8, 318 Saphenous, 269, 318 Saphenous Vein, 269, 318 Saponins, 318, 323 Sarcoidosis, 115, 203, 318 Scans, 44, 318 Schizoid, 318, 332 Schizophrenia, 153, 184, 318, 332 Schizotypal Personality Disorder, 318, 332 Sclerae, 303, 318 Sclerosis, 194, 229, 298, 318 Screening, 13, 15, 31, 33, 42, 45, 79, 141, 171, 185, 266, 318 Second Messenger Systems, 301, 318 Secondary tumor, 296, 318 Secretion, 32, 67, 76, 77, 282, 285, 289, 302, 318, 319 Secretory, 66, 300, 319, 325 Sedative, 56, 258, 319 Segmental, 4, 319 Segmentation, 319 Segregation, 35, 86, 319 Seizures, 32, 266, 271, 305, 319 Selection Bias, 10, 319 Self-Help Groups, 240, 319 Sella, 274, 308, 319 Semen, 312, 319 Sensibility, 254, 285, 319 Sensitization, 60, 319 Sensory Deprivation, 121, 319 Sequencing, 319, 325 Serotonin, 15, 26, 169, 171, 188, 189, 307, 315, 319, 320, 324, 329 Serous, 58, 276, 309, 320 Serum, 6, 7, 32, 74, 81, 107, 117, 254, 267, 282, 287, 294, 320, 329 Sex Characteristics, 252, 254, 313, 320, 326 Sex Determination, 229, 320 Shock, 153, 176, 184, 188, 320, 328 Shunt, 138, 320 Sibutramine, 170, 320 Side effect, 7, 49, 115, 159, 168, 185, 198, 211, 217, 219, 252, 274, 320, 327 Signal Transduction, 289, 320 Signs and Symptoms, 8, 9, 205, 316, 320 Sinusitis, 199, 202, 204, 320 Skeletal, 55, 67, 77, 102, 254, 265, 266, 287, 298, 299, 320, 322, 324 Skeleton, 203, 251, 291, 312, 320, 321

Index 347

Skull, 265, 270, 303, 321, 326 Sleep Apnea Syndromes, 122, 131, 132, 133, 200, 321 Sleep Deprivation, 31, 32, 66, 68, 236, 321 Sleep Stages, 13, 56, 80, 321 Small intestine, 274, 284, 290, 299, 321 Smooth muscle, 253, 254, 261, 262, 286, 297, 316, 321, 322, 324 Sneezing, 307, 321 Social Environment, 314, 321 Sodium, 57, 172, 197, 253, 299, 321 Sodium Cyanide, 57, 321 Soft tissue, 50, 138, 155, 159, 168, 182, 191, 203, 260, 320, 321 Solid tumor, 254, 321 Solitary Nucleus, 258, 321 Somatic, 252, 292, 295, 297, 306, 310, 321, 330 Somatostatin, 193, 194, 302, 322 Somnolence, 17, 138, 177, 308, 322 Sound wave, 268, 322 Spasm, 296, 322 Spasmodic, 199, 307, 322 Spastic, 291, 322 Spatial disorientation, 274, 322 Specialist, 8, 214, 240, 273, 322 Species, 26, 141, 277, 295, 297, 314, 315, 322, 324, 328, 329, 331, 332 Specificity, 252, 262, 322 Spectrometer, 59, 322 Spectrum, 7, 155, 322 Sperm, 254, 265, 322, 329 Spermatogenesis, 141, 322 Spermatozoa, 319, 322 Sphincter, 292, 322, 330 Spinal cord, 65, 189, 257, 260, 264, 265, 277, 280, 290, 295, 296, 300, 301, 306, 315, 322, 324 Spinal Nerves, 306, 322 Spirochete, 323, 325 Spleen, 294, 318, 323 Splenomegaly, 288, 323 Splint, 8, 105, 145, 178, 210, 323 Sporadic, 317, 323 Squamous, 265, 323 Squamous Epithelium, 265, 323 Staging, 3, 318, 323 Stapes, 285, 323 Steatosis, 132, 323 Steel, 266, 323 Steroid, 141, 270, 318, 323 Stimulant, 218, 261, 323

Stimulus, 22, 59, 136, 269, 274, 275, 277, 289, 290, 292, 315, 323, 326 Stomach, 204, 251, 273, 277, 280, 281, 284, 290, 294, 299, 306, 307, 315, 321, 323 Stool, 288, 291, 323 Stress, 5, 7, 16, 21, 31, 33, 37, 58, 156, 182, 197, 258, 263, 270, 291, 299, 304, 310, 317, 323 Stroke Volume, 262, 323 Stromal, 276, 323 Stupor, 299, 323 Subacute, 288, 320, 323 Subarachnoid, 279, 282, 324 Subclinical, 35, 79, 288, 319, 324 Subcutaneous, 189, 252, 275, 324 Subiculum, 284, 324 Submandibular, 123, 205, 324 Subspecies, 322, 324 Substance P, 296, 319, 324 Substrate, 27, 324 Succinylcholine, 74, 104, 324 Suction, 159, 168, 180, 324 Sufentanil, 117, 324 Sumatriptan, 188, 324 Superior Cervical Ganglion, 59, 324 Superoxide, 33, 58, 324 Superoxide Dismutase, 58, 324 Supine, 180, 324 Supine Position, 180, 324 Supplementation, 122, 324 Support group, 240, 324 Suppression, 25, 44, 189, 324 Supraspinal, 65, 324 Sympathetic Nervous System, 22, 58, 89, 179, 255, 257, 324, 325 Sympathomimetic, 274, 277, 301, 325 Symphysis, 265, 312, 325 Symptomatic, 43, 255, 325 Synapses, 19, 265, 293, 300, 301, 325 Synapsis, 325 Synaptic, 19, 21, 59, 293, 301, 320, 325 Synaptic Transmission, 19, 301, 325 Synaptic Vesicles, 325 Synchrony, 24, 325 Syncope, 153, 183, 325 Synergistic, 170, 325 Syphilis, 205, 325 Systolic, 94, 107, 286, 325 T Tachycardia, 20, 325 Telangiectasia, 229, 325 Telecommunications, 326

348 Apnea

Telemedicine, 116, 326 Temporal, 85, 186, 253, 278, 283, 284, 295, 326 Temporal Lobe, 253, 326 Testis, 326 Testosterone, 15, 64, 326 Thalamic, 257, 326 Thalamic Diseases, 257, 326 Thalamus, 273, 292, 310, 326 Theophylline, 114, 115, 117, 124, 218, 326 Therapeutics, 33, 75, 218, 326 Thermal, 25, 144, 273, 326 Thermoregulation, 199, 326 Third Ventricle, 287, 326 Thoracic, 89, 125, 164, 199, 260, 272, 295, 309, 326, 332 Thorax, 144, 150, 251, 326, 330 Threshold, 6, 22, 136, 137, 143, 149, 162, 277, 286, 326 Thrombosis, 312, 323, 326 Thrombus, 270, 288, 291, 298, 309, 326 Thymus, 287, 294, 327 Thyroid, 327, 329 Tidal Volume, 14, 286, 327 Tin, 263, 309, 327 Tinnitus, 199, 303, 312, 327, 331 Tolerance, 32, 37, 38, 189, 251, 266, 281, 327 Tomography, 123, 327 Tonic, 22, 57, 266, 327 Tonicity, 180, 327 Tonometry, 102, 327 Tonsillitis, 205, 327 Tonsils, 6, 72, 97, 142, 182, 327 Tonus, 306, 327 Tooth Preparation, 251, 327 Torsion, 288, 327 Toxic, iv, 188, 258, 276, 301, 327 Toxicity, 274, 327 Toxicology, 226, 327 Toxins, 256, 262, 288, 327 Trachea, 14, 192, 261, 292, 307, 327, 328 Tracheostomy, 159, 168, 328 Tracheotomy, 9, 195, 204, 328 Traction, 266, 328 Tractus, 19, 328 Tranquilizing Agents, 264, 313, 328 Transcription Factors, 58, 185, 328 Transcutaneous, 7, 126, 199, 328 Transduction, 23, 320, 328 Transfection, 259, 328 Transfer Factor, 287, 328

Transfusion, 73, 125, 328 Translation, 39, 328 Transmitter, 19, 21, 251, 257, 274, 290, 295, 300, 301, 325, 328 Transplantation, 4, 266, 287, 328 Trauma, 146, 173, 203, 204, 271, 277, 299, 328 Treatment Outcome, 44, 45, 328 Tremor, 296, 328 Tricuspid Atresia, 269, 328 Tryptophan, 52, 267, 319, 329 Tubercle, 11, 329 Tuberculosis, 202, 205, 269, 329 Tuberous Sclerosis, 229, 329 Tubulin, 297, 329 Tumor marker, 259, 329 Tumor Necrosis Factor, 66, 188, 329 Tumour, 280, 329 Turbinates, 142, 203, 329 Type 2 diabetes, 6, 9, 61, 99, 132, 198, 329 Tyrosine, 59, 274, 329 U Ultrafiltration, 99, 283, 329 Unconscious, 254, 287, 329 Uremia, 4, 291, 316, 329 Urethra, 312, 329, 330 Uric, 110, 329 Urinary, 117, 152, 183, 265, 285, 287, 309, 329 Urinate, 6, 330 Urine, 6, 236, 259, 270, 273, 284, 287, 291, 299, 309, 329, 330 Uterus, 142, 265, 270, 276, 296, 304, 311, 330 Uvula, 88, 143, 235, 321, 330 V Vaccine, 252, 312, 330 Vagal, 16, 330 Vagina, 262, 265, 296, 330 Vaginitis, 262, 330 Vagus Nerve, 291, 301, 321, 330 Vascular endothelial growth factor, 38, 73, 103, 330 Vascular Headaches, 188, 330 Vascular Resistance, 258, 330 Vasoactive, 20, 70, 210, 330 Vasoconstriction, 51, 58, 212, 277, 330 Vasodilatation, 263, 330 Vasodilation, 51, 58, 255, 330 Vasodilator, 20, 67, 89, 260, 274, 330 Vector, 328, 330 Vein, 254, 257, 290, 302, 305, 318, 330

Index 349

Velopharyngeal Insufficiency, 205, 330 Venereal, 325, 330 Venous, 43, 257, 259, 312, 328, 330 Ventilation, 23, 57, 60, 103, 130, 136, 138, 139, 146, 158, 160, 163, 167, 174, 189, 193, 194, 195, 286, 330, 331 Ventilator, 295, 316, 331 Ventral, 25, 44, 57, 114, 287, 302, 309, 322, 331 Ventricle, 253, 257, 269, 284, 313, 314, 325, 328, 331 Ventricular, 20, 21, 41, 93, 94, 151, 158, 167, 205, 210, 269, 285, 325, 328, 331 Ventricular Dysfunction, 20, 93, 158, 167, 210, 331 Ventricular Function, 21, 331 Venules, 260, 296, 331 Vertebrae, 322, 331 Vertigo, 199, 303, 331 Vestibular, 199, 282, 331 Vestibule, 289, 299, 331 Vestibulocochlear Nerve, 285, 327, 331 Vestibulocochlear Nerve Diseases, 285, 327, 331 Veterinary Medicine, 225, 331 Viral, 202, 205, 281, 328, 331 Virilism, 285, 331 Virulence, 257, 327, 331

Virus, 258, 264, 280, 281, 288, 308, 328, 331 Visceral, 51, 65, 67, 258, 292, 306, 330, 332 Visceral Afferents, 258, 330, 332 Viscosity, 73, 332 Vitamin A, 289, 332 Vitreous Hemorrhage, 272, 332 Vitro, 19, 332 Vivo, 19, 28, 332 Vocal cord, 100, 281, 307, 332 Voice Disorders, 203, 204, 205, 332 W Wakefulness, 22, 31, 37, 40, 41, 49, 50, 57, 79, 87, 109, 126, 158, 167, 181, 271, 332 Weight Gain, 46, 94, 170, 198, 332 White blood cell, 255, 266, 288, 292, 294, 301, 308, 332 Whooping Cough, 307, 332 Windpipe, 276, 307, 327, 332 Withdrawal, 56, 65, 153, 184, 189, 271, 332 Womb, 330, 332 Wound Healing, 263, 332 X Xenograft, 255, 332 Xerostomia, 5, 8, 332 X-ray, 268, 279, 302, 314, 318, 332 Y Yeasts, 262, 279, 307, 332 Yohimbine, 114, 332

350 Apnea

Index 351

352 Apnea

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