Traumatic Brain Injury - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

TRAUMATIC BRAIN INJURY A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCE...

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

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

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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 2004 by ICON Group International, Inc. Copyright 2004 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1

Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Traumatic Brain Injury: 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: 0-597-84663-4 1. Traumatic Brain Injury-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 traumatic brain injury. 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 TRAUMATIC BRAIN INJURY ...................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Traumatic Brain Injury ................................................................ 7 E-Journals: PubMed Central ....................................................................................................... 64 The National Library of Medicine: PubMed ................................................................................ 65 CHAPTER 2. NUTRITION AND TRAUMATIC BRAIN INJURY .......................................................... 115 Overview.................................................................................................................................... 115 Finding Nutrition Studies on Traumatic Brain Injury ............................................................. 115 Federal Resources on Nutrition ................................................................................................. 122 Additional Web Resources ......................................................................................................... 123 CHAPTER 3. ALTERNATIVE MEDICINE AND TRAUMATIC BRAIN INJURY .................................... 125 Overview.................................................................................................................................... 125 National Center for Complementary and Alternative Medicine................................................ 125 Additional Web Resources ......................................................................................................... 131 General References ..................................................................................................................... 133 CHAPTER 4. DISSERTATIONS ON TRAUMATIC BRAIN INJURY ...................................................... 135 Overview.................................................................................................................................... 135 Dissertations on Traumatic Brain Injury .................................................................................. 135 Keeping Current ........................................................................................................................ 142 CHAPTER 5. PATENTS ON TRAUMATIC BRAIN INJURY ................................................................. 143 Overview.................................................................................................................................... 143 Patents on Traumatic Brain Injury ........................................................................................... 143 Patent Applications on Traumatic Brain Injury ....................................................................... 165 Keeping Current ........................................................................................................................ 189 CHAPTER 6. BOOKS ON TRAUMATIC BRAIN INJURY .................................................................... 191 Overview.................................................................................................................................... 191 Book Summaries: Federal Agencies............................................................................................ 191 Book Summaries: Online Booksellers......................................................................................... 193 Chapters on Traumatic Brain Injury ......................................................................................... 204 Directories.................................................................................................................................. 206 CHAPTER 7. MULTIMEDIA ON TRAUMATIC BRAIN INJURY .......................................................... 209 Overview.................................................................................................................................... 209 Video Recordings ....................................................................................................................... 209 CHAPTER 8. PERIODICALS AND NEWS ON TRAUMATIC BRAIN INJURY ....................................... 211 Overview.................................................................................................................................... 211 News Services and Press Releases.............................................................................................. 211 Newsletter Articles .................................................................................................................... 215 Academic Periodicals covering Traumatic Brain Injury............................................................ 215 CHAPTER 9. RESEARCHING MEDICATIONS .................................................................................. 217 Overview.................................................................................................................................... 217 U.S. Pharmacopeia..................................................................................................................... 217 Commercial Databases ............................................................................................................... 218 Researching Orphan Drugs ....................................................................................................... 218 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 223 Overview.................................................................................................................................... 223 NIH Guidelines.......................................................................................................................... 223 NIH Databases........................................................................................................................... 225 Other Commercial Databases..................................................................................................... 227 APPENDIX B. PATIENT RESOURCES ............................................................................................... 229

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Overview.................................................................................................................................... 229 Patient Guideline Sources.......................................................................................................... 229 Associations and Traumatic Brain Injury ................................................................................. 273 Finding Associations.................................................................................................................. 273 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 275 Overview.................................................................................................................................... 275 Preparation................................................................................................................................. 275 Finding a Local Medical Library................................................................................................ 275 Medical Libraries in the U.S. and Canada ................................................................................. 275 ONLINE GLOSSARIES................................................................................................................ 281 Online Dictionary Directories ................................................................................................... 283 TRAUMATIC BRAIN INJURY DICTIONARY ....................................................................... 285 INDEX .............................................................................................................................................. 375

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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 traumatic brain injury is indexed in search engines, such as www.google.com or others, a non-systematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to know as much as possible about traumatic brain injury, 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 traumatic brain injury, 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 traumatic brain injury. 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 traumatic brain injury, 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 traumatic brain injury. 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 TRAUMATIC BRAIN INJURY Overview In this chapter, we will show you how to locate peer-reviewed references and studies on traumatic brain injury.

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

Dental Hygiene Treatment for a Traumatic Brain Injury Patient Source: Journal of Practical Hygiene. 10(1): 27-31. January-February 2001. Contact: Available from Montage Media Corporation. 1000 Wyckoff Avenue, Mahwah, NJ 07430-3164. (201) 891-3200. Summary: A traumatic brain injury (TBI) can be either a closed head injury or a penetration injury. This article discusses closed head trauma and the possible emotional side effects and potential cognitive effects. Although the effects of a TBI can be varied in their type and severity, the authors emphasize the importance of dental hygienists understanding the potential influence of a TBI on a patient's emotional and physical well being. In addition, the authors review the literature that addresses the dental

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Traumatic Brain Injury

hygiene practices needed to improve or maintain the oral and overall health of traumatic brain injury patients. The authors present a case report to demonstrate the dental hygiene management of a patient who experienced a traumatic brain injury due to an automobile accident. One way the clinician can aid a patient with memory loss is through the use of a laminated chart that should show pictures of brushing, flossing, and use of the recommended oral rinse. Diet therapy can also be helpful, especially to counter the effects of medications on dry mouth (xerostomia). The authors also consider the importance of including the patient's caregiver when providing care or instructions to the patient. The dental hygienist should address the patient first and then repeat the instructions for the caregiver. TBI patients need additional time to develop responses to questions and stimuli, and require patience and understanding from health care professionals. 5 figures. 21 references. •

Traumatic Brain Injury in Adolescence: Assessment and Reintegration Source: Seminars in Speech and Language. 16(1): 32-45. February 1995. Summary: For many educators and school-based clinicians, traumatic brain injury (TBI) is a new and possibly confusing disability category. In this article, the authors explain the usefulness of this category and outline several major themes in communicationrelated assessment and intervention associated with this population. The authors emphasize the cognitive, behavioral, and psychosocial dimensions of disability because they often dominate the outcome picture after TBI, especially for adolescents, and because they are easily misinterpreted. The discussion of intervention themes is directed primarily at the important goal of successfully including students with TBI in their community schools despite possibly significant cognitive and psychosocial challenges. The authors also emphasize the importance of an interdisciplinary approach as the best way to deliver services to this population. 2 tables. 74 references. (AA-M).

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Supporting Families After Head Injury: Implications for the Speech-Language Pathologist Source: Seminars in Speech and Language. 14(1): 44-60. February 1993. Summary: People with brain injury face many paradoxical forces that can interfere with community life and are subject to expectations that are not compatible with the reality of living with a brain injury. This article examines how speech-language pathologists can help people live with traumatic brain injury (TBI). The author describes how the community responds to people with TBI, presents competing models for understanding disability, and discusses how best to understand TBI within these models. Models covered include the developmental disabilities model, the medical model, and the independent living model. The author also discusses family systems and how family members assimilate the experience of brain injury in their lives. The author urges speech language clinicians to support families from the perspective of family strengths rather than that of a dysfunctional family, and has advocated community-based support and services rather than institutional care. When a member of a family becomes brain injured, any sense of control and predictability is gone. For families to regain the mastery and predictability they need, a strong social support network is required. 32 references. (AA-M).

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Treatment Efficacy: Cognitive-Communicative Disorders Resulting from Traumatic Brain Injury in Adults Source: Journal of Speech and Hearing Research (JSHR). 39(5): S5-S17. October 1996.

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Summary: This article contends that there is both scientific and clinical evidence that individuals with cognitive-communicative disorders resulting from traumatic brain injury (TBI) benefit from the services of speech-language pathologists. Cognitivecommunication impairments are the result of deficits in linguistic and nonlinguistic cognitive functions. The role of the speech-language pathologist includes assessment of all aspects of communication, as well as the communicative implications of cognitive deficits, and swallowing. Speech-language pathologists also provide treatment planning and programming, as determined by the individual's stage of recovery; client and family training and counseling; and interdisciplinary consultation. The author illustrates the effectiveness of speech and language intervention by scientific and clinical evidence from group-treatment and single-subject studies as well as case studies. 5 tables. 92 references. (AA-M). •

Social-Environmental Approach to Communication and Behavior after Traumatic Brain Injury Source: Seminars in Speech and Language. 14(1): 76-87. February 1993. Summary: This article describes the rationale for a social-environmental approach to communication and behavior rehabilitation after severe brain injury. The authors present a perspective that involves a blending of speech-language pathology and behavioral psychology services in a holistic and contextual approach to the interaction of communicative and behavioral challenges. The authors stress the importance of everyday people as primary agents of change and recovery. Training procedures, which have been found useful in creating a positive communication culture for rehabilitation, are outlined. Procedures described include in-service training, coaching, and peer training. 1 figures. 3 tables. 42 references. (AA-M).

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Educational Considerations in Traumatic Brain Injury: The Role of the SpeechLanguage Pathologist Source: Language, Speech, and Hearing Services in Schools. Volume 24: 67-75. April 1993. Summary: This article describes the role of speech-language pathologists in service provision to children and youth with traumatic brain injury (TBI). The author notes that the speech pathologist's role in educational settings has become blurred with that of numerous disciplines. The author considers the federal legislation, PL 101-476 (IDEA), which designates a separate educational disability category for brain injury. The author discusses associated variables in TBI, including severity and outcome, cognitive defects, speech and language profiles, assessment, and diagnostic treatment. The article concludes with a section considering the use of the speech language pathologist as the case manager for these children. The professional preparation of the speech language pathologist provides a sound foundation for working with the cognitive, linguistic, and motor speech problems that result from neurological insult following TBI and that can affect educational reintegration. In addition, case management requires knowledge of relevant resources and awareness of medical and educational policies and legislature mandates. 2 tables. 54 references. (AA-M).

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Traumatic Brain Injury and Severe Expressive Communication Impairment: The Role of Augmentative Communication Source: Seminars in Speech and Language. 14(1): 61-73. February 1993.

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Summary: This article provides information on the use of augmentative and alternative communication (AAC) in treating individuals with traumatic brain injury (TBI) and resulting severe expressive communication disorders. The author presents information on a cognitive framework for assessment and intervention, phases of recovery following TBI, application of augmentative communication across phases of recovery, the use of multiple techniques, interdisciplinary involvement, partner advocacy and involvement, and short-and long-term intervention goals. The author uses case examples to illustrate the concepts presented. The author concludes that, whether the challenge is to establish basic communication or to determine how sophisticated communication technology might improve an individual's chances for educational or vocational re-entry, it is clear that augmentative communication has a central place in the rehabilitation of many individuals with TBI. 4 tables. 18 references. (AA-M). •

Intensive Voice Treatment and Respiration Treatment for Hypokinetic-Spastic Dysarthria After Traumatic Brain Injury Source: American Journal of Speech-Language Pathology. 10(1): 51-64. February 2001. Contact: Available from American Speech-Language-Hearing Association (ASHA). Subscription Sales Coordinator, 10801 Rockville Pike, Rockville, MD 20852-3279. (888) 498-6699. Fax (301) 897-7358. Website: www.asha.org. Summary: This article reports on a study in which the short term efficacy of the Lee Silverman Voice Treatment (LSVT) and the short and long term efficacy of LSVT exercises combined with respiration treatment and physical therapy (Combination Treatment) were examined in a young man. The patient was diagnosed with mixed hypokinetic spastic dysarthria (a motor speech impairment) 20 months after sustaining a traumatic brain injury (TBI). The efficacy of the LSVT, an intensive 4 week program that focuses on increased vocal effort, is well documented for idiopathic Parkinson's disease. The authors note that their account is the first known published use of LSVT with TBI. Breathing and speech function were assessed by spirometry, respiratory kinematics, intelligibility, and other selected acoustic and auditory perceptual measures. Improvements generally were minor and inconsistent after LSVT, although sound pressure level (SPL) and loudness increased notably. After an additional 6 weeks of intensive Combination Treatment, the patient demonstrated gains for resting and speech breathing. In addition, SPL increased further and sentence intelligibility improved substantially. The gains were maintained to varying degrees after 10 weekly sessions of Combination Treatment. Although several measures returned to baseline 3 months after treatment ceased, some improvements in resting and speech breathing remained. Most importantly, improvements in vocal SPL and sentence intelligibility persisted in this patient. On the basis of these results, Combination Treatment, including LSVT, respiration treatment, and physical therapy, is recommended for individuals with mixed hypokinetic spastic dysarthria and upper body hypertonicity regardless of etiology (cause). 3 figures. 4 tables. 26 references.

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Acoustic Characteristics of Voice After Severe Traumatic Brain Injury Source: Laryngoscope. 110(7): 1157-1161. July 2000. Contact: Available from Lippincott Williams and Wilkins. 12107 Insurance Way, Hagerstown, MD 21740. (800) 638-3030 or (301) 714-2300. Fax (301) 824-7390. Summary: This article reports on a study undertaken to describe the acoustic characteristics of voice in individuals with motor speech disorders after traumatic brain injury (TBI). The prospective study of 100 individuals with TBI was based on

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consecutive referrals for motor speech evaluations. Subjects were audiotape recorded while producing sustained vowels and single word and sentence intelligibility tests. Laryngeal airway resistance was estimated, and voice quality was rated perceptually. Results indicated that none of the subjects showed vocal parameters within normal limits. The most frequently occurring abnormal parameter across subjects was amplitude perturbation, followed by voice turbulence index. Twenty three percent of subjects evidenced deviation in all five parameters measured. The perceptual ratings of breathiness were significantly correlated with both the amplitude perturbation quotient and the noise to harmonics ratio. The author concludes that vocal quality deviation is common in motor speech disorders after TBI and may affect intelligibility. 2 figures. 26 references. •

Communication Outcome Following Traumatic Brain Injury Source: Seminars in Speech and Language. 13(4): 239-251. November 1992. Summary: This article summarizes the communication disorders associated with traumatic brain injury (TBI). Topics covered include aphasic language disorders; nonaphasic language disorders; prefrontal injury; executive system dysfunction and communication; cognitive factors including attention, awareness, perception, memory, learning, organization, and social cognition; and motor speech outcome. The author stresses that an understanding of the interesting features of prefrontal injury yields profound insights for the valid assessment and treatment of individuals with TBI. 1 figure. 63 references.

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'Potential' Contributions of Cognitive Behavior Modification to the Rehabilitation of Individuals with Traumatic Brain Injury Source: Seminars in Speech and Language. 14(1): 18-31. 1993. Summary: This article, directed toward health professionals, describes cognitive behavior modification (CBM) and its potential application for people having traumatic brain injury. The article provides information on self-instructional training, stress inoculation training, and cognitive restructuring procedures. It presents a therapeutic framework and basis for further dialogue between CBM theorists and practitioners, including speech-language pathologists involved in client rehabilitation. References are included.

Federally Funded Research on Traumatic Brain Injury The U.S. Government supports a variety of research studies relating to traumatic brain injury. 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.

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

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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 traumatic brain injury. 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 traumatic brain injury. The following is typical of the type of information found when searching the CRISP database for traumatic brain injury: •

Project Title: ADENOSINE AND TRAUMATIC BRAIN INJURY Principal Investigator & Institution: Kochanek, Patrick M.; Associate Professor; Critical Care Medicine; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 02-AUG-1999; Project End 31-JUL-2003 Summary: Traumatic brain injury (TBI) is an enormous public heath problem; however, targeted therapies are lacking. After severe TBI, ischemia and energy failure frequently occur. Adenosine is a purine nucleotide that acts as a powerful endogenous neuroprotectant during ischemia-induced energy failure by decreasing neuronal metabolism and increasing cerebral blood flow (CBF), among other mechanisms. These effects are mediated through interaction of adenosine with specific receptors. The synergistic effects of increasing CBF and decreasing metabolism suggest an important neuroprotectant role for adenosine after TBI, particularly during secondary insults. Further augmenting the effects of adenosine in brain may reduce neuronal damage. Two strategies to achieve this are particularly relevant to TBI and this application, namely, 1) the inhibition of adenosine metabolism or 2) the local administration of adenosine analogs. Defining four Specific Aims, we will use an established rat model of TBI and applying cerebral microdialysis, contemporary MRI tools, functional outcome testing, and histology, we will first determine the magnitude of the adenosine response (brain interstital levels of adenosine and purine degradation products) to experimental TBI. We will then examine effects of these two defined strategies of augmenting adenosine effects both on key mechanisms of secondary damage (excitotoxicity [brain interstitial levels of glutamate, CBF by perfusion MRI, and Ca++ accumulation in brain by Mn++contrast-enhanced MRI) and both functional and histopathological outcome. Finally, in a fifth Specific Aim, we will bridge bench to bedside by using cerebral microdialysis methods to define the participation of adenosine (and its relationship to CBF and excitotoxicity) after severe TBI in humans, during the application of contemporary therapeutic interventions (CSF drainage, mannitol, hyperventilation, and barbiturates) in the treatment of intracranial hypertension. If successful, these studies will set the stage for a clinical trial, and provide important mechanistic information on the role of adenosine after TBI in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ADRENAL INSUFFICIENCY AFTER MODERATE&SEVERE HEAD INJURY Principal Investigator & Institution: Cohan, Pejman E.; Harbor-Ucla Research & Educ Inst 1124 W Carson St Torrance, Ca 905022052 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007

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Summary: (provided by applicant): Pituitary function is rarely considered in the care of patients with traumatic brain injury (TBI). Yet, TBI poses significant risk to pituitary function given the gland's encasement within the sella, its delicate infundibularhypothalamic structures and vulnerable vascular supply. Autopsy studies of fatal head injury victims confirm that up to one-third of patients sustain acute pituitary necrosis. The investigators and other investigators have documented chronic pituitary failure in long-term follow up studies of TBI subjects. The purpose of this study is to define acute post-traumatic changes in the hypothalamic-pituitary adrenocortical axis given that this hormonal axis is essential for survival, particularly in times of critical illness such as head injury. The major hypotheses to be tested in this study are: 1) a significant proportion of TBI victims suffer from unrecognized ASAI; 2) that ASAI results primarily from hypothalamic-pituitary hypoperfusion; 3) that the consequences of ASAI are systemic hypotension, increased vasopressor requirements and increased levels of serum and cerebrospinal fluid (CSF) proinflammatory cytokines; and 4) that treatment of individuals with ASAI with acute stress doses of glucocorticoids will improve blood pressure control, decrease CSF cytokine levels, shorten intensive care unit stay and improve neurological outcome. To test these hypotheses, they will first compare serial serum cortisol and ACTH levels over the first 10 days after injury in TBI versus matched non-TBI multiple trauma subjects to define ASAI. Next, TBI patients found to have inappropriately low cortisol levels that met criteria of ASAI, will be randomized to 48 hours of placebo or hydrocortisone therapy and changes in hemodynamics, cytokine levels, and neurological outcome will be measured. Pituitary/hypothalamic magnetic resonance imagings (MRIs) will be performed to assess for acute structural lesions and chronic pituitary volumetric changes. By diagnosing and treating acute traumatic neuroendocrine deficiency, this study may lead to dramatically improved management and neurological outcome of many future TBI patients. This proposal will help the candidate develop the theoretical and practical research skills necessary for an independent career in clinical investigation. The project will be done at two scientifically rich institutions supported by two GCRCs under the guidance of two experienced mentors from two different subspecialties appropriate for the study and the candidate's career development. Formal research instruction via the K30 Graduate Program at UCLA and courses at Harbor UCLA will complement the candidate's firm background in clinical medicine and endocrinology and enable him to successfully pursue a career as a clinical investigator in the field of neuroendocrinology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: AN FMRI STUDY OF EXECUTIVE FUNCTIONING AFTER TBI Principal Investigator & Institution: Levin, Harvey S.; Professor/Director of Research; Phys Med and Rehabilitation; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-JUL-2006 Summary: (provided by applicant) Executive functions (EFs) are cognitive control processes that include flexibility in problem solving, planning, allocation of attention, maintenance and manipulation of information over time, and self-regulation. EFs, which deploy specific cognitive skills such as declarative memory and other domains such as perceptuomotor skills, are mediated by prefrontal cortex and its circuitry. EFs are frequently impaired after traumatic brain injury (TBI), thus contributing to disability and reduced quality of life. Working memory and inhibition are fundamental processes of EFs which have been associated with prefrontal cortex and its network. Although the prefrontal region is vulnerable to injury by acceleration/deceleration and blunt trauma,

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structural brain imaging is limited in understanding the neurobiology of EF deficits after TBI. Using functional magnetic resonance imaging (fMRI), the Aims 9 of this 3 center project are to (1) Investigate whether the extent of cortical activation during working memory (N-back for faces) and inhibition (left-right incompatibility of arrows) tasks in adults 3 months following moderate to severe TBI differs from that of adults who have sustained extracranial injury; (2) Examine longitudinal changes in activation of prefrontal and related cortical regions during performance of working memory and inhibition tasks in TBI patients reimaged at I year postinjury; (3) Investigate the relationship between patterns of brain activation during working memory and inhibition tasks at 3 months and 1 year postinjury and performance on laboratory, clinical, and everyday measures of EF; (4) In an ongoing study of a separate cohort of moderate to severe TBI patients, evaluate the effects of methylphenidate (MPH) taken for 1 month on prefrontal activation during performance of working memory and inhibition tasks and the associated changes in performance on EF measures. Moderate to severe TBI patients (total n= 180) and general trauma patients (total n=60) will be recruited from the neurosurgery and surgery services at 3 centers. Aims 1-3 will be addressed by fMRI and EF assessment at 3 months and 1 year postinjury. Aim 4 will involve fMRI and EF assessment of TBI patients with working memory deficit who are treated for 28 days with MPH 15 in- bid beginning between 3 and 12 months postinjury. Patients studied for Aim 4 will undergo fMRI and EF assessment before beginning MPH and 1 hour after their final dose of MPH. Laboratory EF measures include dual task performance, subject ordered pointing, N-back letters task, selective learning, and risk taking; the revised Neurobehavioral Rating Scale provides clinical ratings of EFs; and assessment of EFs in everyday activities will include measures of dysexecutive functioning and planning. Analyses will test TBI-related alterations in brain activation at 3 months postinjury, changes on reimaging at 1 year, relationship to EFs, and MPH effects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: AN ORGANOTYPIC MODEL OF TRAUMATIC BRAIN INJURY Principal Investigator & Institution: Bottlang, Michael; Emanuel Hospital and Health Center Portland, or 97208 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2005 Summary: The past decade has witnessed intense scientific activity to investigate molecular mechanisms of traumatic brain injury, driven by overwhelming evidence that neuropotection by pharmacological inhibition of apoptosis has the potential to dramatically reduce the effects of brain trauma. Key requisite for the systematic investigation of neuroprotective agents is an accurately characterized, clinically relevant in vitro brain injury model. Despite this obvious need, the ability to deliver such defined, realistic trauma to specimens in vitrolags far behind the sophistication of molecular and biochemical assays used to measure the response. In a collaborative effort between neurobiologists and bioengineers, we therefore developed an in vitrobrain injury model which subjects organotypic brain cultures to angular acceleration-induced shear injury. In this model, organotypic brain cultures realistically model the in vivoapparent heterogeneous cell population in a three-dimensional cellular matrix, while angular acceleration-induced shear strain delivers a scalable, defined, and clinically relevant mechanical insult. We hypothesize that our acceleration model of organotypic brain cultures can realistically reproduce traumatic brain injury, where the delivered shear strain magnitude can be quantified on a cellular level. Exercising our model, we will be able to determine cell type specific injury vulnerability, and to

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determine if caspase-8 and caspase-9 affect cell death following brain trauma. We propose to complete a formal experimental characterization of our novel brain injury system, including assessment of the delivered angular acceleration magnitude and determination of the constitutive properties of the organotypic specimen (Aim 1). The resulting experimental source data will be directly applicable to formulate a realistic analytical model that allows computational simulation of the shear injury throughout the brain specimen for any point in time during the primary mechanical insult (Aim 2). Based on and concomitant to this rigorous system characterization, we will exercise the brain injury model to establish a dose/response history (Aim 3), and we will delineate the effects of hypoxic brain injury (Aim 4), secondary to the mechanical insult. Finally, we will employ our arganotypic trauma model to determine the neuroprotective potential of caspase-8 and caspase-9 (Aim 5). Upon successful completion, the results of this integrative research approach will yield a well-characterized, scalable, reproducible and clinically relevant brain injury model. Considering the vast interest in therapeutic interventions now under development aimed at inhibiting the cascade of secondary effects of primarily mechanical brain injuries, our organotypic trauma model will directly address the rapidly increasing demand for a well characterized, experimental system to deliver a clinically relevant traumatic insult - and may prove crucial for the discovery of caspase-based neuroprotective mechanisms. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ANALYSIS OF MARROW STROMAL CELL INTERACTION WITH TISSUE Principal Investigator & Institution: Zhang, Zheng G.; Senior Staff; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2003; Project Start 15-JUL-2003; Project End 31-MAY-2008 Summary: Stroke and traumatic brain injury are major causes of morbidity and disability and functional recovery is slow and uncertain. Our preliminary data demonstrate that intravenously transplanted bone marrow stromal cells (MSCs) migrate to the stroked and injured brain tissue and improve functional recovery, This application is concerned with elucidating the cellular and molecular mechanisms responsible for the beneficial effect of MSC therapy on stroke and traumatic brain injury. The major hypothesis to be tested is that the MSCs delivered to the brain after stroke and traumatic brain injury enhance angiogenesis, promote axonal and dendritic sprouting and synapse formation, reduce cell death in the boundary regions of injured brain, and promote neurogenesis in the subventricular zone and dentate gyrus and thereby reduce neurological deficits, in addition, we propose to test the hypothesis that therapeutic benefit derives from MSC-induced increase in brain of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and brain-derived neurotrophic factor (BDNF). This hypothesis will be tested by blocking receptors and using gone knock-out mice. Specifically, by blocking VEGF receptor 2, we will examine the effect of VEGF on MSC-enhanced angiogenesis. Using bFGF-/- and BDNF-/-mice, we will examine the effects of bFGF and BDNF on MSC-induced axonal and dendritic sprouting and synapse formation and neurogenesis. Angiogenesis, neurogenesis and axonal and dendritic sprouting and synapse formation will be measured using Laser Scanning Confocal Microscopy, and a novel software program for three dimensional image analysis. We believe that these are unique and fresh approaches that may provide fundamental insights into the cellular and molecular mechanisms underlying the therapeutic benefit provided by MSC cellular therapy of stroke and traumatic brain injury.

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

Project Title: BIOMARKER OF NEUROPROTECTANT EFFICACY Principal Investigator & Institution: Gabbita, Somasundar P.; Phase 2 Discovery, Inc. 3130 Highland Ave, 3Rd Fl Cincinnati, Oh 45219 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JAN-2003 Summary: (provided by applicant): The objective of this Phase I feasibility study is to develop a sensitive biomarker for quantifying neuroprotectant drug efficacy in a rat model of traumatic brain injury (TBI). Currently, no widely accepted biochemical marker that quantifies neuronal injury in rat TBI models is available. We have previously shown that during axonal degeneration in humans, the brain cytoskeletal protein MAP-tau is cleaved. Our laboratory has developed a sensitive ELISA that specifically measures cleaved MAP-tau (C-tau) in human CSF following head injury. Using this ELISA, we have shown that brain C-tau levels increase in rats after sustaining cortical impact-induced TBI. By measuring lesion volumes, Scheff et al have previously demonstrated that cyclosporin A administration following TBI significantly ameliorates cortical damage in the cortical impact rat model. We hypothesize that C-tau is a reliable biomarker of TBI-induced neuronal injury in rats. We will test this hypothesis by determining if C-tau levels demonstrate a time-dependent increase after TBI and if a known neuroprotectant intervention, cyclosporin A, exerts expected effects on C-tau levels. Our Specific Aims are: Specific Aim 1: Determine whether TBI results in a timedependent increase in brain levels of C-tau. C-tau levels will be quantified by ELISA in TBI-affected and control brain regions and also in sham operated animals. Specific Aim 2: Determine if C-tau levels reliably quantify the effect of a known neuroprotectant intervention on TBI. The neuroprotective effect of cyclosporin A will be examined by administering either vehicle or cyclosporin A. C-tau levels will be quantified by ELISA at the time of maximum TBI-induced C-tau elevation determined in Specific Aim 1. Ctau levels will be compared as a function of neuroprotectant treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CASPASE MECHANISMS AFTER BRAIN INJURY Principal Investigator & Institution: Moskowitz, Michael A.; Professor; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 15-DEC-1997; Project End 31-DEC-2006 Summary: Adapted from applicant's abstract): Stroke and brain injury are major causes of morbidity and mortality and significant economic loss. This competitive renewal application will explore novel hypotheses relating to regulation of death receptors as mediators of cell death in vivo and in vitro. Preliminary evidence suggests that a Death Inducing Signaling Complex (DISC) assembles after acute brain injury and initiates caspase activation leading to cell death. Five aims are proposed to contrast mechanisms relating to the death receptor Fas, death effector proteins, and initiator caspase-8 and -10 in vivo after acute brain injury (cerebral ischemia and brain trauma). In experimental models, caspase-8 cleavage and DISC assembly was significantly greater in trauma than ischemia, suggesting differences in cell death mechanisms between acute brain injuries. To explain these differences, we propose a novel hypothesis that TYPE I (mitochondriaindependent) may be more typical of head trauma and TYPE II (mitochondriadependent) cell death may predominate in ischemia, and this hypothesis will be tested in Bid-/- null mice. To dissect mechanisms regulating DISC assembly, we propose in vitro studies using enriched cortical neurons and oxygen-glucose deprivation (OGD).

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Our preliminary data indicate that adding FasL kills neurons during OGD, and cell death after OGD is reduced by caspase inhibitors. We propose to determine whether both OGD and FasL cell death can be regulated by c-FLIP, an inhibitor of caspase-8 activation, using viral vectors to overexpress the c-FLIP gene. In vitro studies will explore regulation of FasL expression by determining whether inhibition of Forkhead transcription factor (FKHRLI), which promotes FasL synthesis, reduces OGD-mediated neuronal cell death. We also propose to establish the functional relevance of Fas/FasL signaling in vivo using Fas-/- mice, antisense treatment, gld mice and overexpression of c-FLIP using HSV-I amplicon viral transfer. Finally, we will expand upon preliminary data detecting DISC assembly in human brain following acute injury and thereby validate the importance of cell surface death receptors in acute injury. Together these experiments will explore death receptor-mediated acute cell killing within brain in order to identify mechanisms and potential targets of ischemic and traumatic brain injury. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CASPASE MEDIATED NEURONAL DEATH AFTER HEAD INJURY Principal Investigator & Institution: Clark, Robert S.; Associate Professor; Anesthesiology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 01-FEB-1999; Project End 31-JAN-2003 Summary: Caspase activation is the first committed step in the programmed-cell death cascade, a tightly regulated sequence of cellular and molecular events that systematically leads to the death of a cell. Increasing evidence suggests that activation of caspases produces secondary neuronal death after traumatic brain injury in experimental models. Importantly, pharmacologic and molecular inhibitors of the caspases attenuate programmed cell-death after cerebral ischemia and traumatic brain injury in rodents, although reports are limited. Our hypothesis is that activation of caspases after traumatic brain injury contributes to neuronal death and that inhibiting induction and/or activity of caspases reduces secondary neuropathologic injury after traumatic brain injury. Specific aims to address this hypothesis will: 1) characterize the temporal, regional, cellular, and subcellular expression and activity of Caspase-3 using a rat model that mimics severe human traumatic brain injury, 2) examine the upstream regulation the upstream regulation of caspases by cytosolic cytochrome c and nitric oxide after severe traumatic brain injury in rats and mice, 3) test the effects of several pharmacologic caspase inhibitors on neuropathologic and functional outcome after severe traumatic brain injury in rats, 4) examine the expression of other caspases (Caspases-2 and -9) after severe traumatic brain injury in rats, and 5) examine the expression of currently identified caspase (Caspases -2 -9) after severe traumatic brain injury in rats, and 5) examine the expression of currently identified caspases (Caspases 1-10) after severe traumatic brain injury in humans. Traumatic brain injury is a major cause of mortality and morbidity in adults and children in the United States. Secondary brain injury contributes to mortality and morbidity in adults and children in the United States. Secondary rain injury contributes to mortality and morbidity and currently only few, non-specific therapies are available. Caspase-mediated programmed-cell death may contribute to secondary neuronal death after traumatic brain injury in experimental models and in humans as well. Pharmacologic treatment strategies aimed at reducing caspase induction and/or activation to subsequently reduce secondary neuronal death will be tested in models of traumatic brain injury in vivo. If caspase inhibitors reduce programmed-cell death and improve neurologic outcome after severe traumatic brain

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injury in vivo, a novel, clinically relevant treatment strategy for victims of severe head injury will be available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHILD AND FAMILY SEQUELAE OF PRESCHOOL BRAIN INJURY Principal Investigator & Institution: Wade, Shari L.; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, Oh 452293039 Timing: Fiscal Year 2002; Project Start 10-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): Traumatic brain injury (TBI) in younger children results in more severe and persistent sequelae than TBI in older children, affecting emerging skills most. Yet, little is known regarding the effects of early TBI on the family or the factors that facilitate or hinder recovery among children in this age group. Research suggests that family and social factors play an important role in determining longer-term outcome following TBI in school-aged children. The current investigation uses a prospective cohort design to examine family adaptation following TBI in young children and the relationship between the social environment and child recovery over time. Children aged 3 to 6 with moderate to severe TBI will be compared to a matched group of children hospitalized for orthopedic injuries not involving the CNS. Children in both groups will be assessed shortly after the injury and at 6, 12, and 24 months post injury. Child outcomes of interest include emerging skills in the domains of language, social competence, and executive functions that are likely to have important implications for later functioning. Family outcomes include injury-related burden, caregiver and family functioning, and parent-child interactions. We hypothesize that families of young children with TEI will exhibit more burden and caregiver distress, poorer family functioning, and higher levels of directiveness and restrictiveness in interactions with their children than families of children with orthopedic injuries. Further, we hypothesize that both the pre-injury social environment and changes in the family brought about by the injury will be related to the child's recovery, and that these associations will be moderated by injury severity, such that the environment has a stronger influence among children with more severe TBI. We anticipate that certain aspects of the environment (e.g., maternal maintaining behaviors) will accelerate recovery, whereas others (e.g., maternal directiveness) will retard growth following TBI. Understanding the relevance of the environment to the child's recovery following TBI will allow us to develop interventions to improve outcomes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CLINICAL TRIAL DESIGN/ANALYSIS IN TRAUMATIC BRAIN INJURY Principal Investigator & Institution: Maas, Andrew I.; Erasmus University of Rotterdam Box 1738, 3000 Dr Rotterdam Rotterdam, Timing: Fiscal Year 2003; Project Start 15-FEB-2003; Project End 31-JAN-2006 Summary: (provided by the applicant): Traumatic brain injury (TBI) constitutes a major health and socio-economic problem throughout the world, accounting for a third of trauma deaths and for a much larger proportion of life-long disability after trauma. Despite enthusiasm generated from positive pre-clinical investigations, and of phase II trials on new therapies for reducing secondary brain damage and improving outcome, the results of phase III trials have been extremely disappointing, none of them showing convincing evidence of efficacy in the overall population of TBI. Problems in clinical trial design and analysis, specific to the field of TBI, have contributed to this failure.

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Methodologic challenges are related to the heterogeneity of the population, outcome assessment, detection of treatment effects, the use of surrogate markers and interim analysis. Addressing these problems requires a multidisciplinary effort involving expertise from the fields of clinical research, biostatistics and epidemiology. This effort is realized in the proposed study, organized as an international collaboration, based on extensive analysis of data available from studies (n=3) and trials (n=8) in TBI, encompassing approximately 10,000 patients. The efficiency of mechanistic and/or prognostic targeting, as well as covariate adjustment for dealing with heterogeneity, will be investigated (spec. aim 1), influence of outcome distribution and observer variation on statistical power, differentiated analysis of outcome according to prognostic risk (spec. aim 2), and development/validation of prognostic models with conventional statistical approaches, as well as with approaches new to the field of TBI (spec. aim 3). Additional design issues, considered relevant to TBI trials, focusing on recruitment, time-windows, and sequential design are addressed (spec. aim 4). The insight obtained from these investigations will lead to informed recommendations for the design and analysis of future clinical trials. Results may also be relevant to trials in other fields of medicine, in which similar problems have been recognized, such as stroke, sepsis and ARDS. The global aim is to optimize chances for demonstrating benefit of an effective new therapy or therapeutic agent in the field of TBI. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COGNITIVE DYSFUNCTION AFTER TBI: ROLE OF ALPHA7 NACHRS Principal Investigator & Institution: Pauly, James R.; Assistant Professor; Pharmacol & Exper Therapeutics; University of Kentucky 109 Kinkead Hall Lexington, Ky 40506 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2006 Summary: Trauma to the CNS initiates acute and secondary cascades of biochemical and metabolic changes often results in a state of persistent neurological dysfunction. Understanding the neurochemical alterations that occur following damage to the CNS is critical for the development of therapeutic strategies that can prevent and/or remediate the detrimental effects of trauma. The neurobiological basis for the protracted memory deficit that commonly occurs following traumatic brain injury (TBI) is not clearly understood although a number of studies have suggested that deficits in the CNS cholinergic system play a prominent role. However, most of the previous studies have focused on muscarinic, rather than nicotinic cholinergic receptor mechanisms. This is surprising since deficits in the nicotinic receptor system have been repeatedly associated with the cognitive deficit that occurs to neurodegenerative conditions such as Alzheimer's disease and Parkinson's disease. Our initial studies clearly demonstrate that a cortical contusion injury (CCI) causes significant and widespread defects in hippocampal and cortical alpha 7 nicotinic receptor (nAChr) expression. The working hypothesis of the proposed studies is that changes in the CNS alpha7 nAChr's contribute significantly to head trauma- induced cognitive dysfunction. Furthermore, we predict that pharmacological modulation of alpha7 neuronal nicotinic receptors will have neuroprotective and cognitive-enhancing properties in head-injured rats. The Specific Aims of this proposal will evaluate: 1) the time course of changes in alpha7 protein and message expression following TBI 2) neuroprotective actions of nicotinic receptor antagonists administered in the acute phase of TBI, 3) cognitive enhancing properties of nicotine and selective alpha7 agonists administered acutely (or chronically) in the delayed phase of TBI 4) the effects of TBI on deficits in auditory sensory gating

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and 5) restoration of sensory gating following treatment with nicotine and other selective alpha7 agonists. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COGNITIVE ORTHOSIS WITH INTERACTIVE TASK AND PLANNING Principal Investigator & Institution: Lopresti, Edmund F.; President; At Sciences 160 N Craig St, Ste 117 Pittsburgh, Pa 15213 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-MAY-2005 Summary: (provided by applicant): Patients with acquired cognitive impairments such as those associated with traumatic brain injury or stroke experience difficulty maintaining daily schedules and performing the sequential steps required to complete the activities that comprise those schedules. In order to address the needs of these persons, we propose to develop a cognitive orthosis system, called Solo, to aid cognitively impaired clients and their caregivers in managing their daily tasks. Solo will allow a caregiver to organize a client's tasks into a daily schedule and will instruct the client in how to perform tasks in the schedule. Solo will offer a number of innovations compared to currently available cognitive orthotic technology. For the caregiver, Solo will provide a greater capability to specify the individual steps within an activity, and to perform management and monitoring of the client's performance. The client will experience a greater ability to interact with the device, providing information about his or her situation and receiving instructions that are pertinent to the client's context and problems which he or she may be experiencing. Solo will also provide automatic assistance in revising the client's schedule as situations change (e.g., appointments run over expected times or need to be rescheduled). This research builds on the investigative team's previous experience with the design and evaluation of cognitive orthosis technology, clinical experience with individuals who have cognitive impairments, and experience with interactive activity guidance systems for people with typical cognitive abilities in extraordinary conditions (i.e., astronauts). Evaluation of the Solo system will be conducted through focus groups and usability tests with clinicians, and clinical trials with individuals who have cognitive impairments. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: COGNITIVE RECOVERY AFTER TRAUMATIC BRAIN INJURY Principal Investigator & Institution: Schmitter-Edgecombe, Maureen; Psychology; Washington State University 423 Neill Hall Pullman, Wa 99164 Timing: Fiscal Year 2004; Project Start 15-APR-2004; Project End 31-MAR-2008 Summary: (provided by applicant): Traumatic brain injury (TBI) is a disorder of public health concern that has ramifications not only for the individual, but also for their family, the public health system, and the economy. The majority of TBIs affect people in the prime of their vocational productivity. Despite decades of work in the area of cognitive rehabilitation, a recent evidence report summarizing research on the efficacy of cognitive remediation after TBI revealed predominately negative results. This is partly because there is currently no empirically supported theory about cognitive recovery from TBI to guide intervention strategies. This study will provide better scientific evidence to guide cognitive remediation by more fully characterizing the potential early learning mechanisms of TBI patients, and by prospectively evaluating the recovery trajectories of both automatic and controlled cognitive processes. TBI patients will complete experimental tasks designed to assess automatic and more controlled

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components of visual search, semantic priming, and memory. These task will be administered following the TBI patients emergence from post-traumatic amnesia, and then again at 2-, 6-, and 12-month intervals. Control participants will complete the tasks at similar intervals following baseline testing. Perceptually-based implicit learning abilities and memory-based skill learning abilities will also be evaluated acutely following injury. If restitution of function of automatic processes occurs early in recovery and before controlled processes, then training techniques that tap into residual automatic skills or capitalize on processes that can be made automatic through practice could prove vital for early interventions, facilitating recovery and improving ultimate cognitive outcome. Furthermore, an understanding of the recovery trajectories of automatic processes could help refine models for predicting rehabilitative gains and aid in rehabilitative planning and resource allocation as automatic processes often serve as a "data base" for more controlled processes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CONTROLLED TRIAL OF SERTRALINE FOR DEPRESSION AFTER TBI Principal Investigator & Institution: Bombardier, Charles H.; Associate Professor; Rehabilitation Medicine; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 20-SEP-2000; Project End 31-MAY-2005 Summary: Persons with traumatic brain injury (TBI) experience high rates of depression, especially during the first six months following their injuries. Neurological and psychosocial factors appear to contribute to depression in this population. Depression following TBI is associated with poor cognitive, behavioral, and functional outcomes. Preliminary studies suggest that people with TBI and major depression may not respond to antidepressant treatment in the same way as depressed persons without TBI, post TBI depression may respond well to selective serotonin reuptake inhibitor (SSRI) antidepressants, that and effective antidepressant treatment is associated with improvements in health status, neuropsychological function, and post-concussive symptoms. No large randomized placebo-controlled studies have been conducted and basic questions remain about the treatment and outcomes of major depression among persons with traumatic injury. As a consequence, depression is not usually assessed after traumatic brain injury, and optimal rehabilitation guidelines for identifying and treating depression have not been established. To address this gap, the proposed study would follow a large consecutive sample of persons hospitalized for moderate to severe TBI to identify those who develop major depression. With those who develop major depression, a 12-week, randomized, double-blind, controlled trial of sertraline would be conducted. The trial would test the hypothesis that sertraline reduces depression related symptoms, as measured by the Hamilton Rating Scale for Depression. Secondary hypotheses to be tested include whether sertraline leads to greater improvement in neuropsychological test performance, post-concussive symptoms and self-reported health status as measured by the SF 36. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CORE--IMAGING FACILITY Principal Investigator & Institution: Videen, Tom O.; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2003; Project Start 15-AUG-2003; Project End 31-MAY-2008

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Summary: The Imaging Core has two purposes: (1) to perform acquisition, reconstruction, processing and archiving of the PET, MR and CT data for Projects 1,2 and 3. and (2) to validate recently developed MR methods of cerebral blood flow (CBF) and oxygen extraction fraction (OEF) estimation against gold-standard techniques. All PET studies will be performed on the Siemens 961 ECAT EXACT HR 47 PET scanner located in the Neurocritical Care PET Research Facility in the Neurology Neurosurgery Intensive Care Unit. This facility is dedicated to scientific research with studies of acute brain injury given top priority. It is outfitted with all the life support equipment available elsewhere in the NNICU. Clinical CT and MR studies from projects 1,2 and 3 will be performed on clinical equipment at Barnes-Jewish Hospital. Barnes-Jewish Hospital and Washington University School of Medicine have a long and successful collaborative arrangement for clinical imaging research. Currently, a formal agreement exists between Barnes-Jewish Hospital and the Mallinckrodt Institute of Radiology to use the hospital's clinical equipment for research purposes. After approval by the Research Committee, investigators are authorized to use the facilities as necessary to carry out research including access at short notice to study patients with acute disease. Image files are easily transferred through the hospital's electronic radiology system directly to the computer processing facilities in the East Building. We have successfully used this system over the past 6 years to study patients with acute ischemic stroke, intracerebral hemorrhage and traumatic brain injury. The clinical CT and MR studies described in this proposal have been approved through this mechanism. Validation of MR methods will be carried out in non-human primates in the East Building Imaging Research Facility by performing the following specific aims: (1) To develop a software package for obtaining quantitative estimates of MR CBF, OEF, and CMRO2 (2)To validate MR-measured CBF against a Kety-Schmidt technique under a range of experimental conditions in non-human primates (3)To validate MR-measured whole brain OEF against direct measurements of cerebral arteriovenous oxygenation difference (A-VDO2) in non-human primates. These validation studies will provide the basis for future studies of human pathophysiology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CORE--OUTCOME MEASURES AND CELL PREPARATION Principal Investigator & Institution: Gautam, Subhash C.; Senior Staff Investigator; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2003; Project Start 15-JUL-2003; Project End 31-MAY-2008 Summary: Core B provides the cells to be employed for treatment as well as the essential outcome measurements for all constituent projects of the Program Project. Neurologic function and behavior are the primary outcome measures for Project 1 (Treatment of Stroke with MSCs) Project 2 (Treatment of Traumatic Brain Injury with MSCs) and are extensively employed in Project 3 (Analysis of MSC Interaction with Tissue). In this core, we describe the sets of functional tests to be employed in evaluating response to MSC therapy. Included in the battery of tests are, motor and somatosensory tests, and neurological scales. Projects 1-3 also address the fate of the injected MSCs, the factors produced by these cells and their effect on cerebral tissue that promote improved functional outcome, and the effects of MSCs on the endogenous parenchymal cells. This core provides all the resources required for cellular identification, measurement and identification of trophic factors, and microscopy. All three projects employ marrow stromal cells. Core B, provides the facilities and personnel dedicated to the production and characterization of these cells. Focusing resources needed for the component

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projects in Core B, allows for efficient and effective utilization of resources essential for all three projects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CORTICAL EXCITABILITY AFTER TRAUMATIC BRAIN INJURY Principal Investigator & Institution: Golarai, Golijeh; Neurosciences; University of New Mexico Albuquerque Controller's Office Albuquerque, Nm 87131 Timing: Fiscal Year 2002; Project Start 01-APR-1999; Project End 31-MAR-2004 Summary: (Applicant's abstract) Traumatic brain injury (TBI) leads to severe and lasting disabilities in sensorimotor and cognitive functions in 30,000 to 50,000 people in the United States each year. Approximately one third of individuals with serious head injuries eventually develop epilepsy. As TBI largely afflicts young people, health care and lost income are more costly than for stroke or degenerative diseases that typically affect the elderly. Clearly, interventions to prevent epilepsy, while promoting recovery from primary deficits after TBI, would be of great social value. Accordingly, this proposal examines the development of epileptogenic cellular physiology in rat sensorimotor cortex after a controlled injury, using a combination of extra-and intracellular electrophysiolgy, voltage- and calcium imaging, and histological methods. The experiments will also include an examination of the neuromodulatory role of noradrenaline (NA) after TBI for two reasons. First, NA plays a complex role in both suppressing and promoting epileptogenesis. Second, NA with physical therapy (NA/PT) is the only pharmacotherapy that has enhanced functional recovery in doubleblind studies of patients with well-established brain injury. This proposal represents a synthesis of my ongoing interest in basic mechanisms of epilepsy (which I have explored in hippocampus) and my career goal of expanding my area of research to include the neocortex, intracellular electro-and calcium physiology, and pathophysiology of head trauma. This project, including the mentorship of J.A. Connor and the collaboration of D.M. Feeney and R.C. S. Lin, will allow me to establish myself in these new areas, wile drawing on my experience with the kindling and kainate models of epilepsy, with various histological methods, with electrophysiolgy in vivo, and with the voltage-imaging techniques that I have learned with J.A. Connor. I will work with three senior scientists who have made major contributions to the fields of neuronal calcium and electrophysiology (Connor), TBI and NA/PT (Feeney) and anatomical correlates of neuopathophysiology (Lin). This rare interdisciplinary research opportunity will allow me to contribute to the understanding of post-traumatic epilepsy while increasing my breadth and depth as a scientist. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CORTICAL PLASTICITY: MECHANISMS AND MODULATION Principal Investigator & Institution: Hodge, Charles J.; Neurosurgery; Upstate Medical University Research Administration Syracuse, Ny 13210 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2007 Summary: (provided by applicant): Stroke and traumatic brain injury afflict more than 600,000 Americans annually, resulting in some level of functional impairment. While stroke afflicts primarily an adult population, traumatic brain injury affects mostly children and young adults. Variable recovery of function and some dysfunction will occur in most patients due to the innate ability of the nervous system to reorganize. This process is known as plasticity. Recent studies demonstrate a dramatic improvement in the speed and extent of behavioral recovery after brain injury by the use of the

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neurostimulant amphetamine. In contrast, phenytoin, a commonly administered antiseizure medication, retards recovery. Although the effects of these drugs have been demonstrated on behavioral recovery in both animal models and humans, their influence on mechanisms of plasticity remains largely unknown. The purpose of this project is to determine mechanisms that govern plasticity in a well-characterized rat model of cortical injury that results in a well-defined plastic response observed through functional optical imaging techniques. We propose to: * Evaluate the modulation by damphetamine (stimulant) and phenytoin (depressant) on functional cortical reorganization in the rat whisker/barrel cortex following a focal excitotoxic injury, utilizing intrinsic optical imaging. * Examine changes in gene expression that are associated with plasticity using "gene chip" techniques in individual affected and spared cortical barrels to decipher the genetic response underlying observed functional outcomes and to gain insight into mechanisms by which d-amphetamine alters recovery following injury. * Determine whether structural alterations in the intra-cortical or thalamocortical connectivity correspond to observed functional changes using neural pathway tracing techniques. Functional imaging techniques allow us to determine the extent and time course of plastic changes in a longitudinal fashion. Our studies will elaborate critical aspects of cortical plasticity in terms of underlying gene expression, structural and functional reorganization following focal cortical injury. The determined responses will be modulated by pharmacologic agents in common clinical usage. The insight gained from these studies will help determine most effective management of patients to maximize recovery from brain injury. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CPP MANAGEMENT INFORMATION FEEDBACK AND NURSING Principal Investigator & Institution: Mitchell, Pamela H.; Elizabeth S. Soule Professor and Associa; Physiological Nursing; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2004; Project Start 01-APR-1999; Project End 31-MAR-2008 Summary: (provided by applicant): This study is predicated on the assumption that there may be optimal levels of cerebral perfusion pressure (CPP) and its components, intracranial pressure (ICP) and systemic arterial blood pressure (ABP), that help prevent or reduce secondary brain injury in critically ill patients. Since CPP can be influenced by nursing care such as positioning, suctioning and the like, refining the ability for nurses to manage CPP on a minute-to-minute basis is currently being tested for the ability to demonstrate measurable improvement in short and long-term outcome for late adolescents and adults. In this competing continuation, we propose to extend the observation to children, for whom no adequate threshold has yet been determined, to examine complexity of physiologic waveforms to better understand the variations that may underlie clinical outcome differences or better predict outcome variation, and to conduct a cost-analysis of this improvement in technology. The specific aims of the competing continuation are to: 1) Determine if CPP threshold can be defined for children less than 16 years of age, based on 3, 6 and 12 month outcomes; 2) Characterize ICP and ABP complexity and HRV for both adults and children in relation to predicting outcome at discharge and 6 and 12 months (for children); 3) Estimate hospitalization cost across the life span for children, adolescents and adults monitored for CPP; 4) Estimate the value, in quality adjusted life years (QALY) for varying outcomes of care across the life span for children, adolescents and adults monitored for CPP. Computer interfaces that provide visual information about CPP will be allocated to beds in each of the pediatric intensive care units used for children ages 1-16 years with traumatic injury,

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in whom ICP and blood pressure monitoring has been instituted as part of medical management. Data regarding CPP and 3, 6 and 12-month functional outcome will be evaluated to determine if a threshold for CPP can be determined for differing grades of outcome (from death to very good physical and social function). Continuous ICP, ABP and electrocardiographic data from these children and from the adults in the parent study will be analyzed using a variety of non-linear approaches to determine waveform factors that are predictive of outcome. Hospital data regarding costs and charges during acute care hospitalization will be examined in both children and adults to determine if the use of the computer interface is associated with greater or lesser acute care costs. Finally, a survey of survivors of acute brain injury and of community peers will be conducted to estimate the value (in quality adjusted life years) placed on differing outcome states after both traumatic brain injury and aneurysmal subarachnoid hemorrhage. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DEATH RECEPTORS AND TRAUMATIC BRAIN INJURY Principal Investigator & Institution: Whalen, Michael J.; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 01-AUG-2001; Project End 31-JUL-2006 Summary: (provided by applicant): Traumatic brain injury (TBI) is a leading cause of death and disability that has no specific treatment. Programmed cell death (PCD) that occurs after TBI is a potential therapeutic target, however, mechanisms that initiate PCD after TBI are not well understood. Endogenous death receptors of the tumor necrosis super-family are transmembrane proteins that can initiate PCD. Activation of death receptors leads to formation of a death inducing signaling complex (DISC) that initiates PCD by activating caspase 8 and the pro-apoptotic bcl2 family member Bid. We have generated preliminary data demonstrating up-regulation of death receptors and formation of a DISC in injured brain after TBI in mice. We hypothesize that death receptors of the TNF super-family promote neuronal death and secondary injury after experimental TBI. To examine this hypothesis we propose the following Specific Aims: 1) Extend the development of a controlled cortical impact (CCI) model of TBI in mice and characterize the delayed cell death component, 2) determine whether mechanisms of cell death after CCI involve PCD, 3) determine the co-localization and time course of expression of death receptors, their specific ligands, and other upstream mediators for initiation of caspase activation and cell death in neurons and glia after TBI, and 4) determine if strategies that inhibit death receptors or their downstream targets reduce neuropathology (contusion volume, histology) and improve functional outcome (cognitive and motor) after CCI. If death receptors such as fas and TNF-alpha play a role in PCD after TBI, then these studies may lead to specific treatments for secondary injury after TBI. This proposal will provide an opportunity for experience that is essential for my long-term goal to pursue a career in clinically related brain and cell death research. The Neuroscience Center at the Massachusetts General Hospital and the faculty at Harvard Medical School provide an outstanding training environment to study key mechanisms of TBI and cell death. This experience will be reinforced by participation in the Boston Cell Death Club and coursework offered at the Harvard Medical School. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DETERMINANTS IN RECOVERY FROM TBI IN CHILDREN 0-3 Principal Investigator & Institution: Blackman, James A.; Pediatrics; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904

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Timing: Fiscal Year 2003; Project Start 05-APR-2003; Project End 31-MAR-2006 Summary: (provided by applicant): There is great excitement and hopefulness regarding plasticity of the brain, especially in very young children. Yet, no one knows with certainty whether the immature brain is more or less vulnerable to or resilient from injury. To answer this question, age at injury must be isolated as an independent variable, a challenging task since there are multiple factors that determine outcome. It is anticipated that exploratory research in this area will lead to preventative strategies and rational therapeutic designs tailored to the unique attributes of the developing brain. In response to the NIH program announcement "Exploratory Grants in Pediatric Brain Disorders: Integrating the Science" we propose a pilot project to refine the methodology and determine an appropriate sample size for an adequately powered multi-centered study. The primary hypothesis is that TBI at a younger age results in higher developmental and functional outcome scores than TBI at an older age, controlling for other relevant variables. Additional hypotheses examine the predictive value of the Apolipoprotein E gene, neuron specific enolase, and protein S100B. Eighty children 3 years-of-age or younger, admitted to the hospital for traumatic brain injury, will be enrolled in a pilot study over two years with follow-up at 6 and 12 months post injury. An extensive database on demographics, pre- and in-hospital course, imaging and laboratory studies, and a detailed interview of the parent/caretaker/observer will be completed. DNA will be analyzed for APO E alleles at Duke University and two samples of blood obtained 12 hours apart will be analyzed at the University of Pittsburgh for NSE and a protein S100B. At 6 and 12 months post injury, subjects will receive detailed neurological, sensory, developmental, behavioral, and functional assessments using standardized instruments. This pilot project is an attempt to enhance our scientific knowledge in understanding the pathobiology and treatment of brain injury in infants and toddlers. It addresses explicit areas of interest in the PA: injury to the developing brain, plasticity, and outcomes of age-specific injury. This project will be far more comprehensive than previous studies of brain injury in infants and toddlers and will explore novel hypotheses regarding genetic determinants of outcome and markers of neuronal injury in young children. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DEVELOPING A COMPUTER ADAPTIVE TBI COGNITIVE MEASURE Principal Investigator & Institution: Velozo, Craig A.; Associate Professor; Occupational Therapy; University of Florida Gainesville, Fl 32611 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-MAR-2007 Summary: (provided by the applicant): Cognitive functional status measures are critical tools for research on the effectiveness of rehabilitation interventions for traumatic brain injury (TBI). Global functional measures are widely used in rehabilitation settings, but only provide a cursory evaluation of cognition. Traditional neuropsychological measures, while standardized and psychometrically sound, are lengthy and often criticized for having weak ecological validity. The purpose of this project is to build an ecologically valid item bank and computer adaptive testing (CAT) prototype for an applied cognitive measure for TBI. Modern test theory provides a basis for developing a measure that is both efficient to administer and precise for assessing cognition along the continuum of TBI recovery. Item Response Theory methodologies, specifically Rasch analysis, can be used to calibrate items thereby providing a means to match item difficulties to cognitive ability levels across stages of TBI recovery. CAT technology provides a mechanism to administer a small number of items to an individual, based on

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his/her cognitive ability level. This planning proposal will accomplish the following: First, conduct literature reviews of existing instruments and theoretical models of TBI recovery to guide creation of a large item bank (300-500 items) reflecting cognitive behaviors commonly observed throughout TBI recovery. Second, health care professionals, patients and caregivers will be interviewed to expand and fine-tune the item bank. Third, a paper and pencil version of the instrument will be pilot tested on 50 patients in acute hospitalization, inpatient/outpatient rehabilitation and 6-months post rehabilitation. Self-report, therapist and caregiver administrations of the instrument will be compared to a "gold standard" abbreviated neuropsychological assessment to identify the most appropriate rater at each stage of recovery. Finally, a web-based CAT prototype of the instrument will be developed and administration feasibility will be determined by feedback following healthcare professional, patient and caregiver administration. This planning grant will result in the item and CAT development necessary for reliability, validity and sensitivity testing of the TBI cognitive measure in a multicenter trial. The long-term objective is to develop an efficient, precise and ecologically valid instrument to evaluate outcomes of TBI interventions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DEVELOPING A RAT MODEL OF POSTTRAUMATIC EPILEPSY Principal Investigator & Institution: Schwartzkroin, Philip A.; Professor; Neurological Surgery; University of California Davis Sponsored Programs, 118 Everson Hall Davis, Ca 95616 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-JAN-2006 Summary: The goal of the current application is to develop a rodent model of posttraumatic epilepsy. The importance of such a model arises from two related but separate observations: 1) Post-traumatic epilepsy is of considerable clinical concern. The population of individuals with traumatic head injury has a significantly higher risk of developing epilepsy than the uninjured population. 2) Post-traumatic epilepsy is often associated with a variable "latent" period between injury and appearance of a clinical seizure disorder. This latent period provides an important window into potential epileptogenic processes that can be targeted with new anti-epileptogenic therapies. While there is a large body of research focusing on traumatic brain injury (TBI), there has been surprisingly little experimental/animal model work on post-traumatic epilepsy. This gap is likely due, at least in part, to the difficulty in demonstrating a chronic epileptic condition in rodents (rats or mice) following experimental manipulations that produce traumatic brain injury (e.g., fluid percussion, weight drop, controlled cortical impact). Investigators have produced chronic seizure states in rats following status epilepticus, but at best have produced a more seizure-prone animal (lower seizure threshold) following TBI. We propose to develop a rat model of TBI in which a latent period is followed by a chronic seizure state. We will approach this goal initially by manipulating key variables of controlled cortical impact (CCI) (e.g., position of impact, degree of penetration), Based on the neuropathology mostoften associated with status epilepticus models, we hypothesize that TBI insults that result in s!gnificant damage to ventral hippocampus, and/or in bilateral hippocampal injury and reorganization, will result in chronic seizure activity - especially if the injury is associated with significant post-trauma hypoxia. Once a reliable model has been developed, we will begin to assess the contributions of predisposing factors (e.g., genetics, early insult) to the establishment of a post-traumatic epileptic condition. Determination of seizure activity in animals with TBI will be carried': out using longterm video/EEG telemetric monitoring. In addition, animals will be tested for seizure

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threshold (latency to flurothyl-induced seizures). Treated and tested animals will be sacrificed for histological analysis of damage. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DOSING & SAFETY TRIALS USING CSA IN SEVERE HEAD INJURY Principal Investigator & Institution: Young, a B.; Johnston-Wright Chair of Surgery; Surgery; University of Kentucky 109 Kinkead Hall Lexington, Ky 40506 Timing: Fiscal Year 2002; Project Start 01-JUN-2001; Project End 31-MAY-2004 Summary: Head injury is a complex disease where the primary injury initiates a chemical cascade of central mediator release leading to secondary insults within the central nervous system and systemically. Morbidity and mortality rates remain high despite advances in guidelines for clinical management. Several potential mechanisms of secondary injury have been identified and therapeutic strategies for intervention have been tested in animal and human trials. Despite preliminary evidence of efficacy in small clinical trials, no drug has shown significant benefit when tested in larger well designed randomized investigations. Lack of pharmacokinetic data to guide dosing for specific pharmacodynamic endpoints is one of several possible reasons for failure of investigational drugs to demonstrate benefit. Recent evidence from animal research suggests a protective effect of Cyclosporin A (CsA) in neural trauma. CsA given to mice and rats following severe cortical contusion reduced neuronal injury by approximately 50%. CsA is a difficult drug to model and predict response. Our preliminary data from two TBI patients demonstrates a marked variability in serum trough concentrations of CsA. The systemic effects of head injury and the requirement for adequate delivery of drug to the injured brain mandate preliminary dose finding studies prior to progressing into clinical trials. In this pilot clinical trial, we will systematically define CsA pharmacokinetic and pharmacodynamic endpoints in a homogenous population of patients with traumatic brain injury. We will measure serum and cerebrospinal fluid (CSF) concentrations of drug and surrogate biochemical markers of secondary injury to identify potential pharmacodynamic endpoints useful in designing optimal drug dosing strategies. This dose-finding proposal will characterize the pharmacokinetic profile of CsA and provide preliminary safety data in patients with TBI. Information from this pilot study will be used to establish a dosing strategy for a future Phase 11 prospective randomized trial. We will test the hypothesis that clinically approved doses of CsA can be safely administered to patients with TBI and achieve measurable concentrations in the CSF and serum. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EARLY HEMICRANIECTOMY TO MANAGE TRAUMATIC BRAIN INJURY Principal Investigator & Institution: Coplin, William M.; Associate Professor; Neurology; Wayne State University 656 W. Kirby Detroit, Mi 48202 Timing: Fiscal Year 1999; Project Start 18-JUL-1999; Project End 31-DEC-2004 Summary: Severe blunt traumatic brain injury (TBI) is a major cause of mortality and long-term disability in previously healthy young adults. The current standard of initial surgical care includes evacuation of intracranial hematomas, and, often amputation of swollen confused brain. The rationale for the latter intervention is that further edema in this area of presumed unsalvageable cerebrum will cause intracranial hypertension, impeding blood flow to otherwise more health areas of brain, with resultant infarction. To this end, modern neuro-tensive care expends great effort to control intracranial

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pressure (ICP) and prevent such secondary injury. While effectively reducing ICP, past non-randomized investigations have employed hemicraniectomy at later times, for refractory ICP, and have lacked standardized surgical and/or medical protocols and outcome measures. This randomized pilot study seeks to address the safety and possibly preliminary efficacy of early hemicraniectomy (as the initial surgical intervention) for managing patients with severe TBI. Goals include: 1) reduced therapeutic intensity for ICP over a shorter length of stay (LOS), 2) reduced need for repeat computer tomography (CT) scans and returns to the operating room (OR), and 3) improved neurological outcome. The study will randomly assign, within 24 hours of ictus, 92 TBI patients, Glasgow Coma Scale score less than or equal to 9, with midline shift greater than the size of a surgically removable hematoma. Group I will receive standardized hemicraniectomy; Group II will undergo traditional craniotomy with or without brain amputation, at the discretion of the attending neurosurgeon. I both groups, hematomas greater than or equal to 20 cc will be evacuated, a standardized medical protocol will be followed, and daily monitoring will assess neurological status and ICU therapeutic intensity. The primary outcome measure is the six-month Glasgow Outcome Scale. Secondary outcome measures include the Disability Rating Scale, Functional Independence Measures, and the SF-36 Health Survey o to one year after TBI (to assess quality of live for survivors), the duration and frequency of elevated ICP episodes, ICE Therapeutic Intervention Severity Scores, returns to CT and the OR, and ICU and hospital LOS. We hypothesize that, while both surgical therapies will initially effectively treat intracranial hypertension, the hemicraniectomy group will experience improved neurological outcome, and a reduced intensity of cre to control ICP. These data will prepare us for a full-scale multi-center outcome study of early hemicraniectomy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EFFECT OF SPINAL CORD STIMULATION ON CEREBRAL BLOOD FLOW Principal Investigator & Institution: Sagher, Oren; Neurosurgery; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 25-JAN-2001; Project End 31-DEC-2004 Summary: Spinal cord stimulation (SCS), a widely used modality for the treatment of chronic pain, is also known to have a significant vasodilator effect on peripheral vasculature. Interest in the vascular effects of SCS has resulted in its use to treat both peripheral limb ischemic and angina. Similar effects of SCS on cerebral blood flow have also been suggested. However, the significance, character and underlying mechanisms of the cerebrovascular effects of SCS remain unclear. The accompanying proposal will delineate the cerebrovascular effects of SCS in an animal model and examine the mechanism(s) that may be involved. We will also examine the feasibility of using SCS in the prevention of cerebral infarction. Specifically, we will test the following central hypotheses: I. SGS significantly enhances global cerebral blood flow (CBF) II. Cerebrovascular effects of SCS are related to changes in sympathetic tone III. Cerebrovascular effects Of SCS involve activation of brainstem/cerebellar vasomotor centers IV. Trigeminovascular innervation of cerebral vasculature mediates SCS effects on CBF V. SCS has a neuroprotective effect in the setting of focal cerebral ischemic We will utilize an in vivo model of SCS and CBF measurement in rats in order to obtain information about the magnitude, time course, and spatial characteristics of CBF changes induced by SCS. Using this model, we will also investigate the effects of SCS on stroke induced by focal cerebral ischemic. An understanding of the mechanisms

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involved in the cerebrovascular effects of SCS has direct ramifications in the treatment of conditions where cerebral blood flow is compromised, such as stroke, cerebral vasospasm and traumatic brain injury. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EFFECTS OF DIHYDROEPIANDROSTERONE ON BRAIN INJURY Principal Investigator & Institution: Hoffman, Stuart W.; Emergency Medicine; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2004 Summary: (provided by applicant): At present, there is no effective pharmacological agent to enhance neurobehavioral recovery after traumatic brain injury (TBI). The longterm objective of this research is to develop a safe and effective treatment that would enhance neurorehabilitation after traumatic injuries to the central nervous system. After the initial cascade of destructive events occurs, the brain is in a state of dysfunction due to injured neurons, disrupted synapses, continuing inflammatory responses, and decreased neuronal activity. However, the brain has the capability to recover significantly from this post-injury state, if proper behavioral or pharmacological therapies are administered. In this proposal, it is the investigators'goal to demonstrate that dihydroepiandrosterone (DHEA) will significantly increase recovery of function. DHEA is a special type of steroid hormone that is synthesized both inside and outside of the nervous system in both males and females. DHEA, a known neurosteroid, can stimulate the formation of new synapses, modulate the immune system, and increase neuronal activity involved in cognitive function. These same characteristics make DHEA worth considering as potential therapy to facilitate recovery of cognitive function after brain injury. In addition, long-term administration of DHEA has shown that it produces no adverse side-effects in rodents or humans. In this proposal, the investigators will investigate whether DHEA can promote a more complete recovery of function after experimental TBI. The investigators will use a controlled cortical impactor to create bilateral medial frontal contusions in rats to model TBI. The investigators goals will be to: (1) determine whether DHEA can promote functional recovery in both males and females, a subject that has received virtually no attention in the experimental literature; (2) determine the most effective dose of DHEA; (3) determine whether treatment with DHEA can affect the morphology and survival of neurons as well as the proliferation of glial cells; and (4) determine if the effects of DHEA on recovery of function can produce a dose dependent causal effect on histological measures. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EFFECTS OF O2 RADICALS AND PERIVASCULAR NERVES IN TRAUMA Principal Investigator & Institution: Dewitt, Douglas S.; Professor; Anesthesiology; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2002; Project Start 01-DEC-1986; Project End 31-JAN-2004 Summary: (Verbatim from the Applicant's Abstract) Traumatic brain injury (TBI) increases cerebral vascular resistance, damages cerebral vascular endothelial cells and the blood brain barrier and reduces cerebral vasodilatory responses to hypotension, hypoxia and hemodilution. Our overall hypothesis is that traumatic brain injury increases superoxide anion radicals which react with increased NO to form OONO-, impairing the function of cerebral vascular smooth muscle and perivascular nerves. Aim 1 is to determine the association between NO, O2-, and CBF decreases after traumatic

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brain injury. NO, superoxide, and CBF will be measured in rats after moderate traumatic brain injury. Studies will be done to see if arginine supplementation restores CBF despite increases in O2- production. Immunohistochemical staining for nitrotyrosine will be used to determine if TBI and L-arginine treatment increases OONO- production. Aim 2 is to determine if traumatic brain injury reduces the activity of eNOS and/or increases the potentially damaging iNOS and nNOS isoforms, using arginine to citrulline conversion assays with specific inhibitors and mRNA expression studies. Aim 3 is to determine if traumatic brain injury affects the cerebral vascular responses to endothelium-dependent vasodilator ACh, activators of ATP-sensitive potassium channels like aprikalim, or reduced perfusion pressure, using arteries harvested following traumatic brain injury. Aim 4 is to determine the effects of TBI and OONO- exposure on perivascular vasodilatory neurotransmitters CGRP, ACh, and anadamide. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EFFECTS OF VITAMIN B3 ON TRAUMATIC BRAIN INJURY Principal Investigator & Institution: Hoane, Michael R.; Psychology; East Carolina University 1000 E 5Th St Greenville, Nc 27858 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-JAN-2005 Summary: (provided by applicant): Annually, approximately 2 million Americans suffer a moderate to severe traumatic brain injury (TBI). These injuries produce enduring disabilities that include cognitive, sensory, motor, and emotional impairments. The associated health care costs from these injuries are staggering. Confounding this major public health issue is the fact that currently there are very few pharmacological treatment options for patients who have suffered TBI. In part, this occurs because many newly synthesized drugs fail in various stages of efficacy testing. Given the fact that newly synthesized drugs fail in clinical trials it seems reasonable to begin to examine the potential efficacy of more natural substances. It has recently been demonstrated that administration of vitamin B3 (B3) following experimentally induced stroke reduces the size of the infarct and can improve behavioral outcome in rats. In addition, the preclinical efficacy of magnesium pharmacotherapy has been well established. The proposed research will investigate the potential preclinical efficacy of B3 to lessen the physiological consequences of brain injury and improve behavioral outcome. We will use the rodent bilateral frontal cortical contusion injury model, which is similar to a frontal head injury sustained in a car accident. The specific aims of this study are to: 1) determine if administration of B3 following injury can significantly reduce the cognitive and sensorimotor impairments seen following TBI; 2) determine the best injections parameters (i.e., window of opportunity and dose response) for B3 pharmacotherapy following TBI; 3) determine if administration of B3 following injury can significantly decrease the amount of injury-induced edema and injury-induced magnesium depletion; 4) determine the effect of B3 pharmacotherapy on apoptosis and reactive gliosis following TBI. The research proposed here will determine if B3 holds any preclinical efficacy for the treatment of TBI and begin to define the parameters for the development of B3 as a clinical treatment for TBI. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EFFICACY OF HYPOTHERMIA IN PEDIATRIC TBI Principal Investigator & Institution: Adelson, P David.; Neurological Surgery; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260

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Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2005 Summary: Treatment of traumatic brain injury (TBI) in the pediatric population has been totally dependent on adult paradigms, both experimentally and clinically with little attention paid to the potential unique responses of the developing brain after injury. There has been few experimental studies utilizing immature animals and even fewer clinical studies utilizing treatment interventions following pediatric TBI (e.g.) Hypothermia (HYPO). While there is over-whelming experimental evidence that HYPO is neuroprotective in a wide spectrum of different models of TBI, studies in children or utilizing immature models of TBI have been lacking. It is obvious that despite the evidence available in the adult, so little is known of the effect of HYPO following experimental and clinical pediatric TBI that it necessitates further study. Despite the recent disappointing results from the adult clinical trials using hypothermia, there was a suggestion of improved outcome in younger patients that may extend to the pediatric population. Efficacy from this study through cannot be translated to care of children since none of the patients in this trial were children and HYPO following pediatric TBI cannot be either prematurely discarded or utilized as a therapeutic intervention without further study. Based on the previous literature and our Preliminary Data, HYPO may be potentially more beneficial in children as compared to the adult. This initial data is compelling evidence for further study as to the potential children, there is currently no understanding of the potential age dependent impact nor limitations of HYPO treatment following pediatric TBI on subsequent neural development. Our Overall Hypothesis for this proposal is that while HYPO will be beneficial in the treatment of pediatric TBI, it will have an age related impact on development at different ages of injury and treatment. This age at injury and treatment effect will in turn be governed by the sensitivity of the developing brain to neurotransmitter release and/or subsequent blockade. While HYPO following experimental and clinical pediatric TBI will positively impact on the attenuation of neurotransmitter release in all maturational ages, an age related effect, due to either inadequate blockade of excessive neurotransmitter release or the negative impact of neurotransmitter blockade on normal development, will be evidenced in post-injury markers of cell death, synaptic connectivity, and cognitive function. The Specific Aims will include defining the neurotransmitter release response following treatment with HYPO and the subsequent age related impact of injury and treatment of histologic damage, both early and delayed neuronal cell death, synaptogenesis, and functional outcome using different age at injury experimental models of TBI in the immature rat. Parallel clinical specific aims will define the effect of neurotransmitter release in response to treatment with HYPO and the age-related impact of HYPO on early and delayed cell death in children. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EICOSANOIDS AND NO IN CEREBROVASCULAR THROMBOSIS Principal Investigator & Institution: Wu, Kenneth K.; Professor and Director; Internal Medicine; University of Texas Hlth Sci Ctr Houston Box 20036 Houston, Tx 77225 Timing: Fiscal Year 2002; Project Start 01-AUG-1985; Project End 31-JAN-2004 Summary: This program proposes an interdisciplinary effort to broaden our understanding of the roles of mediators such as eicosanoids and nitric oxide in the pathogenesis of cerebrovascular thrombosis and brain injury and to enhance our knowledge on the regulation on the regulation and augmentation of their synthesis. Our major goal is to elucidate the fundamental mechanisms by which important endothelial and neuronal genes are regulated and to bring these basic investigations in clinical applications in improved care of patients with cerebrovascular thrombosis and brain

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injury. Substantial progresses have been made during the previous and present funding periods. These progresses contribute significantly to the rapid advance in this area of research. In this renewal application, we will pursue ongoing project ongoing projects and add new areas of research. Four projects and two core units are proposed. Project 1, Regulation of Eicosanoid Biosynthesis, is a continuing project aimed at characterization of the transcriptional regulation of endothelial COX-1 and PGI synthase genes. Project 2, Induction of NOS-3 and COX-2 by Vasoprotective agents, is an extension of project 1. It aims at elucidating the mechanism by which lysophosphatidylcholine and estrogen induces housekeeping NOS-3 and inducible COX-2 genes. Project 3, Role of Cox-2 in Brain Trauma Pathophysiology, proposes to test the hypothesis that COX-2 induction contributes to traumatic brain injury pathophysiology, and anti- inflammatory agents, methylprednisone and IL-10 attenuates COX-2 expression. Project 4, Structure-Function Relationships of TXA2 and PGI2 Receptors, is an extension of project 2 of the current program. It proposes to use a combination of biochemical, biophysical and molecular genetic techniques to map the ligand binding sites of these two receptors. Core A provides administrative coordination and Core B laboratory support for all projects. Thus, the scope of this program ranges from structural biology, cellular and molecular biology to in vivo animal models and there exists an exciting potential for a rapid application of basic information to clinical management of stroke and brain injury and vice versa. The program involves professional personnel who have a long standing interest in thrombosis and stroke research with diverse but complementary expertises in vascular biology, hematology, neurology, neurobiology, biochemistry, cell-molecular biology, structural biology, enzymology and pharmacology. There is an active interaction among investigators. This program has a tract record for cultivating trainees and young investigators. It is intended that this program will enable several laboratories to work individually and together to achieve the highest degree of innovating and productivity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ESTROGEN, NADPH OXIDASE, AND NEUROTRAUMA Principal Investigator & Institution: Bruce-Keller, Annadora J.; Assistant Professor; Sanders-Brown Ky Res Ctr/Aging; University of Kentucky 109 Kinkead Hall Lexington, Ky 40506 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-MAY-2007 Summary: (provided by applicant): Traumatic brain injury (TBI) afflicts almost 500,000 Americans a year, but unfortunately, existing treatments have only minimal ability to prevent secondary brain damage accompanying traumatic brain injury. Epidemiological data that suggests that women fare better then men following TBI, but the basis for this difference is not understood. It is likely that action of female sex hormones, particularly estrogen, may have significant effects on the progression of brain injury, and recent data from our laboratory suggests that estrogen has potent antiinflammatory properties that could account for its ability to attenuate traumatic brain injury. In particular, data indicates that estrogen is able to decrease oxidative burst activity and subsequent redox-based inflammatory signaling in glial cells, thereby attenuating neurotoxic brain inflammation. Therefore, it is proposed that estrogen acts to preserve brain function following TBI by decreasing both blood-brain barrier (BBB) breech and neuronal injury, and that these distinct endpoints are mediated by a single mechanism: modulation of the glial oxidative burst. Specific Aim 1 will test the hypothesis that estrogen is able to significantly attenuate oxidative burst activity in astrocytes, microglial cells, and endothelial cells both in vitro and in vivo, and will

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determine the role of estrogen receptors in this process through use of estrogen receptor knockout mice. Specific Aim 2 will test the hypothesis that by directly interfering with oxidative burst activity, estrogen blocks the release of matrix metalloproteinases and thus preserves blood-brain barrier integrity in mice following traumatic brain injury. Specific Aim 3 will build upon these studies by testing the hypothesis that by decreasing oxidative burst activity and redox signaling, estrogen blocks the formation of neurotoxic inflammatory mediators (excitotoxins and cytokines), culminating in decreased injury and increased recovery following traumatic brain injury. Completion of these studies will result in a thorough understanding of the mechanisms of estrogen-mediated neuroprotection in TBI and could highlight a novel target for therapeutic intervention following brain trauma in both women and men. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FUNCTIONAL MRI OF ATTENTION IN PEDIATRIC TBI Principal Investigator & Institution: Williams, Sharon E.; Psychiatry and Behavioral Sci; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2008 Summary: (provided by applicant): The overall aim of this grant proposal is to enhance the applicant's skills in clinical research in the area of pediatric cognitive abilities and neuroimaging. This will be accomplished through a program of combined education and training and completion of a research project to investigate the cognitive recovery of attention skills in pediatric traumatic brain injury using functional magnetic resonance imaging. The candidate's major goal is to expand her research abilities in the area of pediatric neuropsychology and imaging technology. At the end of the award period, the candidate expects to have: 1) enhanced her research skills and developed a programmatic line of research in the area of pediatric traumatic brain injury, 2) acquired knowledge of the techniques and acquisition of neuroimaging, and 3) developed study design and data analysis skills that are relevant to the field of imaging. The objectives of the proposed research project are to assess: a) improvement in the underlying restoration of the neural pathways of attention in children with TBI, b) lesion location and volume in children with TBI and their relationship to severity of injury and brain activation for measures of attention, and 3) similarities and differences in brain activation patterns for measures of attention in children with TBI and those with ADHD. In addition to the proposed research activity, the candidate will participate in graduate coursework in the Department of Psychology. The coursework will encompass behavioral and cognitive neuroscience and advanced statistics. She will also participate in seminars and tutorials with identified educational consultants in the areas related to her planned research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENDER DIFFERENCES IN DOPAMINE FUNCTION AFTER TBI Principal Investigator & Institution: Wagner, Amy K.; Physical Medicine and Rehabilitation; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 06-FEB-2002; Project End 31-JAN-2004 Summary: (provided by applicant): Traumatic brain injury (TBI) is an epidemic in the United States with survivors often having many decades of productive life loss. An estimated 5.3 million Americans currently live with disabilities resulting from TBI. Despite the fact that about 25% of the population with TBI are women, the large

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majority of clinical and animal research on TBI to date has been with males. Evidence shows that females have more difficulties with post-concussive symptoms and poorer outcome after TBI compared to males. It is suspected that dopamine I (DA) plays a crucial role in working memory and other aspects of executive functioning, and decreases in DA system function after TBI are thought to affect cognitive recovery. Estrogen is well known to play a significant role in dopaminergic functioning, and estrogen has been shown to have a neuroprotective effect acutely after TBI. However, no one has evaluated the effect of estrogen on DA functioning and cognitive recovery from TBI. The goal of this proposal is to evaluate the effects of estrogen on DA pathways in female rodents compared to male rodents after TBI. The effects of methylphenidate on cognitive performance and DA function in females and male rodents after experimental TBI will also be studied. The long-term goal is to delineate the role of estrogen on DA system mediated cognitive deficits in order to develop and optimize new and existing therapies that specifically target and enhance recovery of both males and females after TBI. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETICS, DYSFUNCTION

INFLAMMATION

&

POST-OP

COGNITIVE

Principal Investigator & Institution: Newman, Mark J.; Vice President; Anesthesiology; Duke University Durham, Nc 27706 Timing: Fiscal Year 2002; Project Start 30-SEP-1999; Project End 31-JUL-2004 Summary: Our investigative team has recently discovered a genetic association between late-onset Alzheimer's disease and the apolipoprotein E (APOE, gene; apoE, protein) epsilon-4 gene. This finding has triggered many recent studies showing an important role of apoE in the determination of neurologic injury and recovery following a variety of acute ischemic insults including intracerebral hemorrhage, closed head injury, acute stroke and dementia pugilistica (chronic traumatic brain injury). An important aspect of our work is the finding of an association between APOE4 and neurocognitive decline after cardiac surgery. Although mounting evidence suggests apoE plays a role in acute and chronic neurological disease, the mechanism underlying these observations and the influence of aging is not completely understood. We hypothesize that a genetic predisposition exists for the easily documented neurologic and neurocognitive dysfunction observed after anesthesia and surgery. ApoE may play a role in modulating the inflammatory response to ischemia and perioperative stress. We have recently determined that ApoE, in vivo, modulates the release of nitric oxide and TNF-alpha in glial cells. This may compound the autonomic dysregulation that we recently reported in the elderly. The combination of these two factors may modulate an exaggerated inflammatory response increasing the susceptibility to perioperative injury. Our pilot data associating APOE4 with cognitive impairment after cardiac surgery support this hypothesis. Therefore, we propose to determine the association between post-operative neurocognitive dysfunction, neurocognitive recovery, and APOE4 genotype in patients undergoing thoracic and vascular surgery. The unifying hypothesis is that a genetic susceptibility to neurologic dysfunction after surgery results either from a predisposition to immunologic dysregulation, the failure of normal genetically encoded reparative processes, or a combination of these mechanisms resulting in a greater incidence and severity of neurocognitive dysfunction and reduction in quality of life and independence in the aging population after surgery. Thus, our extensive preliminary work as well as our expanded collaborative interdisciplinary research group including cardiac anesthesiologists, cardiac surgeons, neuroscientists, geneticists

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and neurologists is uniquely able to investigate the genetic predisposition to neurocognitive dysfunction after surgery. Such an association is an important first step in elucidating the mechanism underlying genetic susceptibility to ischemic insults, and designing interventional strategies to improve outcome. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GLIAL-NEURONAL INTERACTIONS IN HEAD INJURY Principal Investigator & Institution: Gentleman, Stephen M.; Imperial College, School of Medicine Timing: Fiscal Year 2002; Project Start 01-JUN-1995; Project End 31-MAY-2007 Summary: The objectives of this Project are two-fold. First, in parallel with Project by Griffin, we will continue to study the effect of survival time and of gene polymorphisms on the manifestation of specific pathological features in traumatic brain injury which mimic the pathology of Alzheimer's disease (AD) in the belief that this will offer valuable insights into the early molecular mechanisms underlying the development of Alzheimer-type pathology. We hypothesis that the genotype of an individual modulates the extent of Abeta deposition and expression of glia-derived cytokines. Seen in the brain post-injury. Having already established that the apolipoprotein E (ApoE) genotype is important in modulating post-traumatic pathology, we will study the molecular basis of this effect in a novel in vivo paradigm of Abeta-induced neurotoxicity. Tissue from a large cohort of head-injury patients with different postinjury survival times and from non-injured control patients will be genotyped with respect to the polymorphisms in genes in the interleukin-1 gene cluster on chromosome 2. Aim 1 will determine quantitatively the changes in expression of the glia-derived inflammatory cytokines IL-1, IL-6, and S100beta throughout the brain after fatal head injury. Aim 2 will assess whether alterations in cytokine immunoreactivity following head injury are spatially and temporally correlated with changes in proteins that are important in the pathogenesis of AD. Aim 3 will determine whether inter-individual variation in the extent of the inflammatory reaction to head injury is associated withy specific polymorphisms in the genes encoding ApoE and IL-1. Aim 4 will investigate the mechanisms by which ApoE4 increases susceptibility to AD using an in vivo model of Abeta-induced neurotoxicity. Results should allow us to determine if genotype affects post-trauma pathology and will provide information on how ApoE4 produces its effects at the molecular level. The effect of genetic makeup on the extent of the inflammatory activity in the brain will be an important factor in predicting long-term sequelae of head injury (i.e., AD) and in targeting any potential therapies for the disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HEAD APPLICATIONS

IMPACT

RECORDING

TECHNOLOGY

FOR

FIELD

Principal Investigator & Institution: Greenwald, Richard M.; President; Simbex, Llc 10 Water St, Rm 410 Lebanon, Nh 03766 Timing: Fiscal Year 2002; Project Start 13-APR-2001; Project End 31-MAR-2004 Summary: The objective of this proposal is to continue research and development of a cost-effective device that measures linear and rotational head acceleration following impact in sports. Mild traumatic brain injury (MTBI) in sports is a significant public health concern. The biomechanics of head impacts that result in a concussion or other MTBI are not well understood but are widely believed to correlate with head accelerations. The lack of a system that allows researchers to measure head acceleration

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during actual play in a large number of individuals is a major obstacle in furthering our understanding of the mechanism of MTBI and its prevention. A novel algorithm for calculating linear and rotational acceleration of the head was developed and will be incorporated in a miniature accelerometer-based telemetry data acquisition system. Clinical trials will be performed at two major colleges over the course of a season in men's football and men's and women's hockey. The trial will be performed in conjunction with ongoing head injury studies that include neuropsychological testing of athletes, and neuropsychological test scores will be analyzed. The long-term goal of the project is to develop a cost-effective commercially available system for measuring head acceleration for widespread use in sports. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HEMODYNAMICS AND OUTCOME IN PEDIATRIC BRAIN INJURY Principal Investigator & Institution: Vavilala, Monica S.; Anesthesiology; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): Traumatic brain injury (TBI) is the leading cause of mortality in children over one year of age. Evidence suggests that hypotension after initial brain injury contributes to secondary brain injury and worsens outcome. Altered cerebral physiology including impaired cerebral autoregulation and hyperemia may also contribute to poor outcome following pediatric TBI. Therefore, characterizing optimal cerebral hemodynamics immediately following severe pediatric TBI is important. The objective of the proposed research is to describe the relationship between cerebral hemodynamics following severe pediatric TBI and outcome. The specific aims proposed here will provide new information regarding the early cerebral hemodynamic management of children with severe TBI. The aims are to examine (1) the relationship between cerebral perfusion pressure and outcome, (2) the relationship between persistent impairment of cerebral autoregulation and outcome, and (3) the age-related incidence of hyperemia. The investigators will also examine the relationship between hyperemia and impaired cerebral autoregulation and the relationship between persistent hyperemia and outcome following severe pediatric TBI. It is important to conduct these studies in children of various ages because (1) cerebral hemodynamics change significantly during development, (2) optimal cerebral hemodynamics following severe TBI may differ in young children compared to older children, (3) there is a paucity of physiologic data in children, and (4) pediatric practice is currently extrapolated from adult practice. The results and experience gained in this research will aid in the future study of cerebral hemodynamics in children at risk of cerebral ischemia both with and without TBI. The proposed research will be carried out at the University of Washington, well-known known for mentored patient-oriented research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HYPOPITUITARISM AFTER MODERATE AND SEVERE HEAD INJURY Principal Investigator & Institution: Kelly, Daniel F.; Associate Professor; Harbor-Ucla Research & Educ Inst 1124 W Carson St Torrance, Ca 905022052 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: (Verbatim from applicant's abstract) Pituitary function is rarely considered in the care of patients with traumatic brain injury (TBI). Yet, TBI poses significant risk to pituitary function given the gland's encasement within the sella, its delicate

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infundibular-hypothalamic structures and vulnerable vascular supply. Autopsy studies of fatal head injury victims confirm that up to one third sustain pituitary necrosis and hundreds of case reports document chronic post-traumatic pituitary failure. The longterm neurobehavioral problems that plague a majority of TBI victims are quite similar to those of patients with hypopituitarism. It is the primary hypothesis of this study that many TBI victims suffer from unrecognized pituitary dysfunction that acutely and chronically compounds the initial brain injury and limits maximal recovery. The major hypotheses being tested in this study are that i) post-traumatic pituitary failure, both acute and chronic, results primarily from a vascular insult to the pituitary gland and/or its hypothalamic-infundibular connections; ii) in the acute phase of TBI such injury can result in acute secondary adrenal insufficiency, iii) in the chronic phase of TBI such injury can result in long-term hypopituitarism, and iv) treatment of pituitary hormone deficiencies will improve neurobehavioral functioning and quality of life in the chronic post-traumatic state. These hypotheses will be tested in a three-phase study. In the first phase, acutely post-injury, subjects will undergo serial determinations of adrenocortical function to diagnose and treat acute adrenal insufficiency. Patients found to have inappropriately low cortisol levels, will be randomized to placebo or hydrocortisone therapy for 48 hours, and changes in blood pressure and vasopressor requirements will be monitored. Pituitary/hypothalamic MRIs will also be performed at 10 days and 6 months post-injury to assess for acute structural lesions and chronic pituitary volumetric changes. In the second phase, at 2 and 6 months post-injury, pituitary function tests will be performed. Hormone deficient patients will be placed on hormone replacement except for growth hormone (GH) after the 2-month time point. In the third phase, from 6 to 12 months post-injury, TBI patients with GH deficiency or GH insufficiency, who have memory impairment, concentration deficits, depression, anxiety or fatigue will be entered into a double-blind placebo-controlled GH replacement therapy trial to assess changes in these neurobehavioral and quality of life complaints. By diagnosing and treating both acute and chronic traumatic neuroendocrine deficiencies, this study may dramatically improve the lone-term prognosis of many TBI patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HYPOTHERMIA FOR ACUTE BRAIN INJURY IN CHILDREN Principal Investigator & Institution: Cox, Charles S.; Surgery; University of Texas Hlth Sci Ctr Houston Box 20036 Houston, Tx 77225 Timing: Fiscal Year 2003; Project Start 08-AUG-2003; Project End 31-JUL-2005 Summary: (provided by applicant): The Traumatic Brain Injury (TBI) Consortium at the University of Texas-Houston Medical School has a major commitment to multicenter clinical investigation. The PI, Charles Cox, M.D., is the Children's Fund for Pediatric Trauma Associate Professor of Surgery and Pediatrics and the Co-PI, Kevin Lally, M.D., the A.G. McNeese Professor and Chief of Pediatric Surgery. The TBI consortium has a track record for identifying and recruiting TBI patients for clinical studies across multiple points of care. The PI and Co-PI are board certified in both pediatric surgery and surgical critical care, which allows control of the acute care management of TBI patients. The group also includes a nationally recognized inpatient and outpatient rehabilitation center (The Institute for Rehabilitation and Research, TIRR). TIRR admits approximately 750 patients per year and has a 36-bed inpatient brain injury unit. TIRR also has a track record of NIH/NIDRR funded clinical research involving TBI patients. Post-rehabilitation outcomes follow-up is an established and mature component of the TBI component with outcome studies since 1982. Longitudinal studies of children with TBI are now in their 5th-9th year. UT-Houston provides: (A) A large patient population -

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Approximately 4,500 patients are admitted to the UT-Houston/Memorial Hermann Trauma Service per year (958 with a GCS of < 12), of which 1,400 are pediatric patients (167 with a GCS 20 mmHg) occurs in over 70% of severely head injured patients. Most of these patients suffer diffuse brain swelling, with the majority of the raised ICP in these patients being caused by vascular mechanisms (Marmarou et al. (1987) J. Neurosurg. 66:883-890). Web site: http://www.delphion.com/details?pn=US06046170__

Patent Applications on Traumatic Brain Injury As of December 2000, U.S. patent applications are open to public viewing.9 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to traumatic brain injury: •

2-Arachidonylglycerol (2-AG)-an inhibitor of tumor necrosis factor-alpha and neuroprotector of brain in closed head injury Inventor(s): Breuer, Aviva; (Jerusalem, IL), Gallily, Ruth; (Jerusalem, IL), Mechoulam, Raphael; (Jerusalem, IL), Panikashvili, David; (Jerusalem, IL), Shohami, Esther; (Mevasseret Zion, IL) Correspondence: Steinberg & Raskin, P.C.; 1140 Avenue OF The Americas, 15th Floor; New York; NY; 10036-5803; US Patent Application Number: 20020072539 Date filed: June 22, 2001 Abstract: The present invention relates to 2-arachidonylglycerol (2-AG) to be used as inhibitor of a tumor necrosis factor (TNF-.alpha.), in the reduction of edema caused by closed head injury, in the reduction of neurological deficits caused by closed head injury and stroke and in treating pathological conditions caused by TNF-.alpha. and/or by radical oxygen intermediates (ROI), in pharmaceutical composition for the same use comprising as active ingredient 2-AG. It comprises also the use of 2-AG and pharmaceutical compositions comprising same in the preparation of a medicament for the treatment of said indications and methods of treatment by 2-AG and pharmaceutical compositions comprising same for diseases caused by said indications. Excerpt(s): 1. The present invention relates to 2-arachidonylglycerol (2-AG) to be used as inhibitor of a tumor necrosis factor (TNF-.alpha.), in the reduction of edema caused by closed head injury, in the reduction of neurological deficits caused by closed head injury and stroke and in treating pathological conditions caused by TNF-.alpha. and/or by radical oxgen intermediates (ROI), in pharmaceutical composition for the same use comprising as active ingredient 2-AG, the use of 2-AG and pharmaceutical compositions comprising same in the preparation of a medicament for the treatment of said indications and methods of treatment by 2-AG and pharmaceutical compositions comprising same for diseases caused by said indications. 2. Two types of endogenous cannabinoids have been identified, the most thoroughly investigated compounds being

9

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

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arachidonylethanolamide (anandamide) and 2-arachidonylglycerol (2-AG) (Mechoulam and Ben-shabat, 1999). Although these endocannabinoids, in particular anandamide, have been the object of investigations in various systems, their physiological roles are not clear (Mechoulam et al., 1998). In view of the anti-inflammatory action of plant and synthetic cannabinoids, and of the presence of endocannabinoids and of cannabinoid receptors in organs associated with immune regulation, a plausible role attributed to the endocannabinoid system is an anti-inflammatory one. Indeed, anandamide has been shown to exhibit anti-inflammatory effects (Molina-Holgado et al., 1997) and 2-AG suppresses interleukin-2 through down regulation of the nuclear factor of activated T cells (Ouyang et al., 1998). 3. Tumor necrosis factor-.alpha. (TNF-.alpha.) is involved in the pathogenesis of various immune mediated processes and is the key mediator in septic shock (Tracey and Cerami 1993). This cytokine is released mainly by mononuclear phagocytic cells in response to injection of lipoplysaccharide (LPS, an endotoxin derived from Gram negative bacteria) to experimental animals. TNF-.alpha. affects both the central nervous system and periphery. It causes fever, sickness behavior, anorexia, symphathetic discharge and stimulation of pituitary hormones. It can also induce programmed cell death in neurons. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

3, 4-dihydroquinolin-2(1H)-one compounds as NR2B receptor antagonists Inventor(s): Kawamura, Mitsuhiro; (Aichi, JP) Correspondence: David R. Kurlandsky; Warner-lambert Company Llc; 2800 Plymouth Road; Ann Arbor; MI; 48105; US Patent Application Number: 20030216430 Date filed: April 14, 2003 Abstract: This invention provides a compound which is (R)-6-[2-[4-(3-fluorophenyl)-4- hydroxy-1-piperidinyl]-1-hydroxyethyl]-3,4-dihydro-2(1H)-quinolinone or a pharmaceutically acceptable ester of such compound, or a pharmaceutically acceptable salt thereof. The compound is useful for the treatment of disease conditions caused by overactivation of NMDA NR2B receptor such of pain, stroke, traumatic brain injury, Parkinson's disease, Alzheimer's disease, depression, anxiety, migraine, or the like in mammalian, especially humans. This invention also provides a pharmaceutical composition comprising the above compound. Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/375,939 filed Apr. 26, 2002. This invention relates to novel 3,4-dihydroquinolin2(1H)-one compounds. These compounds are useful as antagonists of NMDA (Nmethyl-D-aspartate) NR2B receptor, and are thus useful for the treatment of pain, stroke, traumatic brain injury, Parkinson's disease, Alzheimer's disease, depression, anxiety, migraine, or the like in mammalian, especially humans. The present invention also relates to a pharmaceutical composition comprising the above compounds. Glutamate plays dual role in the central nervous system (CNS) as essential amino acid and the principal excitatory neurotransmitters. There are at least four classes of receptors, specifically N-methyl-aspartate (NMDA), 2-amino-3-(methyl-3hydroxyisoxazol-4-yl)propionic acid (AMPA), kainate and metabotropic. There is considerable preclinical evidence that hyperalgesia and allodynia following peripheral tissue or nerve injury is not only due to an increase in the sensitivity of primary afferent nociceptors at the site of injury but also depends on NMDA receptor-mediated central changes in synaptic excitability. In humans, NMDA receptor antagonists have also been

Patents 167

found to decrease both pain perception and sensitization. Also, overactivation of NMDA receptor is a key event for triggering neuronal cell death under pathological conditions of acute and chronic forms of neurodegeneration. However, while NMDA receptor inhibition has therapeutic utility in the treatment of pain and neurodegenerative diseases, there are significant liabilities to many available NMDA receptor antagonists that can cause potentially serious side effects. NMDA subunits are differentially distributed in the CNS. Especially, NR2B is believed to be restricted to the forebrain and laminas I and II of the dosal horn. The more discrete distribution of NR2B subunit in the CNS may support a reduced side-effect profile of agents that act selectively at this site. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Administration of noncompetitive AMPA receptor antagonist for neuroprotection after traumatic brain injury Inventor(s): Belayev, Ludmila; (Miami, FL), Ginsburg, Myron D.; (Coconut Grove, FL) Correspondence: Ivax Corporation; 4400 Biscayne Boulevard; Miami; FL; 33137; US Patent Application Number: 20030073683 Date filed: September 18, 2002 Abstract: The invention provides compositions and methods for treating traumatic brain injury by the administration of a noncompetitive AMPA receptor antagonist. In certain embodiments, the noncompetitive AMPA receptor antagonist is a 2,3benzodiazepine derivative. Illustrative 2,3-benzodiazepine derivatives useful according to the invention include (R)-7-acetyl-5(4-aminophenyl)-8,9-dihydro-8-methyl-7H-1,3dioxolo[4,5-h][- 2,3]benzodiazepine. Excerpt(s): This application claims priority to United States Provisional Patent Application Serial No. 60/323,012, filed on Sep. 18, 2001. The present invention relates to the field.alpha.-amino-3-hydroxy-- 5-methyl-4-isoxazoic propionic acid (AMPA) receptor agonists. Traumatic brain injury ("TBI") represents one of the most tragic, common, and costly of all neurological disorders. Traumatic brain injury is associated with a large number of physical or behavioral disabilities. Each year in the United States, nearly 2 million people suffer from head injuries of sufficient severity to result in brain trauma (see Thurman et. al., J. Head Trauma Rehabil. 14: 602-615 (1999)). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Apparatus for simulating traumatic brain injury and method for inducing spinal cord injury Inventor(s): Eleftheriou, Evangelos; (Hoover, AL), Meythaler, Jay M.; (Birmingham, AL), Peduzzi-Nelson, Jean D.; (Chelsea, AL) Correspondence: Gifford, Krass, Groh, Sprinkle; Anderson & Citkowski, PC; 280 N Old Woodard Ave; Suite 400; Birmingham; MI; 48009; US Patent Application Number: 20040035433 Date filed: May 5, 2003 Abstract: This invention is an apparatus for simulating human traumatic injury in an animal, said apparatus comprising a support having an aperture having end walls and side walls disposed therein; a sliding element slidingly engaged with said side walls of

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said aperture, said sliding element having a retainer disposed thereon for receiving an animal holder having a hinged first end therein; and a crank arm operatively connected to both said sliding element, and an actuator mechanism. The apparatus allows animal head motion simulative of hyperflexural trauma associated with actual injuries. Excerpt(s): This application is a continuation-in-part of U.S. patent application Ser. No. 09/913,017 filed Sep. 28, 2001, which is the U.S. national phase of PCT Patent Application PCT/00/03182, which in turn claims priority of U.S. Provisional Patent Application Serial No. 60/118,986 filed Feb. 8, 1999. The subject invention relates to an apparatus and method for simulating human central nervous system injuries and, more particularly, the subject invention relates to an apparatus and method for animal simulation of human traumatic brain injury and spinal cord injury. The predominant mechanism in most cases of traumatic brain injury (TBI) is diffuse axonal injury (Whyte and Rosenthal, 1993). While axonal injury is common in all TBI regardless of severity (Povlishock et al., 1992; Mittl, 1994), a shearing of the axons occurs in human diffuse axonal injury (DAI) leading to progressive changes that ultimately may result in the loss of connections between nerve cells. The slow progression of events in DAI continues for up to several weeks after injury creating a window of opportunity small animal models for DAI which closely mimic the changes associated with DAI in humans (Maxwell et al., 1997; Povlishock, 1993). Without such a model to study the mechanism of injury, it is difficult to develop prevention and/or interventional methodologies to limit the extent of injury. In part, this may explain the lack of efficacy of the clinical trials to assess various medications to limit injury in TBI. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Aromatic and heteroaromatic substituted amides Inventor(s): Ballard, Theresa Maria; (Basle, CH), Hoffmann, Torsten; (Weil am Rhein, DE), Poli, Sonia Maria; (Basle, CH), Schnider, Patrick; (Oberwil, CH), Sleight, Andrew; (Riedisheim, FR) Correspondence: Hoffmann-la Roche INC.; Patent Law Department; 340 Kingsland Street; Nutley; NJ; 07110 Patent Application Number: 20030064983 Date filed: July 17, 2002 Abstract: The invention is the compounds2-(3,5-bis-trifluoromethyl-phenyl)-N-[6-(1,1dioxo-1.lambda.sup.6-thiomorpholin-4-yl)-4-o-tolyl-pyridin-3-yl]-N-methylisobutyramide and2-(3,5-bis-trifluoromethyl-phenyl)-N-[6-(1,1-dioxo-1.lambda.sup.6thiomor- pholin-4-yl)-4-(4-fluoro-2-methyl-phenyl)-pyridin-3-yl]-N-methyl-isobutyramide.Compounds of the invention are useful in pharmaceutical compositions for the treatment of migraine, rheumatoid arthritis, asthma, bronchial hyperreactivity, inflammatory bowel disease or for the treatment of disorders including Parkinson's disease, anxiety, depression, pain, headache, Alzheimer's disease, multiple sclerosis, edema, allergic rhinitis, Crohn's disease, ocular injury, ocular inflammatory diseases, psychosis, motion sickness, induced vomiting, emesis, urinary incontinence, psychoimmunologic or psychosomatic disorders, cancer, withdrawal symptoms of addictive drugs from opiates or nicotine, traumatic brain injury or benign prostatic hyperplasia. Excerpt(s): R.sup.1 is selected from the group consisting of hydrogen and fluoro. Compounds of formula 1, and pharmaceutically acceptable acid addition salts thereof,

Patents 169

have been shown to mediate the Neurokinin 1 (NK-1, substance P) receptor. The neuropeptide receptor for substance P (NK-1) is widely distributed throughout the mammalian nervous system (especially brain and spinal ganglia), the circulatory system and peripheral tissues (especially the duodenum and jejunum) and are involved in regulating a number of diverse biological processes. The receptor for substance P is a member of the superfamily of G protein-coupled receptors. The central and peripheral actions of the mammalian tachykinin substance P have been associated with numerous inflammatory conditions including migraine, rheumatoid arthritis, asthma, and inflammatory bowel disease as well as mediation of the emetic reflex and the modulation of central nervous system (CNS) disorders such as Parkinson's disease (Neurosci. Res., 1996, 7, 187-214), anxiety (Can. J. Phys., 1997, 75, 612-621) and depression (Science, 1998, 281, 1640-1645). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Bicyclic inhibitors of glycogen synthase kinase 3 Inventor(s): Nuss, John M.; (Danville, CA), Zhou, Xiaohui A.; (Berkeley, CA) Correspondence: Chiron Corporation; Intellectual Property - R440; P.O. Box 8097; Emeryville; CA; 94662-8097; US Patent Application Number: 20030008866 Date filed: August 26, 2002 Abstract: New bicyclic based compounds, compositions and methods of inhibiting the activity of glycogen synthase kinase (GSK3) in vitro and of treatment of GSK3 mediated disorders in vivo are provided. The methods, compounds and compositions of the invention may be employed alone, or in combination with other pharmacologically active agents in the treatment of disorders mediated by GSK3 activity, such as in the treatment of diabetes, Alzheimer's disease and other neurodegenerative disorders, obesity, atherosclerotic cardiovascular disease, essential hypertension, polycystic ovary syndrome, syndrome X, ischemia, traumatic brain injury, bipolar disorder, immunodeficiency or cancer. Excerpt(s): This application is a continuation of U.S. application Ser. No. 09/738,066 filed Dec. 15, 2000, and claims the benefit of U.S. Provisional Application No. 60/172,403, filed Dec. 17, 1999. This invention relates to new bicyclic compounds that inhibit the activity of glycogen synthase kinase 3 (GSK3), to pharmaceutical compositions containing the compounds and to the use of the compounds and compositions, alone or in combination with other pharmaceutically active agents. The compounds and compositions provided by the present invention have utility in the treatment of disorders mediated by GSK3 activity, such as diabetes, Alzheimer's disease and other neurodegenerative disorders, obesity, atherosclerotic cardiovascular disease, essential hypertension, polycystic ovary syndrome, syndrome X, ischemia, especially cerebral ischemia, traumatic brain injury, bipolar disorder, immunodeficiency and cancer. Glycogen synthase kinase 3 (GSK3) is a serine/threonine kinase for which two isoforms,.alpha. and.beta., have been identified. Woodgett, Trends Biochem. Sci., 16:17781 (1991). Both GSK3 isoforms are constitutively active in resting cells. GSK3 was originally identified as a kinase that inhibits glycogen synthase by direct phosphorylation. Upon insulin activation, GSK3 is inactivated, thereby allowing the activation of glycogen synthase and possibly other insulin-dependent events, such glucose transport. Subsequently, it has been shown that GSK3 activity is also inactivated by other growth factors that, like insulin, signal through receptor tyrosine kinases

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(RTKs). Examples of such signaling molecules include IGF-1 and EGF. Saito et al., Biochem. J., 303:27-31 (1994); Welsh et al., Biochem. J. 294:625-29 (1993); and Cross et al., Biochem. J., 303:21-26 (1994). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Co-administration of melanocortin receptor agonist and phosphodiesterase inhibitor for treatment of cyclic-AMP associated disorders Inventor(s): Carlson, Kenneth E.; (West Windsor, NJ), Macor, John E.; (Guilford, CT) Correspondence: Stephen B. Davis; Bristol-myers Squibb Company; Patent Department; P O Box 4000; Princeton; NJ; 08543-4000; US Patent Application Number: 20030069169 Date filed: March 4, 2002 Abstract: Co-administration of a melanocortin receptor agonist, particularly an MC-1R or MC-4R agonist, and a cAMP phosphodiesterase inhibitor is described for modulating levels of cyclic adenoise 3',5' monophosphate (cAMP) in a mammal. The inventive coadministration is useful in the treatment of diseases affected by activity of cAMP-PDE, including without limitation, inflammatory bowel disease, irritable bowel syndrome, rheumatoid arthritis, osteoarthritis, pancreatis, psoriasis, migraine, Alzheimer's Disease, Parkinson's disease, transplant rejection, asthma, acute respiratory distress syndrome, chronic obstructive pulmonary disease, stroke, and neurodegeneration of, and consequences of traumatic brain injury. Excerpt(s): This application claims the benefit of priority of U.S. applications Serial Nos. 60/273,206, and 60/273,291, filed Mar. 2, 2001, and U.S. Serial No. 60/289,719 filed May 9, 2001, the entire contents of which are incorporated herein by reference. The present invention relates to methods for treating diseases associated with intracellular levels of cAMP comprising co-administration of at least one compound that is a melanocortin receptor agonist and at least one compound that is a cAMP-PDE inhibitor, and to pharmaceutical compositions for practicing the claimed methods. Cyclic adenoise 3',5' monophosphate (cyclic AMP or cAMP) is a nucleotide messenger associated with inflammatory cell activity; it mediates the functional responses of cells to a multitide of hormones and neurotransmitters, including NF-.kappa.B. NF-.kappa.B is a pivotal component of the pro-inflammatory cascade, and its activation is a central event in initiating many inflammatory diseases. In a typical inflammatory response, NF-.kappa.B is activated in response to an inflammatory stimulus and once activated, induces expression of a wide array of pro-inflammatory genes. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Compounds with high monoamine transporter affinity Inventor(s): Blundell, Paul; (Winchester, MA), Madras, Bertha K.; (Newton, MA), Meltzer, Peter C.; (Lexington, MA), Wang, Pinglang; (Cambridge, MA) Correspondence: Edwards & Angell, Llp; P.O. Box 9169; Boston; MA; 02209; US Patent Application Number: 20040014992 Date filed: February 24, 2003

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Abstract: Featured compounds have high monoamine transport affinity and are characterized by one of the following two general formulas set out above. The compounds bind selectively or non-selectively to monoamine transporters. The compounds are useful to treat various medical indications including attention deficit hyperactivity disorder (ADHD), Parkinson's disease, cocaine addiction, smoking cessation, weight reduction, obsessive-compulsive disorder, various forms of depression, traumatic brain injury, stroke, and narcolepsy. Excerpt(s): This application is a continuation-in-part of U.S. application Ser. No. 09/691,396, a continuation-in-part of PCT Application No. PCT/US01/32575 having an international filing date of Oct. 17, 2001 and published in English under PCT Article 21(2) and a continuation-in-part of provisional application Serial No. 60/401,836, filed Aug. 6, 2002, the entire teachings of which are incorporated herein by reference. This invention relates to novel compositions with affinity for a monoamine transporter, such as the dopamine, norepinephrine, or serotonin transporter, in brain and in peripheral tissues. Monoamine transporters play a variety of roles, and compounds with affinity for the monoamine transporters have been proposed for therapy and/or diagnosis of medical indications that include (but are not limited to) attention deficit hyperactivity disorder (ADHD), Parkinson's disease, cocaine addiction, smoking cessation, weight reduction, obsessive-compulsive disorder, various forms of depression, traumatic brain injury, stroke, and narcolepsy. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Drugs for treatment of cerebral injury and methods of use thereof Inventor(s): Feustel, Paul J.; (Delmar, NY), Kimelberg, Harold K.; (Albany, NY) Correspondence: Mintz, Levin, Cohn, Ferris,; Glovsky And Popeo, P.C.; One Financial Center; Boston; MA; 02111; US Patent Application Number: 20030032676 Date filed: April 26, 2002 Abstract: Methods of treating stroke and conferring protection against cerebral injury in a subject following an ischemic event, wherein a tamoxifen compound is administered in an effective amount so as to confer protection on the population of cells. Treatable ischemic events include cerebrovascular disease or stroke, subarachnoid subhemorrhage, myocardial infarct, surgery and trauma. Excerpt(s): This application claims the benefit of priority under 35 U.S.C. 119(e) to copending U.S. Provisional Application No. 60/311,270, filed on Aug. 9, 2001; 60/332,128, filed on Nov. 21, 2001; and 60/362,287, filed on Mar. 7, 2002; the entire contents of which are incorporated herein by reference. Ischemia is an acute condition associated with an inadequate flow of oxygenated blood to a part of the body, caused by the constriction or blockage of the blood vessels supplying it. Ischemia occurs any time that blood flow to a tissue is reduced below a critical level. This reduction in blood flow can result from: (i) the blockage of a vessel by an embolus (blood clot); (ii) the blockage of a vessel due to atherosclerosis; (iii) the breakage of a blood vessel (a bleeding stroke); and (iv) the blockage of a blood vessel due to vasoconstriction such as occurs during vasospasms and possibly, during transient ischemic attacks (TIA) and following subarachnoid hemorrhage. Conditions in which ischemia occurs also include (i) myocardial infarction; (ii) trauma; and (iii) during cardiac and thoracic surgery and neurosurgery (blood flow needs to be reduced or stopped to achieve the aims of

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surgery). During myocardial infarct, heart stoppage or damage occurs which reduces blood flow to organs, and ischemia results. During various surgeries, blood flow reduction; clots; or air bubbles can lead to significant ischemic damage. When an ischemic event occurs, there is a gradation of injury that arises from the ischemic site. The cells at the site of blood flow restriction, undergo necrosis and form the core of a lesion. A penumbra is formed around the core where the injury is not immediately fatal but progresses slowly toward cell death. This progression to cell death may be reversed upon reestablishing blood flow (reperfusion) within a short time of the ischemic event. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Human N-type calcium channel isoform and uses thereof Inventor(s): Lipscombe, Diane; (Barrington, RI), Schorge, Stephanie; (Charvil, GB) Correspondence: Wolf Greenfield & Sacks, PC; Federal Reserve Plaza; 600 Atlantic Avenue; Boston; MA; 02210-2211; US Patent Application Number: 20020147309 Date filed: December 28, 2001 Abstract: The invention pertains to a human N-type calcium channel isoform, h.alpha.sub.1B+SFVG, which is involved in central nervous system signaling, and nucleic acids relating thereto. The present invention also includes fragments and biologically functional variants of the human h.alpha.sub.1B+sFvGchannel. Also included are human N-type calcium channel h.alpha.sub.1B+SFVG subunit inhibitors which inhibit human N-type calcium channel h.alpha.sub.1B+SFVG subunit activity by inhibiting the expression or function of human N-type calcium channel h.alpha.sub.1B+SFVG subunit. The invention further relates to methods of using such nucleic acids, polypeptides, and inhibitors in the treatment and/or diagnosis of disease, such as in methods for treating stroke, pain, e.g., neuropathic pain, and traumatic brain injury. Excerpt(s): This application is a divisional of U.S. application Ser. No. 09/268,163, filed Mar. 12, 1999, now pending, and claims the benefit under 35 U.S.C.sctn. 119(e) of U.S. provisional application serial No. 60/077,901, filed Mar. 13, 1998, the disclosures of which are incorporated by reference herein. The invention pertains to human N-type calcium channel.alpha.sub.1B subunit isoforms. Voltage gated calcium channels, also known as voltage dependent calcium channels (VDCCs) are multisubunit membrane spanning proteins which permit controlled calcium influx from an extracellular environment into the interior of a cell. Several types of voltage gated calcium channel have been described in different tissues, including N-type, P/Q-type, L-type and T-type channels. A voltage gated calcium channel permits entry into the cell of calcium upon depolarization of the membrane of the cell, which is a lessening of the difference in electrical potential between the outside and the inside of the cell. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Inhibitors of glycogen synthase kinase 3 Inventor(s): Boyce, Rustum S.; (San Francisco, CA), Desai, Manjo; (Pleasant Hill, CA), Harrison, Stephen D.; (Albany, CA), Johnson, Kirk; (Moraga, CA), Levine, Barry H.; (Lafayyette, CA), Nuss, John M.; (Danville, CA), Pfister, Keith B.; (San Ramon, CA), Ramurthy, Savithri; (Walnut Creek, CA), Ring, David B.; (Palo Alto, CA), Seely, Lynn; (Burlingame, CA), Wagman, Allan S.; (Oakland, CA) Correspondence: Christensen, O'connor, Johnson, Kindness, Pllc; 1420 Fifth Avenue; Suite 2800; Seattle; WA; 98101-2347; US Patent Application Number: 20020156087 Date filed: September 6, 2001 Abstract: New pyrimidine or pyridine based compounds, compositions and methods of inhibiting the activity of glycogen synthase kinase (GSK3) in vitro and of treatment of GSK3 mediated disorders in vivo are provided. The methods, compounds and compositions of the invention may be employed alone, or in combination with other pharmacologically active agents in the treatment of disorders mediated by GSK3 activity, such as diabetes, Alzheimer's disease and other neurodegenerative disorders, obesity, atherosclerotic cardiovascular disease, essential hypertension, polycystic ovary syndrome, syndrome X, ischemia, traumatic brain injury, bipolar disorder, immunodeficiency or cancer. Excerpt(s): This invention relates to new pyrimidine and pyridine derivatives that inhibit the activity of glycogen synthase kinase 3 (GSK3) and to pharmaceutical compositions containing the compounds and to the use of the compounds and compositions, alone or in combination with other pharmaceutically active agents. The compounds and compositions provided by the present invention have utility in the treatment of disorders mediated by GSK3 activity, such as diabetes, Alzheimer's disease and other neurodegenerative disorders, obesity, atherosclerotic cardiovascular disease, essential hypertension, polycystic ovary syndrome, syndrome X, ischemia, especially cerebral ischemia, traumatic brain injury, bipolar disorder, immunodeficiency and cancer. Glycogen synthase kinase 3 (GSK3) is a serine/threonine kinase for which two isoforms,.alpha. and.beta., have been identified. Woodgett, Trends Biochem. Sci., 16:17781 (1991). Both GSK3 isoforms are constitutively active in resting cells. GSK3 was originally identified as a kinase that inhibits glycogen synthase by direct phosphorylation. Upon insulin activation, GSK3 is inactivated, thereby allowing the activation of glycogen synthase and possibly other insulin-dependent events, such glucose transport. Subsequently, it has been shown that GSK3 activity is also inactivated by other growth factors that, like insulin, signal through receptor tyrosine kinases (RTKs). Examples of such signaling molecules include IGF-1 and EGF. Saito et al., Biochem. J., 303:27-31 (1994); Welsh et al., Biochem. J. 294:625-29 (1993); and Cross et al., Biochem. J, 303:21-26 (1994). Agents that inhibit GSK3 activity are useful in the treatment of disorders that are mediated by GSK3 activity. In addition, inhibition of GSK3 mimics the activation of growth factor signaling pathways and consequently GSK3 inhibitors are useful in the treatment of diseases in which such pathways are insufficiently active. Examples of diseases that can be treated with GSK3 inhibitors are described below. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Method and apparatus for a head injury simulation system Inventor(s): Mota, Alejandro; (Pasadena, CA), Ortiz, Michael; (La Canada, CA) Correspondence: J.D. Harriman II; Coudert Brothers Llp; 23rd Floor; 333 South Hope Street; Los Angeles; CA; 90071; US Patent Application Number: 20030074172 Date filed: February 6, 2002 Abstract: The present invention relates to a head injury simulation system; specifically, the ballistic penetration of the skull by a projectile. In one or more embodiments of the present invention, the cohesive theories of fracture, in conjunction with the explicit simulation of fracture and fragmentation, is applied to finite element simulations of firearm injuries to the human cranium. The simulation explicitly reproduces the impact, the nucleation of fracture, the extension of damage, and the scattering of comminuted fragments. In one embodiment, the bullet-skull impact is obtained with an approximated version of a nonsmooth contact algorithm. In one embodiment, the explicit simulation of fracture nucleation and propagation is achieved by a self-adaptive fragmentation procedure. In one embodiment, the progressive decohesion of fractures is modeled by cohesive elements. Excerpt(s): Applicant hereby claims priority to provisional patent application 60/266,606 filed Feb. 6, 2001. The present invention relates to the field of computational modeling of physical processes. Specifically, the present invention relates to a method and apparatus for the simulation of a head injury by a projectile. In the U.S., almost one million people suffer from the effects of head injuries every year. More than 400,000 patients with new injuries of the head are admitted to U.S. hospitals each year. Many of these injuries result from firearm-related incidents. Since the late 1950's, firearm deaths have increased dramatically in the United States. In 1988, for example, firearm-related incidents were responsible for 34,000 deaths, making them the eighth leading cause of death in the U.S. Moreover, for every firearm-related death, there are an additional seven people who sustain non fatal gunshot wounds. Gunshot wounds to the head are the leading or second leading cause of head injury in many U.S. cities. They are also the most lethal of all firearm injuries. It is estimated that gunshot wounds to the head have a greater than 90% fatality rate for U.S. civilians, and at least two thirds of the victims die before reaching a hospital. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Method for diagnosing and distinguishing traumatic brain injury and diagnostic devices for use therein Inventor(s): Davey, Michelle; (Mississauga, CA), Jackowski, George; (Kettleby, CA), Stanton, Eric B.; (Burlington, CA), Takahashi, Miyoko; (North York, CA) Correspondence: Mchale & Slavin; 4440 Pga Blvd; Suite 402; Palm Beach Gardens; FL; 33410 Patent Application Number: 20030040660 Date filed: August 27, 2001 Abstract: Methods of implementing rapid assessment of patients presenting with brain trauma injury in humans are provided. These methods comprise presenting a subject possibly suffering from traumatic brain injury, selecting one or more markers to detect

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injury, tracking evolution of injury by tracking marker concentration over time, and determining repetitive injury by the correlation of molecular weight markers appearing over the course of time. Excerpt(s): The present invention relates to methods for rapid assessment of subjects suffering from traumatic brain injury. The invention particularly relates to a process and device for one or more markers indicative of cellular damage, and further relates to tracking the concentration of those markers to accurately assess severity of injury. The present invention additionally relates to the diagnosis of repeated injury associated with traumatic brain injury. Damage to the brain by a physical force is broadly termed traumatic brain injury (TBI) The resulting effect of TBI causes alteration of normal brain processes attributable to changes in brain structure and/or function. There are two basic types of brain injury, open head injury and closed head injury. In an open head injury, an object, such as a bullet, penetrates the skull and damages the brain tissue. Closed head injury is usually caused by a rapid movement of the head during which the brain is whipped back and forth, bouncing off the inside of the skull. Closed head injuries are the most common of the two, which often results from motor vehicle crashes or falls. In a closed head injury, brute force or forceful shaking injures the brain. The stress of this rapid movement pulls apart and stretches nerve fibers or axons, breaking connections between different parts of the brain. In most cases, a resulting blood clot, or hematoma, may push on the brain or around it, raising the pressure inside the head. Both open and closed head injuries can cause severe damage to the brain, resulting in the need for immediate medical attention. Depending on the type of force that hits the head, varying injuries such as any of the following can result: jarring of the brain within the skull, concussion, skull fracture, contusion, subdural hematoma, or diffuse axonal injury. Though each person's experience is different, there are common problems that many people with TBI face. Possibilities documented include difficulty in concentrating, ineffective problem solving, short and long-term memory problems, and impaired motor or sensory skills; to the point of an inability to perform daily living skills independently such as eating, dressing, or bathing. The most widely accepted concept of brain injury divides the process into primary and secondary events. Primary brain injury is considered to be more or less complete at the time of impact, while secondary injury evolves over a period of hours to days following trauma. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method for using tethered bis(polyhydroxyphenyls) and O-alkyl derivatives thereof in treating inflammatory conditions of the central nervous system Inventor(s): Floyd, Robert A.; (Oklahoma City, OK), Hensley, Kenneth; (Oklahoma City, OK) Correspondence: Fulbright & Jaworski L.L.P.; 600 Congress AVE.; Suite 2400; Austin; TX; 78701; US Patent Application Number: 20040014721 Date filed: June 5, 2003 Abstract: The present invention involves the use of tethered bis(polyhydroxyphenyl) compounds to slow the progression of neurological diseases in which pro-inflammatory cytokine stimulation of microglial cells is reasonably anticipated to make a significant contribution to disease pathology. Diseases for which this is the case include amyotrophic lateral sclerosis (ALS) and other motor neuron diseases (MNDs) of similar clinical presentation; Parkinson's disease (PD); Alzheimer's disease (AD); spino-bulbar

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atrophy; (SBA); Huntington's disease (HD); myasthenia gravis (MG); multiple sclerosis (MS); HIV-associated dementia; fronto-temporal dementia (FTD); stroke; encephalomyelitis; traumatic brain injury; age-related retinal degeneration; and other neurological diseases possessing microglial activation as a contributing pathological feature. Specific examples are presented where the tethered bis(polyhydroxyphenyl) compound is resveratrol; piceatannol; nordihydroguaiaretic acid (NDGA); curcumin, or sesamin. Excerpt(s): The present application claims priority to co-pending U.S. Provisional Patent Application Serial No. 60/387,374 filed on Jun. 10, 2002. The entire text of the abovereferenced disclosure is specifically incorporated herein by reference without disclaimer. The present invention relates generally to the fields of pharmacology and immunological pharmacotherapy. More particularly, it concerns methods for treating neurological diseases, including but not limited to neurological diseases exhibiting microglial activation as a contributing pathological feature. The present invention also concerns methods of treating other diseases such as inflammatory diseases and benign or malignant hyperplasias that involve components of pro-inflammatory cytokine action on macrophage-like cells. Most or all neurological diseases share a common pathological feature: the activation of microglia, which are specialized myeloid (macrophage-like) cells in the central nervous system (CNS). For example, HLA-DR reactive microglia proliferate in regions of the Alzheimer's-diseased (AD) brain most dramatically affected by histopathological hallmarks of the disease (Wisniewski et al., 1990; Hensley et al., 1995). Similar microglial proliferation is observed in the spinal cord of patients with ALS (amyotrophic lateral sclerosis) (Hall et al., 1998; Alexianu et al., 2001); in the diseased Parkinsonian brain (Vila et al., 2001); in the brains of patients with HIV (Kaul et al., 2001); and in post-traumatic or post-ischemic brain tissue (Floyd et al., 2000). Thus, microglial responsitivity is common to most, if not all, neurodegenerative conditions. Some microglial functions are beneficial, for instance, in the clearing of apoptotic cells and the resolution of injury. Exacerbated or chronic microglial activation, on the other hand, can damage neurons through direct and indirect action involving overproduction of reactive oxygen and reactive nitrogen species (ROS and RNS), and the propagation of inflammatory cytokine cascades. When activated, microglia synthesize potential neurotoxins such as reactive oxygen species (ROS, including but not restricted to oxygen-centered free radicals); reactive nitrogen species (RNS, including but not restricted to nitric oxide and derived nitrogen oxides); and pro-inflammatory cytokines (including but not restricted to interleukin 1 (IL1.alpha. and IL1.beta.), interferon gamma (IFN.gamma.) and tumor necrosis factor alpha (TNF.alpha.) (Colton et al., 1994; Meda et al., 1995). In most cases, it is not clear exactly why microglia become activated, and few strategies have been proposed and tested that offer a clear means by which to suppress the conversion of microglia from an innocuous quiescent phenotype to an active and potentially neurotoxic phenotype. The development of such means would require discovery or invention and validation of small molecules that could inhibit microglial activation caused by multiple stimuli including exposure to proinflammatory cytokines (especially IL1.beta. and TNF.alpha.) as well as immunoglobulins (especially IgG and autoantigen complexes). Such molecules would have to be permeable across the blood brain barrier to a degree that would allow CNS accumulation of the active compounds in sufficient concentration for bioactivity; and they would have to be essentially nontoxic to neurons and peripheral tissues. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Method of modulating microglial activation for the treatment of acute and chronic neurodegenerative disorders Inventor(s): Parvathenani, Lav Kumar; (Rocky Hill, CT), Posmantur, Rand M.; (Branford, CT) Correspondence: Marla J Mathias; Bristol-myers Squibb Company; Patent Department; P O Box 4000; Princeton; NJ; 08543-4000; US Patent Application Number: 20020022650 Date filed: July 5, 2001 Abstract: The present invention provides methods of modulating or inhibiting microglia activation comprising the administration of a compound capable of inhibiting 5-LOX, FLAP, attenuating degradation of I.kappa.B.alpha. or inhibiting nuclear translocation of the NF-.kappa.B active complex for the treatment of Alzheimer's disease, brain ischemia, traumatic brain injury, Parkinson's Disease, Multiple Sclerosis, ALS, subarachnoid hemorrhage or other disorders associated with excessive production of inflammatory mediators in the brain. Excerpt(s): This non-provisional application claims priority from provisional applications U.S. Ser. No. 60/218,085 filed Jul. 13, 2000 and U.S. Ser. No. 60/261,332 filed Jan. 12, 2001. The present invention comprises methods of treating various acute and chronic central nervous system disorders by the administration of FLAP or 5lipoxygenase inhibitors. Acute and chronic brain injuries can activate resident microglia (resident macrophage-like cells found in the central nervous system) as well as recruit peripheral immune cells to injured brain regions that can exacerbate neuronal damage. Inflammatory processes can induce cell death by (a) the release of proteases and free radicals that induce lipid peroxidation, (b) direct cytotoxic effects or (c) by the phagocytosis of sublethally injured neurons. The attenuation of microglia and peripheral immune cell activation has been correlated with significant neuronal protection in pre-clinical studies of ischemia, traumatic brain injury, spinal cord injury and Alzheimer's disease. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Method of treating of demyelinating diseases or conditions Inventor(s): Petty, Margaret; (Bridgewater, NJ), Rampe, David; (Bernardsville, NJ), Rathbone, Michel P.; (Hamilton, CA), Smith, Craig P.; (Hillsborough, NJ) Correspondence: Ross J. Oehler; Aventis Pharmaceuticals INC.; Route 202-206, Mail Code: D-303a; Bridgewater; PA; 08807; US Patent Application Number: 20030105150 Date filed: February 14, 2002 Abstract: N-(Pyridinyl)-1H-indol-1-amines of formula I provide a unique combination of blocking properties for both the potassium and sodium channels. These compounds are useful for the treatment of Demyelinating Diseases and Conditions such as Multiple Sclerosis, Spinal Cord Injury, Traumatic Brain Injury and Stroke. The compounds are also useful for Stroke Rehabilitation, the treatment of Bladder Irritation and Dysfunction, and the treatment of Neuropathic Pain and Chemokine-Induced Pain. Excerpt(s): Multiple sclerosis (MS) is a degenerative and inflammatory neurological disease that affects the central nervous system, and is associated with formation of

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neuronal plaques and impaired neuronal conduction due to demyelination (loss of myelin). Similarly, extensive demyelination is commonly reported in spinal cord trauma and stroke (Bunge et al, 1993; Blight and DeCrescito, 1986; Pendlebury et al, 2000). Basic research into the physiology of the action potential propagation in myelinated fibers showed that conduction block in demyelinated fibers was partly due to the appearance of aminopyridine-sensitive potassium channels in areas of myelin loss (Bever 1996). Action potentials propagate along normal myelinated nerve fibers by a process of salutatory conduction, which results from a sodium current generated by the opening of voltage-sensitive sodium channels at the node of Ranvier. Thus, at the onset of electrical stimulation, sodium (Na.sup.+) ions enter the neuron, causing the neuron to become more positively charged. When the positive nature of the neuron approaches a critical level, "depolarization" occurs. Depolarization allows a positive core of ions to flow down the neuron, along the axon and to the nerve ending. For the neuron to "reset" itself, the excess positive charge must be dissipated. This is done via the outflow of potassium ions (hereinafter "K+") through potassium channels. When myelin is disrupted, voltage-sensitive potassium channels that open during depolarization appear on the axolemma. The potassium current, flowing opposite to the sodium current, decreases action potential amplitude and duration, contributing to conduction failure by decreasing the distal effective current densities. These conduction deficits are associated with disabling symptoms, including muscle weakness. By blocking the outflow of K.sup.+ through potassium channels, the neuron remains depolarized longer and is more easily restimulated. Thus, potassium channel blockers are believed to be useful in the treatment of diseases and conditions which impair action potential transmission such as MS, Traumatic Brain Injury (hereinafter "TBI") and Spinal Cord Injury (hereinafter "SCI"). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

METHOD OF TREATING, PREVENTING OR INHIBITING CENTRAL NERVOUS SYSTEM INJURIES AND DISEASES Inventor(s): Koenig, Michael L.; (Silver Spring, MD), Meyerhoff, James L.; (Silver Spring, MD), Yourick, Debra L.; (Linthicum Heights, MD) Correspondence: Office OF The Staff Judge Advocate; U.S. Army Medical Research And Materiel Command; Attn: Mcmr-ja (MS. Elizabeth Arwine); 504 Scott Street; Fort Detrick; MD; 21702-5012; US Patent Application Number: 20020177558 Date filed: April 20, 2001 Abstract: Methods of preventing, treating, or both preventing and treating CNS injury, disease, neurotoxicity or memory deficit in a subject by the administration of at least one lipoic acid compound to the subject are disclosed. Examples of CNS injuries or disease include traumatic brain injury (TBI), posttraumatic epilepsy (PTE), stroke, cerebral ischemia, neurodegenerative diseases of the brain such as Parkinson's disease, Dementia Pugilistica, Huntington's disease and Alzheimer's disease, brain injuries secondary to seizures which are induced by radiation, exposure to ionizing or iron plasma, nerve agents, cyanide, toxic concentrations of oxygen, neurotoxicity due to CNS malaria or treatment with anti-malaria agents, and other CNS traumas. Examples of lipoic acid compounds include alpha-lipoic acid (ALA), dihydrolipoic acid (DHLA), 2-(N,Ndimethylamine) ethylamido lipoate-HCL (LA-plus), the oxidized or reduced R- or Sisomers thereof, the metabolites of alpha-lipoic acid such as 6,8-bisnorlipoic acid and

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tetranorlipoic acid and analogs thereof. Also disclosed are pharmaceutical compositions and kits comprising at least one lipoic acid compound. Excerpt(s): This application claims the benefit of U.S. Provisional Patent Application No. 60/198,958, filed Apr. 21, 2000, naming James L. Meyerhoff, Debra L. Yourick and Michael L. Koenig as inventors, which is herein incorporated by reference. 1. Field of the Invention. The invention relates to a method of treating, preventing or inhibiting central nervous system (CNS) injuries and diseases. In particular, the invention relates to a method of treating, preventing or inhibiting a CNS injury or disease in a subject by the administration of at least one lipoic acid compound to the subject. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Methods for modulating the axonal outgrowth of central nervous system neurons Inventor(s): Benowitz, Larry I.; (Newton Centre, MA) Correspondence: David S. Resnick; Nixon Peabody Llp; 101 Federal Street; Boston; MA; 02110; US Patent Application Number: 20020042390 Date filed: November 29, 2001 Abstract: Methods for modulating the axonal outgrowth of central nervous system neurons are provided. Methods for stimulating the axonal outgrowth of central nervous system neurons following an injury (e.g., stroke, Traumatic Brain Injury, cerebral aneurism, spinal cord injury and the like) and methods for inhibiting the axonal outgrowth of central nervous system neurons are also provided. Finally, a packed formulation comprising a pharmaceutical composition comprising an inosine nucleoside and a pharmaceutically acceptable carrier packed with instructions for use of the pharmaceutical composition for treatment of a central nervous system disorder is provided. Excerpt(s): Past early childhood, injury to the central nervous system (CNS) results in functional impairments that are largely irreversible. Within the brain or spinal cord, damage resulting from stroke, trauma, or other causes can result in life-long losses in cognitive, sensory and motor functions, and even maintenance of vital functions. Nerve cells that are lost are not replaced, and those that are spared are generally unable to regrow severed connections, although a limited amount of local synaptic reorganization can occur close to the site of injury. Functions that are lost are currently untreatable. Regenerative failure in the CNS has been attributed to a number of factors, which include the presence of inhibitory molecules on the surface of glial cells that suppress axonal growth; absence of appropriate substrate molecules such as laminin to foster growth and an absence of the appropriate trophic factors needed to activate programs of gene expression required for cell survival and differentiation. By contrast, within the peripheral nervous system (PNS), injured nerve fibers can regrow over long distances, with eventual excellent recovery of function. Within the past 15 years, neuroscientists have come to realize that this is not a consequence of intrinsic differences between the nerve cells of the peripheral and central nervous system; remarkably, neurons of the CNS will extend their axons over great distances if given the opportunity to grow through a grafted segment of PNS (e.g., sciatic nerve). Therefore, neurons of the CNS retain a capacity to grow if given the right signals from the extracellular environment. Factors which contribute to the differing growth potentials of the CNS and PNS include partially characterized, growth-inhibiting molecules on the surface of the

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oligodendrocytes that surround nerve fibers in the CNS, but which are less abundant in the comparable cell population of the PNS (Schwann cells); molecules of the basal laminin and other surfaces that foster growth in the PNS but which are absent in the CNS (e.g., laminin); and trophic factors, soluble polypeptides which activate programs of gene expression that underlie cell survival and differentiation. Although such trophic factors are regarded as essential for maintaining the viability and differentiation of nerve cells, the particular ones that are responsible for inducing axonal regeneration in the CNS remain uncertain. As a result, to date, effective treatments for CNS injuries have not been developed. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Methods for treating cognitive impairments caused by traumatic brain injuries 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: 20020035129 Date filed: September 4, 2001 Abstract: The invention describes novel methods for treating and preventing cognitive impairments caused by traumatic brain injuries 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. Excerpt(s): This application claims priority to 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. 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. 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

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Methods for treating neurological injuries and disorders Inventor(s): Ebendal, Ted; (Uppsala, SE), Jarpe, Michael; (Marlborough, MA), Marchionni, Mark; (Arlington, MA) Correspondence: Dike, Bronstein, Roberts & Cushman; Intellectual Property Practice Group; Edwards & Angell, Llp; P.O. Box 9169; Boston; MA; 02209; US Patent Application Number: 20030069176 Date filed: January 8, 2001 Abstract: The present invention relates to methods for treatment of nerve cell death (degeneration) and neurodegenerative diseases. Methods of the invention include administering, an effective amount of GDF-1 alone or in combination with

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neurotrophin-3, to a patient in need of such treatment such as a person suffering from stroke or traumatic brain injury or a neurodegenerative disease. Excerpt(s): The present application claims the benefit of U.S. provisional application No. 60/091,791, filed Jul. 6, 1998, which is incorporated herein by reference in its entirety. The present invention relates to methods for treatment of neurological injuries and neurodegenerative disorders. More particularly, in one aspect, the invention includes methods of use of the polypeptide GDF-1, or a fragment or derivative of GDF-1, or a nucleic acid encoding GDF-1, to treat a subject suffering from or susceptible to a neurological injury or neurodegenerative disease. The invention also provides methods for treatment of neurological injury and neurodegenerative disease with a combination of GDF-1 that comprise administration of a combination of GDF-1 and neurotrophin-3 (NT-3). Nerve cell death (degeneration) can cause potentially devastating and irreversible effects for an individual and may occur e.g. as a result of stroke, heart attack or other brain or spinal chord ischemia or trauma. Additionally, neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, Amyotrophic Lateral Sclerosis, Down's Syndrome and Korsakoff's disease, involve nerve cell death (degeneration). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

NMDA receptor agonist pharmaceutical compositions Inventor(s): Hong, Jinyang; (Stonington, CT), Kim, Yesook; (Branford, CT) Correspondence: Gregg C. Benson; Pfizer INC.; Patent Department, MS 4159; Eastern Point Road; Groton; CT; 06340; US Patent Application Number: 20020111366 Date filed: December 5, 2001 Abstract: This invention relates to stable pharmaceutical compositions of the NMDA receptor agonist, (1S,2S)-1-(4-hydroxyphenyl)-2-(4-hydroxy-4-phenylpiperidin-1-yl)-1propanol], methods of preparing such pharmaceutical compositions and methods of treating stroke, spinal cord trauma, traumatic brain injury, multiinfarct dementia, CNS degenerative diseases such as Alzheimer's disease, senile dementia of the Alzheimer's type, Huntington's disease, Parkinson's disease, epilepsy, amyotrophic lateral sclerosis, pain, AIDS dementia, psychotic conditions, drug addictions, migraine, hypoglycemia, anxiolytic conditions, urinary incontinence and an ischemic event arising from CNS surgery, open heart surgery or any procedure during which the function of the cardiovascular system is compromised using the pharmaceutical compositions. Excerpt(s): This invention provides stable pharmaceutical compositions of the Nmethyl-D-aspartic acid (NMDA) receptor antagonist, (1S,2S)-1-(4-hydroxyphenyl)-2-(4hydroxy-4-phenylpiperidin-1-yl)-1-propanol, methods of preparing such pharmaceutical compositions and methods of treating stroke, spinal cord trauma, traumatic brain injury, multiinfarct dementia, CNS degenerative diseases such as Alzheimer's disease, senile dementia of the Alzheimer's type, Huntington's disease, Parkinson's disease, epilepsy, amyotrophic lateral sclerosis, pain, AIDS dementia, psychotic conditions, drug addictions, migraine, hypoglycemia, anxiolytic conditions, urinary incontinence and an ischemic event arising from CNS surgery, open heart surgery or any procedure during which the function of the cardiovascular system is compromised, using the pharmaceutical compositions of this invention. (1S,2S)-1-(4Hydroxyphenyl)-2-(4-hydroxy-- 4-phenylpiperidin-1-yl)-1-propanol (hereafter referred

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to as the "Compound") is a neuroprotecting agent that is useful for the treatment of stroke, spinal cord trauma, traumatic brain injury, multiinfarct dementia, CNS degenerative diseases such as Alzheimer's disease, senile dementia of the Alzheimer's type, Huntington's disease, Parkinson's disease, epilepsy, amyotrophic lateral sclerosis, pain, AIDS dementia, psychotic conditions, drug addictions, migraine, hypoglycemia, anxiolytic conditions, urinary incontinence and an ischemic event arising from CNS surgery, open heart surgery or any procedure during which the function of the cardiovascular system is compromised. The Compound exhibits activity as an NMDA receptor antagonist. NMDA is an excitatory amino acid involved in excitatory neurotransmission in the central nervous system. NMDA antagonists are compounds that block the NMDA receptor by interacting with the receptor's binding site. Antagonists of neurotransmission at NMDA receptors are useful therapeutic agents for the treatment of neurological disorders. U.S. Pat. No. 4,902,695 is directed to series of competitive NMDA antagonists useful for the treatment of neurological disorders, including epilepsy, stroke, anxiety, cerebral ischemia, muscular spasms, and neurodegenerative disorders such as Alzheimer's disease and Huntington's disease. U.S. Pat. No. 4,968,878 is directed to a second series of competitive NMDA receptor antagonists useful for the treatment of similar neurological disorders and neurodegenerative disorders. U.S. Pat. No. 5,192,751 discloses a method of treating urinary incontinence in a mammal, which comprises administering an effective amount of a competitive NMDA antagonist. Commonly assigned U.S. Pat. No. 5,272,160 and commonly assigned U.S. Pat. No. 5,710,168 (the disclosures of which are hereby incorporated by reference) disclose the Compound and methods of using the Compound for treatment of diseases or conditions that are susceptible to treatment by blocking NMDA receptor sites, including stroke, spinal cord trauma, traumatic brain injury, multiinfarct dementia, CNS degenerative diseases, epilepsy, amyotrophic lateral sclerosis, pain, AIDS dementia, psychotic conditions, drug addictions, migraine, hypoglycemia, anxiolytic conditions, urinary incontinence and ischemic events. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Pharmaceutical combinations for the treatment of stroke and traumatic brain injury Inventor(s): Chenard, Bertrand L.; (Waterford, CT), Menniti, Frank S.; (Mystic, CT), Saltarelli, Mario D.; (Mystic, CT) Correspondence: Pfizer Inc; 150 East 42nd Street; 5th Floor - Stop 49; New York; NY; 10017-5612; US Patent Application Number: 20020045656 Date filed: September 6, 2001 Abstract: This invention relates to methods of treating traumatic brain injury (TBI) or hypoxic or ischemic stroke, comprising administering to a patient in need of such treatment an NR2B subtype selective N-methyl-D-aspartate (NMDA) receptor antagonist in combination with either: (a) a neutrophil inhibitory factor (NIF); (b) a sodium channel antagonist; (c) a nitric oxide synthase (NOS) inhibitor; (d) a glycine site antagonist; (e) a potassium channel opener; (f) an AMPA/kainate receptor antagonist; (g) a calcium channel antagonist; (h) a GABA-A receptor modulator (e.g., a GABA-A receptor agonist); or (i) an antiinflammatory agent. Excerpt(s): This application claims priority under 35 U.S.C. 119(e) of U.S. Provisional Application No. 60/230,944, filed Sep. 6, 2000. This invention relates to methods of treating traumatic brain injury (TBI), ischemic stroke, or hypoxic brain injury,

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comprising administering to a patient in need of such treatment an NR2B subtype selective N-methyl-D-aspartate (NMDA) receptor antagonist in combination with one or more other compounds that protect neurons from toxic insult, inhibit the inflammatory reaction after brain damage or promote cerebral reperfusion. More specifically, this invention relates to methods of treating traumatic brain injury (TBI) or hypoxic or ischemic stroke, comprising administering to a patient in need of such treatment an NR2B subtype selective N-methyl-D-aspartate (NMDA) receptor antagonist in combination with either: (a) a neutrophil inhibitory factor (NIF); (b) a sodium channel antagonist; (c) a nitric oxide synthase (NOS) inhibitor; (d) a glycine site antagonist; (e) a potassium channel opener; (f) an AMPA/kainate receptor antagonist; (g) a calcium channel antagonist; (h) a GABA-A receptor modulator (e.g., a GABA-A receptor agonist); (i) an antiinflammatory agent; or (j) a matrix metalloprotease (MMP) inhibitor. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Potassium channel blocking agents Inventor(s): Jensen, Bo Skaaning; (Copenhagen S, DK), Olesen, Soren Peter; (Klampenborg, DK), Peters, Dan; (Arlov, SE), Strobaek, Dorte; (Farum, DK), Teuber, Lene; (Vaerlose, DK) Correspondence: Birch Stewart Kolasch & Birch; PO Box 747; Falls Church; VA; 220400747; US Patent Application Number: 20020049246 Date filed: December 29, 2000 Abstract: This invention relates to novel potassium channel blocking agents, and their use in the preparation of pharmaceutical compositions.Moreover the invention is directed to pharmaceutical compositions useful for the treatment or alleviation of diseases or disorders associated with the activity of potassium channels, in particular asthma, cystic fibrosis, chronic obstructive pulmonary disease and rhinorrhea, convulsions, vascular spasms, coronary artery spasms, renal disorders, polycystic kidney disease, bladder spasms, urinary incontinence, bladder outflow obstruction, irritable bowel syndrome, gastrointestinal dysfunction, secretory diarrhoea, ischaemia, cerebral ischaemia, ischaemic hearth disease, angina pectoris, coronary hearth disease, traumatic brain injury, psychosis, anxiety, depression, dementia, memory and attention deficits, Alzheimer's disease, dysmenorrhea, narcolepsy, Reynaud's disease, intermittent claudication, Sjorgren's syndrome, migraine, arrhythmia, hypertension, absence seizures, myotonic muscle dystrophia, xerostomi, diabetes type II, hyperinsulinemia, premature labor, baldness, cancer, and immune suppression. Excerpt(s): This invention relates to novel potassium channel blocking agents, and their use in the preparation of pharmaceutical compositions. Moreover the invention is directed to pharmaceutical compositions useful for the treatment or alleviation of diseases or disorders associated with the activity of potassium channels, in particular asthma, cystic fibrosis, chronic obstructive pulmonary disease and rhinorrhea, convulsions, vascular spasms, coronary artery spasms, renal disorders, polycystic kidney disease, bladder spasms, urinary incontinence, bladder outflow obstruction, irritable bowel syndrome, gastrointestinal dysfunction, secretory diarrhoea, ischaemia, cerebral ischaemia, ischaemic hearth disease, angina pectoris, coronary hearth disease, traumatic brain injury, psychosis, anxiety, depression, dementia, memory and attention deficits, Alzheimer's disease, dysmenorrhea, narcolepsy, Reynaud's disease, intermittent claudication, Sjorgren's syndrome, migraine, arrhythmia, hypertension, absence

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seizures, myotonic muscle dystrophia, xerostomi, diabetes type II, hyperinsulinemia, premature labor, baldness, cancer, and immune suppression. Ion channels are transmembrane proteins, which catalyze the transport of inorganic ions across cell membranes. The ion channels participate in processes as diverse as the generation and timing of action potentials, synaptic transmissions, secretion of hormones, contraction of muscles, etc. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Prodrug of an ice inhibitor Inventor(s): Davies, Robert; (Arlington, MA), Wannamaker, Marion W.; (Stow, MA) Correspondence: Vertex Pharmaceuticals INC.; 130 Waverly Street; Cambridge; MA; 02139-4242; US Patent Application Number: 20020013278 Date filed: May 18, 2001 Abstract: This invention describes an ICE inhibitor prodrug (I) having good bioavailability. 1Compound I is useful for treating IL-1 mediated diseases such as rheumatoid arthritis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, inflammatory peritonitis, septic shock, pancreatitis, traumatic brain injury, organ transplant rejection, osteoarthritis, asthma, psoriasis, Alzheimer's disease, myocardial infarction, congestive heart failure, Huntington's disease, atherosclerosis, atopic dermatitis, leukemias and related disorders, myelodysplastic syndrome, uveitis or multiple myeloma. Excerpt(s): Pursuant to Title 35, United States Code,.delta. 119 this application claims benefit of U.S. Provisional Application Serial No. 60/205,439, filed May 19, 2000. The present invention relates to a novel interleukin-1.beta. converting enzyme (ICE) inhibitor in its prodrug form. The compound and pharmaceutical compositions thereof are useful as agents to treat interleukin-1-(IL-1), apoptosis-, interferon-.gamma. inducing factor-(IL-18), or interferon-.gamma. (IFN-.gamma.) mediated diseases, including inflammatory diseases, autoimmune diseases, destructive bone disorders, proliferative disorders, infectious diseases, and degenerative diseases. This invention also relates to methods for inhibiting ICE activity and decreasing IL-18 production and IFN-.gamma. production and methods for treating interleukin-1, apoptosis-, and interferon-.gamma.mediated diseases using the compositions of this invention. Interleukin-1 (IL-1) is a major pro-inflammatory and immunoregulatory protein that stimulates fibroblast differentiation and proliferation, the production of prostaglandins, collagenase and phospholipase by synovial cells and chondrocytes, basophil and eosinophil degranulation and neutrophil activation. Oppenheim, J. H. et al, Immunology Today, 7, pp. 45-56 (1986). As such, it is involved in the pathogenesis of chronic and acute inflammatory and autoimmune diseases. For example, in rheumatoid arthritis, IL-1 is both a mediator of inflammatory symptoms and of the destruction of the cartilage proteoglycan in afflicted joints. Wood, D. D. et al., Arthritis Rheum. 26, 975, (1983); Pettipher, E. J. et al., Proc. Natl. Acad. Sci. USA 71, 295 (1986); Arend, W. P. and Dayer, J. M., Arthritis Rheum. 38, 151 (1995). IL-1 is also a highly potent bone resorption agent. Jandiski, J. J., J. Oral Path 17, 145 (1988); Dewhirst, F. E. et al., J. Immunol. 8, 2562 1985). It is alternately referred to as "osteoclast activating factor" in destructive bone diseases such as osteoarthritis and multiple myeloma. Bataille, R. et al., Int. J. Clin. Lab. Res. 21(4), 283 (1992). In certain proliferative disorders, such as acute myelogenous leukemia and multiple myeloma, IL-1 can promote tumor cell growth and adhesion. Bani, M. R., J.

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Natl. Cancer Inst. 83, 123 (1991); Vidal-Vanaclocha, F., Cancer Res. 54, 2667 (1994). In these disorders, IL-1 also stimulates production of other cytokines such as IL-6, which can modulate tumor development (Tartour et al., Cancer Res. 54, p. 6243 (1994). IL-1 is predominantly produced by peripheral blood monocytes as part of the inflammatory response and exists in two distinct agonist forms, IL-1.alpha. and IL-1.beta. Mosely, B. S. et al., Proc. Nat. Acad. Sci., 84, pp. 4572-4576 (1987); Lonnemann, G. et al., Eur. J. Immunol., 19, pp. 1531-1536 (1989). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Protection of neurological tissue by direct CNS perfusion cooling Inventor(s): Barnitz, James C.; (Schwenksville, PA), Frazer, Glenn D.; (Wynnewood, PA), Hesson, David P.; (Malvern, PA), Pelura, Timothy J.; (Malvern, PA) Correspondence: Allen Bloom; C/o Dechert; Princeton Pike Corporation Center; P.O. Box 5218; Princeton; NJ; 08543-5218; US Patent Application Number: 20030163181 Date filed: December 9, 2002 Abstract: Provided, among other things, is a method of treating, in an animal, an injury that is stroke, traumatic brain injury including traumatic surgical brain injury, brain hemorrhage other than stroke, spinal cord traumatic injury including spinal cord surgical trauma, infection, ischemia caused by surgical intervention, CNS injury caused by cardiac arrest, encephalitis or encephalomyelitis not due to infection, comprising: (a) creating a flow pathway, with an instillation catheter and an effluent catheter, that provides liquid flow in the vicinity of the injury; (b) instilling into the flow pathway an cerebrospinal perfusion fluid having a temperature from (i) 4.degree. C. as a lower temperature to (ii) 4.degree. C. below normal temperature of the animal; and (c) maintaining perfusion through the flow pathway for at least 12 hours of the cerebrospinal perfusion fluid having a temperature, at the point of instillation, from (i) 4.degree. C. as a lower temperature to (ii) 4.degree. C. below normal temperature of the animal. Excerpt(s): This application claims priority of U.S. Ser. No. 60/339,978, filed Dec. 7, 2001 and U.S. Ser. No. 60/339,859, filed Dec. 12, 2001. This invention relates to a method of producing directed cooling of neural tissue (hypothermia) which is useful for treating neurologic diseases and conditions that cause death or damage to neurological tissue, such as stroke, traumatic brain injury (TBI), brain hemorrhage, spinal cord traumatic injury, infection, ischemia caused by surgical intervention or ischemic injury caused by cardiac arrest. It has been understood for 50 years that lowering body temperature to 2835.degree. C. provides protection of organs and tissues (Bigelos et al., 1950). Hypothermia is most often induced via external cooling of the entire body by application of ice, cold fluids, cooling blankets or all of these techniques to the skin of the patient. These methods provide total body (global) hypothermia to the patient effecting all organ systems. This approach has significant drawbacks in the treatment of neurologic diseases or conditions. First, the time required to cool the entire body is long and the length of time the entire body can be cooled is limited (Ringelstein et al., Neurology 42:289-98, 1992). This is very important in an emergency situation. Second, global cooling causes cardiovascular problems, such as cardiac arrhythmias, reduced cardiac output, increased systemic vascular resistance, pulmonary edema, increased blood viscosity, coagulopathy and leukopenia. These effects may result in damage to the heart and other organs, (McCallum, Canadian J. Surgery 6:457-60, 1990).

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Treatment of shoulder dysfunction using a percutaneous intramuscular stimulation system Inventor(s): Fang, Zi-Ping; (Mayfield Village, OH), Walker, Maria E.; (Shaker Heights, OH) Correspondence: Ryan Kromholz & Manion, S.C.; Post Office Box 26618; Milwaukee; WI; 53226; US Patent Application Number: 20030014088 Date filed: May 3, 2002 Abstract: A method of treating shoulder dysfunction involves the use of a percutaneous, intramuscular stimulation system. A plurality of intramuscular stimulation electrodes are implanted directly into select shoulder muscles of a patient who has suffered a disruption of the central nervous system such as a stroke, traumatic brain injury, spinal cord injury or cerebral palsy. An external microprocessor based multi-channel stimulation pulse train generator is used for generating select electrical stimulation pulse train signals. A plurality of insulated electrode leads percutaneously, electrically interconnect the plurality of intramuscular stimulation electrodes to the external stimulation pulse train generator, respectively. Stimulation pulse train parameters for each of the stimulation pulse train output channels are selected independently of the other channels.The shoulder is evaluated for subluxation in more than one dimension. More than one muscle or muscle group is simultaneously subjected to a pulse train dosage. Preferably, the at least two dosages are delivered asynchronously to two muscle groups comprising the supraspinatus in combination with the middle deltoid, and the trapezious in combination with the posterior deltoid. Excerpt(s): The present invention relates to the art of therapeutic neuromuscular stimulation. It finds particular application for use by human patients who are paralyzed or partially paralyzed due to cerebrovascular accidents such as stroke or the like. The invention is useful for retarding, preventing muscle disuse atrophy and even improving muscular condition, maintaining or improving extremity range-of-motion, facilitating voluntary motor function, relaxing spastic muscles, and increasing blood flow to select muscles of the shoulder. Additional benefits of the invention may include improved alignment and decreased pain. The invention is particularly useful for the treatment of shoulder dysfunction. An estimated 555,000 persons are disabled each year in the United States of America by cerebrovascular accidents (CVA) such as stroke. Many of these patients are left with partial or complete paralysis of an extremity including for example, hemiplegic subluxation (incomplete dislocation) of the shoulder joint. This is a common occurrence and has been associated with chronic and debilitating pain among stroke survivors. In stroke survivors experiencing shoulder pain, motor recovery is frequently poor and rehabilitation is impaired. Thus, the patient may not achieve his/her maximum functional potential and independence. Therefore, prevention and treatment of subluxation in stroke patients is a priority. There is a general acknowledgment by healthcare professionals of the need for improvement in the prevention and treatment of shoulder subluxation. Conventional intervention includes the use of orthotic devices; such as slings and supports, to immobilize the joint in an attempt to maintain normal anatomic alignment. The effectiveness of these orthotic devices varies with the individual. Also, many authorities consider the use of slings and arm supports to be controversial or even contraindicated because of the potential

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complications from immobilization including disuse atrophy and further disabling contractures. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Use of amino-isoxazolidone compounds for treatment of memory impairment following traumatic brain injury Inventor(s): Fakouhi, Daniel T.; (Wilmette, IL), Herting, Robert L.; (Park Ridge, IL), Williams, J. Michael; (Philadelphia, PA) Correspondence: J. Timothy Keane; Pharmacia Corporation; Corporate Patent Department; 800 North Lindbergh BLVD. - O4e; ST. Louis; MO; 63167; US Patent Application Number: 20030073730 Date filed: October 16, 2002 Abstract: A class of amino-isoxazolidone compounds is described for use in treatment of memory impairment associated with Traumatic Brain Injury ("TBI"). Preferred compounds of this class are D-cycloserine and its prodrugs. Excerpt(s): This invention is in the field of clinical neurology and relates specifically to compounds, formulations and methods for treatment of memory impairment or deficit following or associated with Traumatic Brain Injury ("TBI"). In a summary of epidemiology of Traumatic Brain Injury ("TBI") in the United States, an overall incidence of 200 per 100,000 people was reported [J. F. Kraus, In: Neuroepidemiology, 335-357, D. W. Anderson & D. H. Schoenberg, eds., CRC Press, Boca Raton, Fla., (1991)]. TBI patients may develop a number of neuropsychological disorders, including severe memory impairment. Epidemiological studies of cognitive impairment following Traumatic Brain Injury have not been reported. However, outcome studies using consecutive admissions to trauma centers suggest that the incidence rate leading to cognitive impairment is approximately 40-80% of all cases of Traumatic Brain Injury in which the patient was in a coma for at least one-half hour [J. M Williams et al, J. Neurosurg., 61, 581-585 (1984); M. R. Bond et al, Scand. J. of Rehab. Med., 8, 127-133 (1976); G. S. Carlsson et al, J. of Neurosurgery, 67, 507-513 (1986); S. Dikmen et al, Arch. Physical Medicine and Rehabilitation, 67, 507-513 (1986); S. Dikmen et al, J. Neurology, Neurosurgery and Psychiatry, 50, 1613-1618 (1987); H. S. Levin et al, J. Neurosurgery, 50, 412-422, (1979)] Post-traumatic memory impairment persists through the patient's physical recovery and may become the permanent sequelae of the injury [G. S. Carlsson et al, J. of Neurosurgery, 67, 507-513 (1986); S. Dikmen et al, Arch. Physical Medicine and Rehabilitation, 67, 507-513 (1986); S. Dikmen et al, J. Neurology, Neurosurgery and Psychiatry, 50, 1613-1618 (1987); H. S. Levin et al, J. Neurosurgery, 50, 412-422, (1979)). Traumatic injury of the brain produces mechanical injury of neurons, axonal stretching and neuronal degeneration. Compression injury of neural tissues may also result from increased intracranial pressure due to hematoma and diffuse swelling. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Use of benzopyranols to treat neurological disorders Inventor(s): Evans, John Morris; (Roydon, GB), Parsons, Andrew; (Arlesey, GB), Thompson, Mervyn; (Harlow, GB), Upton, Neil; (Harlow, GB) Correspondence: Glaxosmithkline; Corporate Intellectual Property - Uw2220; P.O. Box 1539; King OF Prussia; PA; 19406-0939; US Patent Application Number: 20020010209 Date filed: July 19, 2001 Abstract: Benzopyran derivatives and analogs are disclosed as useful for the treatment and/or prophylaxis of degenerative diseases such as Huntingdon's chorea, schizophrenia, neurological deficits associated with AIDS, sleep disorders (including circadian rhythm disorders, insomnia and narcolepsy), tics (e.g. Giles de la Tourette's syndrome), traumatic brain injury, tinnitus, neuralgia, especially trigeminal neuralgia, neuropathic pain, dental pain, cancer pain, inappropriate neuronal activity resulting in neurodysthesias in diseases such as diabetes, MS and motor neurone disease, ataxias, muscular rigidity (spasticity), temporomandibular joint dysfunction. Excerpt(s): This invention relates to a novel method of treatment. EP-A-0 126 311 discloses substituted benzopyran compounds having blood pressure lowering activity, including 6-acetyl-trans-4-(4-fluoroben- zoylamino)-3,4-dihydro-2,2-dimethyl-2H-1benzopyran-3-ol. Also EP-A-0 376 524, EP-A-0 205 292, EP-A-0 250 077, EP-A-0 093 535, EP-A-0 150 202, EP-A-0 076 075 and WO/89/05808 (Beecham Group plc) describe certain benzopyran derivatives which possess anti-hypertensive activity. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Use of GABAA inverse agonists in combination with nicotine receptor partial agonists, estrogen, selective estrogen modulators, or vitamin E for the treatment of cognitive disorders Inventor(s): Villalobos, Anabella; (Niantic, CT) Correspondence: Pfizer Inc; 150 East 42nd Street; 5th Floor - Stop 49; New York; NY; 10017-5612; US Patent Application Number: 20020193360 Date filed: February 26, 2002 Abstract: A pharmaceutical composition and method of treatment of diseases of cognitive dysfunction in a mammal comprising administration of a GABA.sub.A inverse agonist or a pharmaceutically acceptable salt thereof; and a nicotine receptor partial agonist, an estrogenic agent, selective estrogen receptor modulator or vitamin E or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier. The GABA.sub.A inverse agonist, and nicotine receptor partial agonist, estrogen, selective estrogen receptor modulator or vitamin E are present in amounts that render the composition effective enhancing cognition or in the treatment of diseases of cognitive dysfunction including but not limited to Alzheimer's Disease (AD), mild cognitive impairment, age-related cognitive decline, vascular dementia, Parkinson's disease, Huntington's disease, memory impairment associated with depresssion or anxiety, schizophrenia, Down's syndrome, stroke, traumatic brain injury (TBI), AIDS associated dementia and attention deficit disorder. The method of using these compositions is also disclosed.

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Excerpt(s): This application claims priority from U.S. provisional application Serial No. 60/272,566, filed Mar. 1, 2001, which is incorporated herein by reference in its entirety. The present invention relates to pharmaceutical compositions for the prevention and/or treatment of diseases of cognitive dysfunction in a mammal comprising GABA.sub.A inverse agonists in combination with nicotine receptor partial agonists (NRPA), estrogen, selective estrogen receptor modulators (SERMS) or vitamin E and a pharmaceutically acceptable carrier. The pharmaceutical compositions are useful in enhancing memory in patients suffering from diseases of cognitive dysfunction such as, but not limited to, Alzheimer's Disease (AD), mild cognitive impairment, age-related cognitive decline, vascular dementia, Parkinson's disease, Huntington's disease, memory impairment associated with depression or anxiety, schizophrenia, Down's syndrome, stroke, traumatic brain injury (TBI), AIDS associated dementia and attention deficit disorder. Cognitive and/or degenerative brain disorders are characterized clinically by progressive loss of memory, cognition, reasoning, judgment and emotional stability that gradually leads to profound mental deterioration and ultimately death. In an example of such disorders, AD is a common cause of progressive mental failure (dementia) in aged humans and is believed to represent the fourth most common medical cause of death in the United States. In particular, AD is associated with degeneration of cholinergic neurons in the basal forebrain that play a fundamental role in cognitive functions, including memory [Becker et al., Drug Development Research, 12, 163-195 (1988)]. Cognitive and/or degenerative brain disorders have been observed in varied races and ethnic groups worldwide and presents a major public health problem. These diseases are currently estimated to affect about two to three million individuals in the United States alone. These diseases are incurable with presently used medications and will increase worldwide as the human lifespan increases. 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 traumatic brain injury, 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 “traumatic brain injury” (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 traumatic brain injury. You can also use this procedure to view pending patent applications concerning traumatic brain injury. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

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CHAPTER 6. BOOKS ON TRAUMATIC BRAIN INJURY Overview This chapter provides bibliographic book references relating to traumatic brain injury. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on traumatic brain injury 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 “traumatic brain injury” (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 traumatic brain injury: •

Mild Traumatic Brain Injury: A Therapy and Resource Manual Source: San Diego, CA: Singular Publishing Group, Inc. 1998. 260 p. 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: $49.95 plus shipping and handling. ISBN: 1565938275. Summary: This book is a therapy and reference manual created in response to the unique needs of adolescents and adults who have sustained mild to moderate traumatic brain injuries (MTBI). The authors focus on providing practical suggestions for developing individualized therapy tasks to promote a client's successful return to the demands of the home, school, or work environment. Nine chapters cover the diversified roles of the speech language pathologist, the assessment of MTBI, treatment options

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(including establishing a positive therapeutic relationship), treating complex attention impairments, treating functional and prospective memory impairments, treating word retrieval and thought formulation impairments, treating information processing impairments (auditory and visual), treating executive functioning impairments, and therapy documentation, transition, and discharge. Each chapter includes therapy tasks, home practice tasks, and suggestions for families (including patient and family handouts). The text concludes with a reference list and subject index. 26 references. •

Pediatric Traumatic Brain Injury: Proactive Intervention Source: San Diego, CA: Singular Publishing Group, Inc. 1994. 281 p. 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: $42.50 plus shipping and handling. ISBN: 1565931688. Summary: This book is designed for professionals from a variety of disciplines who are challenged daily by children and adolescents with traumatic brain injury (TBI). The authors explain their philosophy for planning and implementing programming for this group of youngsters. The book is divided into four major parts: Part I provides an overview of TBI in the pediatric population; Part II describes how to use problemsolving techniques to conduct functional assessments; Part III suggests treatment approaches based on a proactive, problem-solving approach; and, using a case study, Part IV illustrates this approach to intervention. Each chapter begins with an introduction and list of objectives for the reader and ends with several summary guidelines and a reference list. A brief subject index concludes the volume.

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Coping with Mild Traumatic Brain Injury Source: Garden City Park, NY: Avery Publishing Group, Inc. 1998. 352 p. Contact: Available from Avery Publishing Group, Inc. 120 Old Broadway, Garden City Park, NY 11040. (800) 548-5757. PRICE: $14.95 (retail price); bulk rates available. ISBN: 0895297914. Summary: This book presents a guide to coping with mild traumatic brain injury (MTBI), a problem resulting from car accidents, falls, sports injuries, work-related accidents, and physical assault. The authors note that MTBI is commonly misdiagnosed because the symptoms are unpredictable and can be mistaken for those of many other conditions. The authors first review how the brain works and how it can be injured, the procedures used to diagnose brain injury, and the different treatments available. They then examine the most common physical, mental, and psychological symptoms of brain injury, explaining why each occurs and what can be done about it, and offering practical suggestions for coping with the problem. Also covered are financial, insurance, and family issues; the rehabilitation process; and eventual outcomes. Most of the chapters deal with one particular aftereffect of MTBI and provide a real-life story, an explanation of why the symptom or problem occurs, information about treatment, and practical suggestions for coping with the problem. Chapters cover specific problems including fatigue, headaches, dizziness, problems with sexuality, vision problems, hearing problems, sensory and metabolic disturbances, muscular and motor problems, and seizures. Other problems relate to attention and concentration, memory, reasoning and understanding, speech and language, academic performance, moods and behaviors, psychiatric disorders, and grieving. The book concludes with an extensive resource section that provides additional guidance and sources of support.

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193

Traumatic Brain Injury in Children and Adolescents: A Sourcebook for Teachers and Other School Personnel, Second Edition Source: Austin, TX: PRO-ED, Inc. 1999. 149 pp. ISBN: 0-89079-805-2. Contact: Available from PRO-ED, Inc. 8700 Shoal Creek Boulevard, Austin, TX 787576897. (800) 897-3202; Fax (800) 397-7633. Web site: http://www.proedinc.com. PRICE: $30.00 plus shipping and handling. Summary: This guide provides new and updated information for all educators who are serving students with traumatic brain injury (TBI.) The text is easy to read and offers an overview of the entire spectrum of issues related to TBI. In addition to describing the short-and long-term causes and consequences of TBI, this sourcebook presents techniques and procedures to successfully return the child to school following an injury. Additionally, this sourcebook provides practical suggestions that will help teachers develop appropriate educational programs for students in the years following TBI. Annotated bibliography, glossary, references, and index included.

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Children with Traumatic Brain Injury: A Parent's Guide Source: Bethesda, MD. Woodbine House Special Needs Collection. Contact: Available from Woodbine House. 6510 Bells Mill Rd., Bethesda, MD 20817. 301897-3570; 800-843-7323. Web site: www.woodbinehouse.com. PRICE: $17.95 plus shipping and handling. ISBN: 0-933149-99-9 (paperback). 482pp. Summary: This reference book provides parents of children with traumatic brain injury (TBI) with support, information, and coping skills to help with their child's recovery process. Written by a team of professionals and experts, the guide covers diagnosis, medical and rehabilitation issues, cognitive and behavioral effects, emotional adjustment, education, and prevention. Includes 40 photographs, a glossary, and reading and resource lists.

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

A Practical Guide to Head Injury Management by Paul V. Marks (Editor), Christopher B. Lavy (Editor); ISBN: 0702016152; http://www.amazon.com/exec/obidos/ASIN/0702016152/icongroupinterna

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Acute Head Injury: Practical Management in Rehabilitation (Therapy in Practice Series, 13) by Ruth Garner; ISBN: 0412324202; http://www.amazon.com/exec/obidos/ASIN/0412324202/icongroupinterna

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Adult Head Injury Rehabilitation: Community Re-entry by Mark Ylvisaker (Editor), Eva Marie Gobble (Editor); ISBN: 0850666619; http://www.amazon.com/exec/obidos/ASIN/0850666619/icongroupinterna

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Advances in Understanding Communication Disorders After Traumatic Brain Injury: A Special Issue of the Journal Aphasiology by Skye McDonald (Editor); ISBN: 1841699004; http://www.amazon.com/exec/obidos/ASIN/1841699004/icongroupinterna

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Analysis, Understanding, and Presentation of Cases Involving Traumatic Brain Injury by Charles N. Simkins; ISBN: 0927093014; http://www.amazon.com/exec/obidos/ASIN/0927093014/icongroupinterna

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Anesthetic Management of Acute Head Injury by Arthur M., M.D. Lam (Editor); ISBN: 0070361274; http://www.amazon.com/exec/obidos/ASIN/0070361274/icongroupinterna

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Assisting Survivors of Traumatic Brain Injury: The Role of Speech-Language Pathologists by Karen Hux (Editor), Victoria Sutton; ISBN: 0890798958; http://www.amazon.com/exec/obidos/ASIN/0890798958/icongroupinterna

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Assistive Technology in Traumatic Brain Injury Vocational Rehabilitation by C. Gerald Warren, et al; ISBN: 1878205072; http://www.amazon.com/exec/obidos/ASIN/1878205072/icongroupinterna

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Behind the Shadows in Silent Screams: Success Stories of Traumatic Brain Injury Cases by Maria A. Hernandez; ISBN: 1401061133; http://www.amazon.com/exec/obidos/ASIN/1401061133/icongroupinterna

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Brain Injury Rehabilitation: Adaptive Driving After Traumatic Brain Injury (Professional Series, Vol 5) by C. Alan Hopewell; ISBN: 1882855523; http://www.amazon.com/exec/obidos/ASIN/1882855523/icongroupinterna

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Brain Injury Rehabilitation: Applied Behavior Analysis in Brain Injury Rehab (Professional Series on Traumatic Brain Injury Volume 11) by William Burke (Editor); ISBN: 1882855426; http://www.amazon.com/exec/obidos/ASIN/1882855426/icongroupinterna

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Brain Injury Rehabilitation: Developing Self Control (Hdi Professional Series on Traumatic Brain Injury, No 14) by Michael D. Wesolowski, et al; ISBN: 1882855590; http://www.amazon.com/exec/obidos/ASIN/1882855590/icongroupinterna

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Brain Injury Rehabilitation: Managing Anger & Aggression (Professional Series on Traumatic Brain Injury Volume 6) by Burke William H. (Editor); ISBN: 1882855531; http://www.amazon.com/exec/obidos/ASIN/1882855531/icongroupinterna

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Brain Injury Rehabilitation: Managing Anger and Aggression (Hdi Professional Series on Traumatic Brain Injury, Vol 6) by Michael D. Wesolowski (Editor), William H. Burke (Editor); ISBN: 1882855132; http://www.amazon.com/exec/obidos/ASIN/1882855132/icongroupinterna

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Brain Injury Rehabilitation: Managing Attention Deficits (Hdi Professional Series on Traumatic Brain Injury, No 7) by Richard Guare, William H. Burke (Editor); ISBN: 1882855493; http://www.amazon.com/exec/obidos/ASIN/1882855493/icongroupinterna

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Brain Storms: Recovery from Traumatic Brain Injury by John Cassidy; ISBN: 0929162390; http://www.amazon.com/exec/obidos/ASIN/0929162390/icongroupinterna

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195

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Careers of Care: Survivors of Traumatic Brain Injury and the Response of Health and Social Care by P. E. Higham, Kay Phelps; ISBN: 1857424255; http://www.amazon.com/exec/obidos/ASIN/1857424255/icongroupinterna

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Childhood Traumatic Brain Injury: Diagnosis, Assessment, and Intervention by Erin D. Bigler (Editor), et al; ISBN: 0890797188; http://www.amazon.com/exec/obidos/ASIN/0890797188/icongroupinterna

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Children With Traumatic Brain Injury: A Parent's Guide (The Special Needs Collection) by Lisa Schoenbrodt (Editor); ISBN: 0933149999; http://www.amazon.com/exec/obidos/ASIN/0933149999/icongroupinterna

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Children's Head Injuries by David Johnson, Maria A. Wyke; ISBN: 0863771882; http://www.amazon.com/exec/obidos/ASIN/0863771882/icongroupinterna

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Children's Head Injury: Who Cares by David A. Johnson, et al; ISBN: 0850668468; http://www.amazon.com/exec/obidos/ASIN/0850668468/icongroupinterna

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Children's health : protecting our most precious resource : hearing before the Subcommittee on Public Health of the Committee on Health, Education, Labor, and Pensions, United States Senate, One Hundred Sixth Congress, first session, on examining issues relating to children's health, focusing on autism, asthma, and traumatic brain injury, September 16, 1999 (SuDoc Y 4.L 11/4:S.HRG.106-214); ISBN: 0160597218; http://www.amazon.com/exec/obidos/ASIN/0160597218/icongroupinterna

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Clinical Management of Communication Problems in Adults With Traumatic Brain Injury (The Rehabilitation Institute of Chicago Publication Series) by Anita Halper, et al; ISBN: 0834202794; http://www.amazon.com/exec/obidos/ASIN/0834202794/icongroupinterna

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Cognitive Communication Disorders Following Traumatic Brain Injury : A Practical Guide by Freund, et al; ISBN: 0761630376; http://www.amazon.com/exec/obidos/ASIN/0761630376/icongroupinterna

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Cognitive Rehabilitation for Persons With Traumatic Brain Injury by Jeffrey S. Kreutzer (Editor), Paul Wehman (Editor); ISBN: 1883315158; http://www.amazon.com/exec/obidos/ASIN/1883315158/icongroupinterna

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Cognitive Rehabilitation for Persons With Traumatic Brain Injury: A Functional Approach by Jeffrey S. Kreutzer, Paul H. Wehman (Editor); ISBN: 1557660719; http://www.amazon.com/exec/obidos/ASIN/1557660719/icongroupinterna

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Cognitive-communication disorders following traumatic brain injury : a practical guide; ISBN: 0884501639; http://www.amazon.com/exec/obidos/ASIN/0884501639/icongroupinterna

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Communication Disorders Following Traumatic Brain Injury; ISBN: 0316092517; http://www.amazon.com/exec/obidos/ASIN/0316092517/icongroupinterna

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Communication Disorders Following Traumatic Brain Injury (Brain Damage, Behaviour and Cognition) by Skye McDonald (Editor), et al; ISBN: 0863777252; http://www.amazon.com/exec/obidos/ASIN/0863777252/icongroupinterna

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Communication Disorders Following Traumatic Brain Injury: Management of Cognitive, Language, and Motor Impairments by David R. Beukelman, Kathryn M. Yorkston (Editor); ISBN: 089079295X; http://www.amazon.com/exec/obidos/ASIN/089079295X/icongroupinterna

196


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Community Integration Following Traumatic Brain Injury by Jeffrey S. Kreutzer (Editor), Paul H. Wehman (Editor); ISBN: 155766045X; http://www.amazon.com/exec/obidos/ASIN/155766045X/icongroupinterna

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Community integration of individuals with traumatic brain injury (SuDoc ED 1.48:16/8) by U.S. Dept of Education; ISBN: B00010MSAE; http://www.amazon.com/exec/obidos/ASIN/B00010MSAE/icongroupinterna

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Confronting Traumatic Brain Injury : Devastation, Hope, and Healing by William J. Winslade, James S. Brady; ISBN: 0300079427; http://www.amazon.com/exec/obidos/ASIN/0300079427/icongroupinterna

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Continuing Therapeutic Education for the School-Age Child with Traumatic Brain Injury by Dorothy, PhD., CCC-SLP McKerns, Leslie McKerns, BA, BS Motchkavitz; ISBN: 076164346X; http://www.amazon.com/exec/obidos/ASIN/076164346X/icongroupinterna

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Coping With Mild Traumatic Brain Injury (Coping With.) by Diane Roberts Stoler, et al; ISBN: 0895297914; http://www.amazon.com/exec/obidos/ASIN/0895297914/icongroupinterna

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Cracked: Recovering after Traumatic Brain Injury by Lynsey Calderwood; ISBN: 1843100657; http://www.amazon.com/exec/obidos/ASIN/1843100657/icongroupinterna

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Educating students with traumatic brain injuries : a resource and planning guide (SuDoc ED.6/2:B 72/1996) by Sandra L. Corbett; ISBN: 1573370312; http://www.amazon.com/exec/obidos/ASIN/1573370312/icongroupinterna

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Educator guidelines for serving students with traumatic brain injuries (SuDoc ED 1.310/2:373520) by U.S. Dept of Education; ISBN: B00010NH5Y; http://www.amazon.com/exec/obidos/ASIN/B00010NH5Y/icongroupinterna

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Educators Manual: What Educators Need to Know About Students With Traumatic Brain Injury by Natl Head Injury Foundation, et al; ISBN: 0927093006; http://www.amazon.com/exec/obidos/ASIN/0927093006/icongroupinterna

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Enhancing social support and integration for students with traumatic brain injury final report (SuDoc ED 1.310/2:416607) by U.S. Dept of Education; ISBN: B00010YRZ8; http://www.amazon.com/exec/obidos/ASIN/B00010YRZ8/icongroupinterna

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Epilepsy after non-missile head injuries by Bryan Jennett; ISBN: 0815148666; http://www.amazon.com/exec/obidos/ASIN/0815148666/icongroupinterna

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Essential Radiology in Head Injury: A Diagnostic Atlas of Skull Trauma by Louis Kreel, D. W. H. Mok; ISBN: 0433000414; http://www.amazon.com/exec/obidos/ASIN/0433000414/icongroupinterna

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Family Support Programs and Rehabilitation: A Cognitive-Behavioral Approach to Traumatic Brain Injury (Critical Issues in Neuropsychology) by Hamish P.D. Godfrey, Louise Margaret Smith; ISBN: 0306449323; http://www.amazon.com/exec/obidos/ASIN/0306449323/icongroupinterna

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Fraud and abuse in the head injury rehabilitation industry : twenty-fifth report (SuDoc Y 1.1/8:102-1059) by U.S. Congressional Budget Office; ISBN: B00010CEYE; http://www.amazon.com/exec/obidos/ASIN/B00010CEYE/icongroupinterna

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Group treatment for head injury : a linguistic and cognitive approach by Marjorie Feinstein-Whittaker; ISBN: 0884504514; http://www.amazon.com/exec/obidos/ASIN/0884504514/icongroupinterna

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197

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Head injuries : tumors of the crebellar region; ISBN: 3540089640; http://www.amazon.com/exec/obidos/ASIN/3540089640/icongroupinterna

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Head Injuries: Medical Subject Analysis and Research Guide With Bibliography by Angelina Ada Crowson; ISBN: 0881642584; http://www.amazon.com/exec/obidos/ASIN/0881642584/icongroupinterna

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Head injuries: proceedings of an international symposium held in Edinburgh and Madrid, 2nd to 10th April 1970; ISBN: 0443008329; http://www.amazon.com/exec/obidos/ASIN/0443008329/icongroupinterna

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Head Injuries: Prognosis, Evoked Potentials, Microsurgery, Brain Death by R.A. Frowein (Editor), Deutsche Gesellschaft F Ur Neurochirurgi; ISBN: 0387505504; http://www.amazon.com/exec/obidos/ASIN/0387505504/icongroupinterna

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Head Injury; ISBN: 0556420013; http://www.amazon.com/exec/obidos/ASIN/0556420013/icongroupinterna

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Head Injury and Postconcussive Syndrome by Matthew, MD Rizzo (Editor), Daniel, Phd Tranel (Editor); ISBN: 0443089647; http://www.amazon.com/exec/obidos/ASIN/0443089647/icongroupinterna

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Head Injury and the Family a Life and Living Perspective: A Life and Living Perspective by Arthur E. Dell Orto, et al; ISBN: 1878205617; http://www.amazon.com/exec/obidos/ASIN/1878205617/icongroupinterna

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Head Injury Education: A Group Therapy Manual by Martin van der Broek, Beverley Dayus; ISBN: 0863882293; http://www.amazon.com/exec/obidos/ASIN/0863882293/icongroupinterna

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Head Injury Rehabilitation: An Overview (Hdi Professional Series on Traumatic Brain Injury, No 1) by William H. Burke, et al; ISBN: 1882855086; http://www.amazon.com/exec/obidos/ASIN/1882855086/icongroupinterna

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Head Injury Rehabilitation: Developing Adaptive Work Behaviors (Professional Series , Vol 17) by Frank D. Lewis; ISBN: 1882855248; http://www.amazon.com/exec/obidos/ASIN/1882855248/icongroupinterna

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Head Injury: Pathophysiology and Management of Severe Closed Injury by Peter Reilly; ISBN: 0412585405; http://www.amazon.com/exec/obidos/ASIN/0412585405/icongroupinterna

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Head Injury: The Complexities of Treatment by J. Rodney Watts; ISBN: 0074701525; http://www.amazon.com/exec/obidos/ASIN/0074701525/icongroupinterna

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Helmets for all : nice looking helmets reduce head injuries by Ingemar Ahlström; ISBN: 917398342X; http://www.amazon.com/exec/obidos/ASIN/917398342X/icongroupinterna

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In home family supports what families of youngsters with traumatic brain injury really need (SuDoc ED 1.310/2:341174) by Betty Pieper; ISBN: B00010EIVG; http://www.amazon.com/exec/obidos/ASIN/B00010EIVG/icongroupinterna

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In Search of Wings: A Journey Back from Traumatic Brain Injury by Beverley Bryant; ISBN: 1882332008; http://www.amazon.com/exec/obidos/ASIN/1882332008/icongroupinterna

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Injuries and response what parents and professional providers are telling us about treating children with traumatic brain injury (SuDoc ED 1.310/2:341176) by Betty

198


Pieper; ISBN: B00010ETCE; http://www.amazon.com/exec/obidos/ASIN/B00010ETCE/icongroupinterna •

Introduction to Head Injuries by Asoke K. Bagchi; ISBN: 0195611519; http://www.amazon.com/exec/obidos/ASIN/0195611519/icongroupinterna

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Living With Head Injury; ISBN: 9992292873; http://www.amazon.com/exec/obidos/ASIN/9992292873/icongroupinterna

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Management and Prognosis of Severe Traumatic Brain Injury (Book ) with CDROM by Brain Trauma Foundation, American Association of Neurological Sur; ISBN: 097031440X; http://www.amazon.com/exec/obidos/ASIN/097031440X/icongroupinterna

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Management of Communication & Language Deficits (Professional Series on Traumatic Brain Injury Series, Vol 20) by William H. Burke (Editor); ISBN: 1882855272; http://www.amazon.com/exec/obidos/ASIN/1882855272/icongroupinterna

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MANAGEMENT OF HEAD INJURIES Jennet; ISBN: 0803650183; http://www.amazon.com/exec/obidos/ASIN/0803650183/icongroupinterna

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Management of Minor Head Injuries by Ian Swann MB BS FRCS, et al; ISBN: 0412290804; http://www.amazon.com/exec/obidos/ASIN/0412290804/icongroupinterna

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Manual-Traumatic Brain Injury by *; ISBN: 0761687602; http://www.amazon.com/exec/obidos/ASIN/0761687602/icongroupinterna

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Medical Rehabilitation of Traumatic Brain Injury by Lawrence J. Horn (Editor), Nathan D. Zasler (Editor); ISBN: 1560530707; http://www.amazon.com/exec/obidos/ASIN/1560530707/icongroupinterna

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Mild to Moderate Head Injury by Julian Hoff, et al; ISBN: 0865420645; http://www.amazon.com/exec/obidos/ASIN/0865420645/icongroupinterna

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Mild Traumatic Brain Injury: A Clinician's Guide by Michael J. Raymond (Editor), et al; ISBN: 0890798095; http://www.amazon.com/exec/obidos/ASIN/0890798095/icongroupinterna

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Mild Traumatic Brain Injury: A Therapy and Resource Manual by Betsy S. Green, et al; ISBN: 1565938275; http://www.amazon.com/exec/obidos/ASIN/1565938275/icongroupinterna

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Minor Traumatic Brain Injury Handbook: Diagnosis and Treatment by Gary W. Jay; ISBN: 0849319552; http://www.amazon.com/exec/obidos/ASIN/0849319552/icongroupinterna

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Model family professional partnerships for interventions in children with traumatic brain injury (SuDoc ED 1.310/2:341175) by Betty Pieper; ISBN: B00010EIUW; http://www.amazon.com/exec/obidos/ASIN/B00010EIUW/icongroupinterna

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Neurobehavioural Disability and Social Handicap Following Traumatic Brain Injury (Brain Damage, Behaviour and Cognition) by Rodger Ll. Wood (Editor), et al; ISBN: 0863778895; http://www.amazon.com/exec/obidos/ASIN/0863778895/icongroupinterna

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Neuropsychiatry of Traumatic Brain Injury by Stuart C. Yudofsky (Editor), et al; ISBN: 0880485388; http://www.amazon.com/exec/obidos/ASIN/0880485388/icongroupinterna

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199

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Neuropsychological Management of Mild Traumatic Brain Injury by Sarah A. Raskin, Catherine A. Mateer (Editor); ISBN: 0195085272; http://www.amazon.com/exec/obidos/ASIN/0195085272/icongroupinterna

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Nothing short of a miracle : a chronicle of a head injury survivor by Michael A. Peake; ISBN: 0963825402; http://www.amazon.com/exec/obidos/ASIN/0963825402/icongroupinterna

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Occupational Therapy Approaches to Traumatic Brain Injury by Jerry A. Johnson (Editor), Laura Krefting (Editor); ISBN: 1560240644; http://www.amazon.com/exec/obidos/ASIN/1560240644/icongroupinterna

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Occupational Therapy Approaches to Traumatic Brain Injury; ISBN: 0560240643; http://www.amazon.com/exec/obidos/ASIN/0560240643/icongroupinterna

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Occupational therapy practice guidelines for adults with traumatic brain injury by Mary Vining Radomski; ISBN: 1569000433; http://www.amazon.com/exec/obidos/ASIN/1569000433/icongroupinterna

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Parenting a Child With Traumatic Brain Injury by Barry Kent Hughes; ISBN: 0398056463; http://www.amazon.com/exec/obidos/ASIN/0398056463/icongroupinterna

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Patterns of acute head injury by Reginald Hooper; ISBN: 0713141565; http://www.amazon.com/exec/obidos/ASIN/0713141565/icongroupinterna

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Pediatric Head Injuries Handbook by A. Loren Amacher; ISBN: 0875273378; http://www.amazon.com/exec/obidos/ASIN/0875273378/icongroupinterna

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Pediatric Traumatic Brain Injury by Stephen R. Hooper (Author), Jeffrey H. Snow (Author); ISBN: 0803951817; http://www.amazon.com/exec/obidos/ASIN/0803951817/icongroupinterna

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Pediatric Traumatic Brain Injury: Proactive Intervention (Neurogenic Communication Disorders) by Roberta, Ph.D. Depompei, Jean L. Blosser; ISBN: 1565931688; http://www.amazon.com/exec/obidos/ASIN/1565931688/icongroupinterna

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Penetrating Head Injuries by Dagi; ISBN: 0316170895; http://www.amazon.com/exec/obidos/ASIN/0316170895/icongroupinterna

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Physical Therapy for Traumatic Brain Injury (Clinics in Physical Therapy) by Jacqueline Montgomery (Editor); ISBN: 0443089086; http://www.amazon.com/exec/obidos/ASIN/0443089086/icongroupinterna

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Psychological Management of Traumatic Brain Injuries in Children and Adolescents (The Rehabilitation Institute of Chicago Publication Series) by Ellen Lehr; ISBN: 0834200953; http://www.amazon.com/exec/obidos/ASIN/0834200953/icongroupinterna

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PULSE Plus: Traumatic Brain Injury by Primedia; ISBN: 1401829465; http://www.amazon.com/exec/obidos/ASIN/1401829465/icongroupinterna

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Recovery After Traumatic Brain Injury (Institute for Research in Behavioral Neuroscience) by Barbara P. Uzzell (Editor), Henry H. Stonnington (Editor); ISBN: 0805818243; http://www.amazon.com/exec/obidos/ASIN/0805818243/icongroupinterna

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Rehabilitation for Traumatic Brain Injury by Maggie Campbell, Churchill Livingstone; ISBN: 0443061319; http://www.amazon.com/exec/obidos/ASIN/0443061319/icongroupinterna

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Rehabilitation of persons with traumatic brain injury (SuDoc HE 20.3046:16/1) by U.S. Dept of Health and Human Services; ISBN: B000111BK6; http://www.amazon.com/exec/obidos/ASIN/B000111BK6/icongroupinterna

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Rehabilitation of persons with traumatic brain injury : January 1988 through August 1998 plus selected earlier citations : 2563 citations (SuDoc HE 20.3615/2:98-1) by Ronald L. Gordner; ISBN: B00010Y32K; http://www.amazon.com/exec/obidos/ASIN/B00010Y32K/icongroupinterna

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Rehabilitation of Persons With Traumatic Brain Injury: Nih Consensus Statement by Kristjan T. Ragnarsson (Editor); ISBN: 0756725518; http://www.amazon.com/exec/obidos/ASIN/0756725518/icongroupinterna

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Rehabilitation of the Adult and Child With Traumatic Brain Injury by Mitchell Rosenthal (Editor), et al; ISBN: 0803603916; http://www.amazon.com/exec/obidos/ASIN/0803603916/icongroupinterna

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Report of the Consensus Development Conference on the Rehabilitation of Persons with Traumatic Brain Injury (SuDoc HE 20.3046:T 69/4) by U.S. Dept of Health and Human Services; ISBN: B000111JC6; http://www.amazon.com/exec/obidos/ASIN/B000111JC6/icongroupinterna

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Report of the Panel for Consensus Development Conference on Rehabilitation of Persons with Traumatic Brain Injury October 26-28, 1998 (SuDoc HE 20.3002:T 69/3/DRAFT) by U.S. Dept of Health and Human Services; ISBN: B00010YKIW; http://www.amazon.com/exec/obidos/ASIN/B00010YKIW/icongroupinterna

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Role of Reactive Oxygen Species in Traumatic Brain Injury: Experimental Studies in the Rat (Comprehensive Summaries of Uppsala Dissertations from the Faculty of mediciNe, 1048) by Niklas Marklund; ISBN: 9155450539; http://www.amazon.com/exec/obidos/ASIN/9155450539/icongroupinterna

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Rrhabilitation Traumatic Brain Injury by Baontke, et al; ISBN: 0750695811; http://www.amazon.com/exec/obidos/ASIN/0750695811/icongroupinterna

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Sexuality and the Person with Traumatic Brain Injury: A Guide for Families by Ernest R. Griffith, Sally Lemberg; ISBN: 0803644086; http://www.amazon.com/exec/obidos/ASIN/0803644086/icongroupinterna

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Shock, Sepsis, and Organ Failure: Brain Damage Secondary to HemorrhagicTraumatic Shock, Sepsis, and Traumatic Brain Injury by G. Schlag (Editor), et al; ISBN: 3540624198; http://www.amazon.com/exec/obidos/ASIN/3540624198/icongroupinterna

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Shock, Sepsis, and Organ Failure: I Brain Damage Secondary to HemorrhagicTraumatic Shock: II Brain Damage Secondary to Sepsis: III Brain Damage Secondary to Traumatic Brain Injury by Austria)/ Schlag, Gunther/ Traber, D. Wiggers Bernard Conference 1996 Krumbach; ISBN: 0387624198; http://www.amazon.com/exec/obidos/ASIN/0387624198/icongroupinterna

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Smile and Jump High! the True Story of Overcoming a Traumatic Brain Injury by Donald J. Lloyd, et al; ISBN: 0967388724; http://www.amazon.com/exec/obidos/ASIN/0967388724/icongroupinterna

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SOHBERG PERLWITZ IMPROVING PRAGMATIC SKILLS-HEAD INJURY; ISBN: 0761671625; http://www.amazon.com/exec/obidos/ASIN/0761671625/icongroupinterna

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Starting Again: Early Rehabilitation After Traumatic Brain Injury Or Other Severe Brain Lesion by Patricia M. Davies; ISBN: 0387559345; http://www.amazon.com/exec/obidos/ASIN/0387559345/icongroupinterna

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State of the Art Review: Traumatic Brain Injury, Vol. 3, No. 1 by Larry Norn, Nathan Cape; ISBN: 0932883656; http://www.amazon.com/exec/obidos/ASIN/0932883656/icongroupinterna

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The Evaluation and Treatment of Mild Traumatic Brain Injury by Nils R. Varney (Editor), Richard J. Roberts (Editor); ISBN: 080582393X; http://www.amazon.com/exec/obidos/ASIN/080582393X/icongroupinterna

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The Forensic Evaluation of Traumatic Brain Injury: A Handbook for Clinicians and Attorneys by Gregory J. Murrey (Editor), et al; ISBN: 0849320356; http://www.amazon.com/exec/obidos/ASIN/0849320356/icongroupinterna

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The Head injury survivor on campus issues and resources (SuDoc ED 1.310/2:312800) by U.S. Dept of Education; ISBN: B00010FEYQ; http://www.amazon.com/exec/obidos/ASIN/B00010FEYQ/icongroupinterna

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The incidence of traumatic brain injury in the United States (SuDoc ED 1.310/2:396467) by Joel Anton Forkosch; ISBN: B00010TF82; http://www.amazon.com/exec/obidos/ASIN/B00010TF82/icongroupinterna

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The incidence of traumatic brain injury in the United States (SuDoc ED 1.84/2:14) by Joel Anton Firkosch; ISBN: B00010R2YQ; http://www.amazon.com/exec/obidos/ASIN/B00010R2YQ/icongroupinterna

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The Mild Traumatic Brain Injury Workbook: Your Program for Regaining Cognitive Function and Overcoming Emotional Pain by Douglas J. Mason; ISBN: 1572243619; http://www.amazon.com/exec/obidos/ASIN/1572243619/icongroupinterna

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The Official Patient's Sourcebook on Traumatic Brain Injury: A Revised and Updated Directory for the Internet Age by Icon Health Publications; ISBN: 0597835373; http://www.amazon.com/exec/obidos/ASIN/0597835373/icongroupinterna

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The Rehabilitation of a Child With a Traumatic Brain Injury by Robert A. Hock (Editor); ISBN: 0398048967; http://www.amazon.com/exec/obidos/ASIN/0398048967/icongroupinterna

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The Rehabilitation of People With Traumatic Brain Injury by Buck H. Woo (Editor), Shanker Nesathurai (Editor); ISBN: 0632045175; http://www.amazon.com/exec/obidos/ASIN/0632045175/icongroupinterna

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The Role of the Family in Tbi Rehab (Professional Series on Traumatic Brain Injury; Vol 19) by William H. Burke (Editor); ISBN: 1882855469; http://www.amazon.com/exec/obidos/ASIN/1882855469/icongroupinterna

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The Traumatic Brain Injury Handbook by Camilia Anne Czubaj; ISBN: 0972123806; http://www.amazon.com/exec/obidos/ASIN/0972123806/icongroupinterna

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Therapeutic Education for the Child With Traumatic Brain Injury: From Coma to Kindergarten by Dorothy McKerns, Leslie McKerns Motchkavitz; ISBN: 0761642854; http://www.amazon.com/exec/obidos/ASIN/0761642854/icongroupinterna

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Through This Window: Views on Traumatic Brain Injury by Patricia I. Felton (Editor); ISBN: 096344610X; http://www.amazon.com/exec/obidos/ASIN/096344610X/icongroupinterna

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TIPTON-DIKENGIL FAMILY ARTICLES TRAUMATIC BRAIN INJURY; ISBN: 0761631283; http://www.amazon.com/exec/obidos/ASIN/0761631283/icongroupinterna

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Traumatic Brain Injury by Donald W. Marion (Editor); ISBN: 0865777276; http://www.amazon.com/exec/obidos/ASIN/0865777276/icongroupinterna

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Traumatic Brain Injury (Comprehensive Neurologic Rehabilitation, Vol 2) by Paul, M.D. Bach-Y-Rita; ISBN: 0939957183; http://www.amazon.com/exec/obidos/ASIN/0939957183/icongroupinterna

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Traumatic brain injury (SuDoc ED 1.310/2:431264) by U.S. Dept of Education; ISBN: B000112E16; http://www.amazon.com/exec/obidos/ASIN/B000112E16/icongroupinterna

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Traumatic brain injury : evaluation and litigation by Richard W. Petrocelli; ISBN: 1558341722; http://www.amazon.com/exec/obidos/ASIN/1558341722/icongroupinterna

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Traumatic Brain Injury Act of 1996 : report (to accompany H.R. 248) (SuDoc Y 1.1/8:104-652) by U.S. Congressional Budget Office; ISBN: B00010RERQ; http://www.amazon.com/exec/obidos/ASIN/B00010RERQ/icongroupinterna

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Traumatic Brain Injury Activities: Back into Life (Functional Communication Series) by Andrew K. Gruen, Lynn S. Gruen; ISBN: 0930599950; http://www.amazon.com/exec/obidos/ASIN/0930599950/icongroupinterna

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Traumatic Brain Injury and Neuorpsychological Impairment: Sensorimotor, Cognitive, Emotional and Adaptive Problems of Children and Adults by Rolland S. Parker; ISBN: 0387972390; http://www.amazon.com/exec/obidos/ASIN/0387972390/icongroupinterna

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Traumatic Brain Injury and Neuropsychological Impairment: Sensorimotor, Cognitive, Emotional, and Adaptive Problems of Children and Adults; ISBN: 3540972390; http://www.amazon.com/exec/obidos/ASIN/3540972390/icongroupinterna

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Traumatic Brain Injury in Children and Adolescents: A Sourcebook for Teachers and Other School Personnel by Janet Siantz Tyler, Mary P. Mira; ISBN: 0890798052; http://www.amazon.com/exec/obidos/ASIN/0890798052/icongroupinterna

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Traumatic Brain Injury in Children and Adolescents: Assessment and Intervention by Margaret Semrud-Clikeman (Author); ISBN: 1572306866; http://www.amazon.com/exec/obidos/ASIN/1572306866/icongroupinterna

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Traumatic brain injury in children and teens : a national guide for families (SuDoc HE 20.9208:B 76) by Janet Houston; ISBN: B000112IK8; http://www.amazon.com/exec/obidos/ASIN/B000112IK8/icongroupinterna

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Traumatic Brain Injury in Sports: An International Neuropsychological Perspective by Mark R. Lovell (Editor), et al; ISBN: 9026519613; http://www.amazon.com/exec/obidos/ASIN/9026519613/icongroupinterna

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Traumatic brain injury programs supporting long-term services in selected states : report to congressional requesters (SuDoc GA 1.13:HEHS-98-55) by U.S. General Accounting Office; ISBN: B00010XZ9C; http://www.amazon.com/exec/obidos/ASIN/B00010XZ9C/icongroupinterna

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Traumatic brain injury Quick Turn Around Project Forum : QTA-a brief analysis of a critical issue in special education (SuDoc ED 1.310/2:451633) by Joy Markowitz; ISBN:

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B000116MGO; http://www.amazon.com/exec/obidos/ASIN/B000116MGO/icongroupinterna •

Traumatic Brain Injury Rehabilitation: Children and Adolescents by Mark Ylvisaker (Editor); ISBN: 0750699728; http://www.amazon.com/exec/obidos/ASIN/0750699728/icongroupinterna

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Traumatic Brain Injury Rehabilitation: Practical Vocational, Neuropsychological, and Psychotherapy Interventions by Robert T. Fraser (Editor), David Charles Clemmons (Editor); ISBN: 0849333156; http://www.amazon.com/exec/obidos/ASIN/0849333156/icongroupinterna

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Traumatic Brain Injury Rehabilitation: Services, Treatments and Outcomes by A. Tennant (Editor), et al; ISBN: 0412489708; http://www.amazon.com/exec/obidos/ASIN/0412489708/icongroupinterna

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Traumatic brain injury what the teacher needs to know (SuDoc ED 1.310/2:341172) by Betty Pieper; ISBN: B00010EC7G; http://www.amazon.com/exec/obidos/ASIN/B00010EC7G/icongroupinterna

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Traumatic Brain Injury: A Family Guide to Assisting in Speech, Language, and Cognitive Rehabilitation by Roselyn Cera, et al; ISBN: 9994158813; http://www.amazon.com/exec/obidos/ASIN/9994158813/icongroupinterna

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Traumatic Brain Injury: Associated Speech, Language, and Swallowing Disorders by B. E. Murdoch, Deborah G., Phd Theodoros; ISBN: 0769300170; http://www.amazon.com/exec/obidos/ASIN/0769300170/icongroupinterna

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Traumatic Brain Injury: Clinical, Social and Rehabilitational Aspects by B.G. Deelman, et al; ISBN: 9026510829; http://www.amazon.com/exec/obidos/ASIN/9026510829/icongroupinterna

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Traumatic Brain Injury: Mechanisms of Damage, Assessment, Intervention, and Outcome by Erin D. Bigler (Editor); ISBN: 0890792011; http://www.amazon.com/exec/obidos/ASIN/0890792011/icongroupinterna

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Traumatic Brain Injury: Methods for Clinical and Forensic Neuropsychiatric Assessment by Jr., Robert P. Granacher, Robert P. Granacher; ISBN: 0849314291; http://www.amazon.com/exec/obidos/ASIN/0849314291/icongroupinterna

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Traumatic Brain Injury: Pathophysiology and Neuropsychological Evaluation by R. Reitan; ISBN: 0934515069; http://www.amazon.com/exec/obidos/ASIN/0934515069/icongroupinterna

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Traumatic Brain Injury: Recovery and Rehabilitation by Ralph M. Reitan, Deborah Wolfson; ISBN: 0934515077; http://www.amazon.com/exec/obidos/ASIN/0934515077/icongroupinterna

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Traumatic Brain Injury: Rehabilitation for Everyday Living by Jennie Ponsford, et al; ISBN: 0863773761; http://www.amazon.com/exec/obidos/ASIN/0863773761/icongroupinterna

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Traumatic Brain Injury: Rehabilitation for Speech-Language Pathologists by Jeffrey N. Pierce, et al; ISBN: 0750696508; http://www.amazon.com/exec/obidos/ASIN/0750696508/icongroupinterna

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Traumatic Brain Injury: Rehabilitative Treatment and Case Management, Second Edition by Mark J. Ashley (Editor); ISBN: 0849313627; http://www.amazon.com/exec/obidos/ASIN/0849313627/icongroupinterna

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Traumatic Brain Injury: Vocational Rehabilitation Job Placement Models by Robert T. Fraser, et al; ISBN: 1878205226; http://www.amazon.com/exec/obidos/ASIN/1878205226/icongroupinterna

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Traumatic head injury exercise : instructor's copy; Traumatic head injury exercise : problem booklet (SuDoc I 28.2:B 39/trau./inst.) by U.S. Dept of Interior; ISBN: B0001057VG; http://www.amazon.com/exec/obidos/ASIN/B0001057VG/icongroupinterna

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Traumatic Head Injury in Children by Sarah H. Broman (Editor), et al; ISBN: 019509428X; http://www.amazon.com/exec/obidos/ASIN/019509428X/icongroupinterna

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Vocational Evaluation & Traumatic Brain Injury: A Procedural Manual by Stephen W. Thomas; ISBN: 0916671941; http://www.amazon.com/exec/obidos/ASIN/0916671941/icongroupinterna

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Vocational Rehabilitation: For Persons With Traumatic Brain Injury by Paul Wehman, et al; ISBN: 0834201356; http://www.amazon.com/exec/obidos/ASIN/0834201356/icongroupinterna

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What Legislators Need to Know About Traumatic Brain Injuries by Barbara Wright; ISBN: 1555166601; http://www.amazon.com/exec/obidos/ASIN/1555166601/icongroupinterna

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Working With Behavior Disorders: Strategies for Traumatic Brain Injury Rehabilitation by Craig S. Persel, et al; ISBN: 0127845860; http://www.amazon.com/exec/obidos/ASIN/0127845860/icongroupinterna

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

The Educational Needs of Children with Traumatic Brain Injury Source: Children with Traumatic Brain Injury: A Parent's Guide. Bethesda, MD. Woodbine House Special Needs Collection. Contact: Available from Woodbine House. 6510 Bells Mill Rd., Bethesda, MD 20817. 301897-3570; 800-843-7323. Web site: www.woodbinehouse.com. ISBN: 0-933149-99-9. pp 294-349. PRICE: full text available at $17.95 plus shipping and handling. Summary: In this chapter of Children with Traumatic Brain Injury: A Parent's Guide, the authors discuss how the effects of traumatic brain injury (TBI), including psychosocial, emotional, and cognitive functioning impacts a child's ability to succeed in school. The chapter discusses the laws that govern special educational services (IDEA and ADA), private and public assessment and interpretation, parent and educator roles, and assistance for children who may not be eligible under IDEA.

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AAC and Traumatic Brain Injury: Influence of Cognition on System Design and Use Source: in Beukelman, D.R.; Yorkston, K.M.; Reichle, J., eds. Augmentative and Alternative Communication for Adults with Acquired Neurologic Disorders. Baltimore, MD: Paul H. Brookes Publishing Co. 2000. p. 271-304. Contact: Available from Paul H. Brookes Publishing Co. P.O. Box 10624, Baltimore, MD 21285. (800) 638-3775. Fax (410) 337-8539. Website: www.brookespublishing.com. PRICE: $42.00 plus shipping and handling. ISBN: 1557664730. Summary: The loss of speech in adulthood due to acquired neurologic disorders causes a person to confront enormous life changes. This chapter on the use of augmentative and alternative communication (AAC) strategies for people with traumatic brain injury (TBI) is from a textbook that explores the challenges these adults face during their transition, whether gradual or immediate, from speaking to using AAC. People with a TBI may experience such severe neurogenic communication disorders that they are unable to meet their communication needs through natural speech alone. Many people use AAC systems sometime during the recovery process. In this chapter, the authors review the neuropathology of TBI, discuss the cognitive impairments and behavior issues that are commonly associated with TBI, present a theoretical framework that assists in the rehabilitation of people with TBI using AAC systems, and discuss the influence of cognition on the selection, design, and use of AAC systems. The authors discuss different types of AAC systems, assessing and remediating impairments, functional limitations, factors to consider in the configuration of AAC display, and symbol use and message formulation. The authors conclude by noting that AAC devices are getting smaller and more powerful, and they perform a variety of functions. Speech language pathologists and other rehabilitation professionals are increasingly aware of the benefits of AAC for people with TBI and are incorporating AAC into treatment plans for individuals at all stages of recovery. 2 tables. 70 references.

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Assessment of Mild-to-Moderate Traumatic Brain Injury Source: in Green, B.S.; Sevens, K.M.; Wolfe, T.D.W. Mild Traumatic Brain Injury: A Therapy and Resource Manual. San Diego, CA: Singular Publishing Group, Inc. 1998. p. 19-60. 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: $49.95 plus shipping and handling. ISBN: 1565938275. Summary: This chapter is from a therapy and reference manual created in response to the unique needs of adolescents and adults who have sustained mild to moderate traumatic brain injuries (MTBI). The authors focus on providing practical suggestions for developing individualized therapy tasks to promote a client's successful return to the demands of the home, school, or work environment. This chapter addresses the assessment of MTBI. Topics include neuropsychological evaluation and assessment considerations, the importance of an integrated assessment, test administration, complex attention, memory skills, verbal communication skills, written communication skills, verbal information processing skills, written information processing skills, executive functioning skills, reasoning skills, and mathematical skills. A final section covers preparing the cognitive language evaluation report, including analyzing test scores, interpreting supplemental information, and sharing assessment results. The chapter concludes with extensive appendices, including client interview questionnaires, sample

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evaluation segments, vocational recommendations, and publisher and purchasing information for standardized tests. 10 references. •

Psychosocial Effects of Traumatic Brain Injury Source: Austin, TX: PRO-ED, Inc. 1999. Traumatic Brain Injury in Children and Adolescents: A Sourcebook for Teachers and Other School Personnel, Second Edition. ISBN:0-89079-805-2. (5)29-38. Contact: Available from PRO-ED, Inc. 8700 Shoal Creek Boulevard, Austin, TX 787576897. (800) 897-3202; Fax (800) 397-7633. Web site: http://www.proedinc.com. PRICE: $30.00 plus shipping and handling for full text. Summary: This fifth chapter of the second edition of the teacher's sourcebook, Traumatic Brain Injury in Children and Adolescents, discusses types of psychosocial problems; age considerations; issues in adolescent TBI, and the school's role in psychosocial outcome.

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Immediate and Long-Term Effects of Traumatic Brain Injury Source: Austin, TX: PRO-ED, Inc. 1999. Traumatic Brain Injury in Children and Adolescents: A Sourcebook for Teachers and Other School Personnel, Second Edition. ISBN:0-89079-805-2. (4)15-28. Contact: Available from PRO-ED, Inc. 8700 Shoal Creek Boulevard, Austin, TX 787576897. (800) 897-3202; Fax (800) 397-7633. Web site: http://www.proedinc.com. PRICE: $30.00 plus shipping and handling for full text. Summary: This fourth chapter of the second edition of the teacher's sourcebook, Traumatic Brain Injury in Children and Adolescents, discusses the neuropathology; initial and long- term effects, including language, cognitive, sensory, and emotional; and characteristics of traumatic brain injury (TBI). A case study is included.

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Facts About Traumatic Brain Injury in Children and Adolescents Source: Austin, TX: PRO-ED, Inc. 1999. Traumatic Brain Injury in Children and Adolescents: A Sourcebook for Teachers and Other School Personnel, Second Edition. ISBN:0-89079-805-2. (2)3-8. Contact: Available from PRO-ED, Inc. 8700 Shoal Creek Boulevard, Austin, TX 787576897. (800) 897-3202; Fax (800) 397-7633. Web site: http://www.proedinc.com. PRICE: $30.00 plus shipping and handling for full text. Summary: This second chapter of the second edition of the teacher's sourcebook, Traumatic Brain Injury in Children and Adolescents, discusses incidents of traumatic brain injury (TBI) among children; levels of severity of TBI; and causes and risk factors of TBI.

Directories In addition to the references and resources discussed earlier in this chapter, a number of directories relating to traumatic brain injury have been published that consolidate

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information across various sources. The Combined Health Information Database lists the following, which you may wish to consult in your local medical library:10 •

Directory of Speech-Language Pathology Assessment Instruments Source: Rockville, MD: American Speech-Language-Hearing Association (ASHA). 1996. 402 p. Contact: Available from American Speech-Language-Hearing Association (ASHA). Product Sales, 10801 Rockville Pike, Rockville, MD 20852. (888) 498-6699. TTY (301) 8970157. Website: www.asha.org. PRICE: $30.00 plus shipping and handling. Item Number 0111968. Summary: This directory provides speech-language pathologists with a comprehensive reference on assessment tools used to evaluate the speech and language abilities of individuals across the life span. Assessment instruments are categorized according to areas of practice in speech-language pathology. Screening instruments are included with other tests in each category. Tests are categorized in the following areas: spoken language assessment, written language assessment, cognitive communication assessment (including dementia and traumatic brain injury), articulation and phonology assessment, fluency assessment, voice assessment, swallowing and oral motor assessment, test batteries, related tests, and developmental scales. For each assessment instrument, the directory provides title, authors, year (most recent revision), source (companies that sell the test; the publisher is listed first, then others in alphabetical order), age range, administration time in minutes, availability in other languages, availability of computerized scoring, a brief description, reference to review of the instrument in an ASHA publication, and the date the entry was reviewed or updated by the publisher. The directory concludes with a list of the titles of all tests within each category, an alphabetized list of the titles of all test materials, and an alphabetized listing of publishers with addresses and telephone numbers.

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You will need to limit your search to “Directory” and “traumatic brain injury” using the "Detailed Search" option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find directories, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Select your preferred language and the format option “Directory.” Type “traumatic brain injury” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months.

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CHAPTER 7. MULTIMEDIA ON TRAUMATIC BRAIN INJURY Overview In this chapter, we show you how to keep current on multimedia sources of information on traumatic brain injury. We start with sources that have been summarized by federal agencies, and then show you how to find bibliographic information catalogued by the National Library of Medicine.

Video Recordings An excellent source of multimedia information on traumatic brain injury is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “traumatic brain injury” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find video productions, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Videorecording (videotape, videocassette, etc.).” Type “traumatic brain injury” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on traumatic brain injury: •

Speech Production Disorders Following Traumatic Brain Injury Source: Tucson, AZ: National Center for Neurogenic Communication Disorders. 1993. (videocassette and handout). Contact: Available from National Center for Neurogenic Communication Disorders. Telerounds Coordinator, Building 71, Room 500, University of Arizona, Tucson, AZ 85721. (520) 621-1819 or (520) 621-1472. PRICE: $25.00. Summary: In this telerounds program, speech production disorders and neural lesions are described for a group of individuals with traumatic brain injury (TBI). The neural lesions are interpreted in terms of their possible relations to the speech disorders and the proposed neural mechanisms of speech production. The program also discusses the associated research and clinical implications. The handout provided with the videotape includes an abstract, a list of objectives, a brief outline of the program, a reference list, and an evaluation form for viewers to complete and return. 31 references. (AA-M).

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CHAPTER 8. PERIODICALS AND NEWS ON TRAUMATIC BRAIN INJURY Overview In this chapter, we suggest a number of news sources and present various periodicals that cover traumatic brain injury.

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

Recovery time increases with multiple sports-related traumatic brain injuries Source: Reuters Medical News Date: November 18, 2003

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Paratroopers at risk for head injury: study Source: Reuters Health eLine Date: November 03, 2003

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Hypothermia may improve outcome of traumatic brain injury Source: Reuters Industry Breifing Date: June 10, 2003

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Fall-related traumatic brain injury deaths up in the elderly Source: Reuters Medical News Date: December 06, 2002

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Full bed rest after mild traumatic brain injury not recommended Source: Reuters Medical News Date: August 16, 2002

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Serum cleaved tau may aid ED workup of patients with closed head injury Source: Reuters Medical News Date: March 29, 2002

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Community rehabilitation beneficial after severe traumatic brain injury Source: Reuters Medical News Date: February 14, 2002

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Against guidelines, hyperventilation continues for traumatic brain injury Source: Reuters Medical News Date: February 14, 2002

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Experimental repetitive head injury speeds onset of Alzheimer's disease Source: Reuters Medical News Date: January 17, 2002

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Head injury linked to a risk of future depression Source: Reuters Health eLine Date: January 15, 2002

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Clinical pathways improve care of patients with traumatic brain injury Source: Reuters Medical News Date: September 04, 2001

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Patients with head injury should be assessed before resuming driving Source: Reuters Medical News Date: June 01, 2001

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Driving shortly after head injury may be unsafe Source: Reuters Health eLine Date: June 01, 2001

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Paging system aids memory after head injury or stroke Source: Reuters Medical News Date: April 19, 2001

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Pager system aids memory after head injury, stroke Source: Reuters Health eLine Date: April 18, 2001

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Creatine supplementation may be neuroprotective in traumatic brain injury Source: Reuters Industry Breifing Date: November 21, 2000

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Women have poorer outcomes than men after traumatic brain injury Source: Reuters Medical News Date: November 06, 2000

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Blood alcohol level at time of traumatic brain injury predicts long-term mortality Source: Reuters Medical News Date: November 03, 2000

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Home rehabilitation helps head injury patients Source: Reuters Health eLine Date: June 21, 2000

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Home rehabilitation as good as in-hospital treatment for traumatic brain injury Source: Reuters Medical News Date: June 21, 2000

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Method predicts memory restoration in head injury patients Source: Reuters Health eLine Date: March 29, 2000

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Head injury rehabilitation outcome assessment tool found reliable Source: Reuters Medical News Date: December 31, 1999

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New drug may halt brain damage after head injury Source: Reuters Health eLine Date: September 17, 1999

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Serum S-100 protein validated as marker of traumatic brain injury Source: Reuters Medical News Date: September 13, 1999

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Head injuries among athletes can impair cognitive performance Source: Reuters Medical News Date: September 08, 1999

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Athletes' head injuries impair intellectual performance Source: Reuters Health eLine Date: September 07, 1999

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NIH calls for better assessment, management of traumatic brain injury Source: Reuters Medical News Date: October 29, 1998

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Severe traumatic brain injury in children significant risk factor for psychiatric disorders Source: Reuters Medical News Date: July 23, 1998

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Disorders Similar In Children With And Without Traumatic Brain Injury In Outpatient Psych Setting Source: Reuters Medical News Date: February 27, 1997

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Hypothermia After Traumatic Brain Injury Improves Outcome Source: Reuters Medical News Date: February 20, 1997

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Botulinum Toxin Improves Upper Extremity Spasticity In Traumatic Brain Injury Patients Source: Reuters Medical News Date: October 31, 1996 The NIH

Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “traumatic brain injury” (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 “traumatic brain injury” (or synonyms). If you know the name of a company that is relevant to traumatic brain injury, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/. BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “traumatic brain injury” (or synonyms).

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Newsletter Articles Use the Combined Health Information Database, and limit your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter Article.” Type “traumatic brain injury” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months. The following is a typical result when searching for newsletter articles on traumatic brain injury: •

Memory and Disability: What Is Memory? Source: Wellspring Currents. [Newsletter] Number 1: 1-3, 5, 7. Summer 1991. Contact: Available from Wellspring Currents. 179 West Washington, Suite 360, Chicago, IL. 60602. (312) 201-9696. PRICE: Call for price information. Summary: Memory impairment is a common complaint of patients who have psychological problems such as depression or those who have primary neurologic disorders such as Alzheimer's disease, Parkinson's disease, and traumatic brain injury. This newsletter article discusses what is currently understood about how normal memory operates and the influence of aging on memory. Also discussed are the validity, use, and misuse of memory and mental status tests in guardianship and residential placement of memory impaired individuals.

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

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CHAPTER 9. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.

U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for traumatic brain injury. 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).

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Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.

Mosby’s Drug Consult Mosby’s Drug Consult database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/.

PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee.

Researching Orphan Drugs Although the list of orphan drugs is revised on a daily basis, you can quickly research orphan drugs that might be applicable to traumatic brain injury 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 “traumatic brain injury” (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

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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 traumatic brain injury: •

Dimethyl sulfoxide http://www.rarediseases.org/nord/search/nodd_full?code=238

•

Enadoline hydrochloride http://www.rarediseases.org/nord/search/nodd_full?code=817

If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.

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APPENDICES

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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.

NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute11: •

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

•

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/

11

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

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•

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

•

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

•

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

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

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

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

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

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

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

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

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

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

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

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

•

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.12 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:13 •

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

•

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

•

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

•

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

•

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

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

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

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

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

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

•

MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html

12

Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 13 See http://www.nlm.nih.gov/databases/databases.html.

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•

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

•

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

The NLM Gateway14 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.15 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “traumatic brain injury” (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 26157 1005 918 25 38 28143

HSTAT16 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.17 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.18 Simply search by “traumatic brain injury” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

14

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

15

The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 16 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 17 18

The HSTAT URL is http://hstat.nlm.nih.gov/.

Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.

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Coffee Break: Tutorials for Biologists19 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.20 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.21 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.

Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •

CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.

•

Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.

19 Adapted 20

from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.

The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 21 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.

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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 traumatic brain injury 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 traumatic brain injury. 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 traumatic brain injury. 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 “traumatic brain injury”:

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Accidents http://www.nlm.nih.gov/medlineplus/accidents.html Aneurysms http://www.nlm.nih.gov/medlineplus/aneurysms.html Bone Diseases http://www.nlm.nih.gov/medlineplus/bonediseases.html Brain Cancer http://www.nlm.nih.gov/medlineplus/braincancer.html Brain Diseases http://www.nlm.nih.gov/medlineplus/braindiseases.html Cerebral Palsy http://www.nlm.nih.gov/medlineplus/cerebralpalsy.html Child Safety http://www.nlm.nih.gov/medlineplus/childsafety.html Fractures http://www.nlm.nih.gov/medlineplus/fractures.html Head and Brain Injuries http://www.nlm.nih.gov/medlineplus/headandbraininjuries.html Hip Injuries and Disorders http://www.nlm.nih.gov/medlineplus/hipinjuriesanddisorders.html Neck Disorders and Injuries http://www.nlm.nih.gov/medlineplus/neckdisordersandinjuries.html Osteogenesis Imperfecta http://www.nlm.nih.gov/medlineplus/osteogenesisimperfecta.html Osteoporosis http://www.nlm.nih.gov/medlineplus/osteoporosis.html Peripheral Nerve Disorders http://www.nlm.nih.gov/medlineplus/peripheralnervedisorders.html Rehabilitation http://www.nlm.nih.gov/medlineplus/rehabilitation.html Spinal Cord Injuries http://www.nlm.nih.gov/medlineplus/spinalcordinjuries.html Sports Injuries http://www.nlm.nih.gov/medlineplus/sportsinjuries.html Sports Safety http://www.nlm.nih.gov/medlineplus/sportssafety.html Stroke http://www.nlm.nih.gov/medlineplus/stroke.html

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Within the health topic page dedicated to traumatic brain injury, the following was listed: •

General/Overviews Facts about Concussion and Brain Injury and Where to Get Help Source: National Center for Injury Prevention and Control http://www.cdc.gov/doc.do?id=0900f3ec8006c289 Head Injuries: What to Watch for Afterward Source: American Academy of Family Physicians http://familydoctor.org/084.xml

•

Diagnosis/Symptoms Computed Tomography (CT)-Head Source: American College of Radiology, Radiological Society of North America http://www.radiologyinfo.org/content/ct_of_the_head.htm Functional MR Imaging (fMRI) - Brain Source: American College of Radiology, Radiological Society of North America http://www.radiologyinfo.org/content/functional_mr.htm Head Trauma Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=FA00008

•

Treatment First Aid for Head Injuries Source: National Institute for Occupational Safety and Health http://www.cdc.gov/nasd/docs/d000801-d000900/d000815/d000815.html What Is Neurosurgery? http://www.nlm.nih.gov/medlineplus/tutorials/whatisneurosurgeryloader.html

•

Specific Conditions/Aspects Brain Injuries and Mass Trauma Events Source: National Center for Injury Prevention and Control http://www.cdc.gov/masstrauma/factsheets/public/brain_injuries.htm Brain Pain: Recognizing a Subdural Hematoma Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=BN00015 Cerebral Hypoxia (Anoxia) Source: National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/health_and_medical/disorders/anoxia_doc.htm Coma, Including Persistent Vegetative State Source: National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/health_and_medical/disorders/coma_doc.htm Concussion Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=DS00320

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Intracranial Hematoma Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=DS00330 JAMA Patient Page: Concussion in Sports Source: American Medical Association http://www.medem.com/medlb/article_detaillb.cfm?article_ID=ZZZMFGAA9ND &sub_cat=187 Traumatic Brain Injury: Cognitive and Communication Disorders Source: National Institute on Deafness and Other Communication Disorders http://www.nidcd.nih.gov/health/voice/tbrain.asp Traumatic Brain Injury: No One Pathway to Recovery Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=BN00005 •

Children Bump on the Head: When Is It Serious? Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=HQ00763 Concussions Source: Nemours Foundation http://kidshealth.org/kid/ill_injure/aches/concussion.html Head Injuries Source: Nemours Foundation http://kidshealth.org/parent/firstaid_safe/emergencies/head_injury.html JAMA Patient Page: Inflicted Brain Injury in Children Source: American Medical Association http://www.medem.com/medlb/article_detaillb.cfm?article_ID=ZZZ4SS4F0JD&s ub_cat=187 Shaken Baby Syndrome Source: National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/health_and_medical/disorders/shakenbaby.htm

•

From the National Institutes of Health Traumatic Brain Injury: Hope Through Research Source: National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/health_and_medical/pubs/TBI.htm

•

Latest News Fetal Monitoring Fails to Detect Brain Injury Source: 03/26/2004, Reuters Health http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_16794 .html Heavy Social Drinkers Show Brain Damage Source: 04/14/2004, Reuters Health http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_17143

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.html •

Law and Policy Bicycle Helmet Use Laws Source: National Highway Traffic Safety Administration http://www.nhtsa.dot.gov/people/injury/New-factsheet03/BicycleHelmetUse.pdf

•

Organizations Brain Injury Association http://www.biausa.org/Pages/home.html National Center for Injury Prevention and Control http://www.cdc.gov/ncipc/ National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/

•

Prevention/Screening Heads Up: Preventing Brain Injuries Source: National Center for Injury Prevention and Control http://www.cdc.gov/doc.do?id=0900f3ec8000d8c9 JAMA Patient Page: Protecting against Head Injuries Source: American Medical Association http://www.medem.com/medlb/article_detaillb.cfm?article_ID=ZZZ8ZI10NAC& sub_cat=366

•

Research Knocking Noggins Source: Society for Neuroscience http://web.sfn.org/content/Publications/BrainBriefings/knocking.html Life and Death of a Neuron Source: National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/health_and_medical/pubs/NINDS_Neuron.htm

•

Statistics Traumatic Brain Injury Facts and Statistics Source: National Center for Injury Prevention and Control http://www.cdc.gov/doc.do?id=0900f3ec800081d7

•

Teenagers Concussions Source: Nemours Foundation http://kidshealth.org/teen/safety/first_aid/concussions.html

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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 traumatic brain injury. 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: •

Special Populations: Traumatic Brain Injury Source: Rockville, MD: American Speech-Language-Hearing Association (ASHA). 1999. [1 p.]. Contact: Available from American Speech-Language-Hearing Association (ASHA). Product Sales, 10801 Rockville Pike, Rockville, MD 20852. (888) 498-6699. TTY (301) 8970157. Website: www.asha.org. PRICE: Single copy free. Summary: Communication disorders are among the behavioral disturbances that can result from traumatic brain injury (TBI). Thus, speech language pathologists and audiologists are important members of the team of health care professionals involved in the rehabilitation of these patients. This fact sheet reviews some of the statistics about people with TBI and reviews the language and communication disorders that may result from this trauma. The fact sheet notes that approximately 50,000 of the estimated two million people who have TBI each year in the U.S. have severe, persisting communication problems as a result. Left hemisphere brain damage can result in aphasia; right hemisphere damage can cause communication disorders such as problems in appropriate use of language. Hematomas and pressure-producing skull fractures can result in facial paralysis, deafness, muscle disorders, and loss of sensory function. 8 references.

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Traumatic Brain Injury: Every Parent's Fear Source: in DeFeo, A.B., ed. Parent Articles 2. San Antonio, TX: Communication Skill Builders. 1995. p. 179-180. Contact: Available from Communication Skill Builders. Customer Service, 555 Academic Court, San Antonio, TX 78204-2498. (800) 211-8378; Fax (800) 232-1223. PRICE: $55.00 plus shipping and handling. Order Number 076-163-0732. Summary: In this fact sheet, from a communication skills book for parents, a parent of a child with a traumatic brain injury (TBI) discusses the emotions and psychological factors that may affect the parents of children with TBI. Topics covered include the author's family's story, coping immediately after the trauma occurs, later recovery, speech and language re-development, psychosocial concerns as the child progresses, the

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role of speech language therapy, dealing with the rehabilitation and insurance communities, and the need for parents to find their own support network. The author encourages parents to educate themselves, to draw on other parents for support, and to act as their child's advocate. •

After Traumatic Brain Injury: Helping Someone You Love During Early Rehabilitation Source: San Bruno, CA: Krames-Staywell. 1997. 16 p. Contact: Available from Krames-Staywell. Order Department, 1100 Grundy Lane, San Bruno, CA 94066-9821. (800) 333-3032. Fax (650) 244-4512. Website: www.krames.com. PRICE: $1.50 each; bulk copies available. Order number 1812-TXDT. Summary: This booklet helps families and caregivers understand their role as a family member undergoes rehabilitation after traumatic brain injury (TBI). The booklet emphasizes that recovering from brain injury is a lifelong process. Topics covered include the members of the patient rehabilitation team, the role of the family member, the physiology of the brain, how brain injury happens, the different types of brain injury (tearing, bleeding, swelling), how thinking skills are affected, strategies for helping patients with their thinking skills (to improve memory, link ideas, relearn language), strategies for help with the patient's senses (to regain balance, address problems with sight or sound, and deal with time), behavioral changes that may accompany brain injury and how to deal with them (to handle feelings, control agitation, and regain social skills), how to handle other physical problems (to improve posture and motion, reduce muscle and joint problems, reduce swallowing problems, and control seizures), and strategies to support family relationships. The booklet offers practical strategies for family members to apply in everyday activities. The brochure is filled with line drawings of families in various settings. The tollfree number of the National Brain Injury Association (800-444-6443) is provided as a resource.

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Traumatic Brain Injury: A Guide for the Patient and Family Source: Stow, OH: Interactive Therapeutics, Inc. 1993. 61 p. Contact: Available from Interactive Therapeutics, Inc. P.O. Box 1805, Stow, OH 44224. (800) 253-5111 or (216) 688-1371; Fax (330) 923-3030; E-mail: [email protected]. PRICE: $4.50 each for 1 to 25 copies; bulk rates available. Summary: This booklet is intended to serve as an introduction to traumatic brain injury (TBI) and as a reference to other sources of information to guide patients and their families as they learn about TBI. Four sections cover brain function, TBI and how it affects the brain, what to expect during recovery and rehabilitation, and living and coping with TBI. The chapter on possible impairments from TBI includes a section on speech and language disorders, covering aphasia, communication problems, dysarthria, and apraxia of speech. The booklet concludes with an extensive glossary of terms.

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Prevalence of Traumatic Brain Injury in the United States Source: Rockville, MD: American Speech-Language-Hearing Association (ASHA), Science and Research Department. 1995. 1 p. Contact: Available from American Speech-Language-Hearing Association (ASHA). Science and Research Department. 10801 Rockville Pike, Rockville, MD 20852. (301) 8975700. PRICE: Single copy free.

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Summary: This fact sheet from the American Speech-Language Hearing Association (ASHA) provides information on the prevalence of traumatic brain injury in the United States. Topics covered include communication disorders resulting from traumatic brain injury, statistics on head trauma, the most common causes of head injuries and the most common victims, survival rates, language function and brain hemisphere, hematomas, and prognostic considerations. 5 references. •

Traumatic Brain Injury: Cognitive and Communication Disorders Source: Bethesda, MD: National Institute on Deafness and Other Communication Disorders (NIDCD), National Institutes of Health (NIH). July 1998. [4 p.]. Contact: Available from NIDCD Information Clearinghouse. 1 Communication Avenue, Bethesda, MD 20892-3456. Voice (800) 241-1044. TTY (800) 241-1055. Fax (301) 907-8830. E-mail: [email protected]. Website: www.nidcd.nih.gov. PRICE: Single copy free. NIH Publication Number 98-4315. Summary: This fact sheet provides basic information about traumatic brain injury (TBI), defined as sudden physical damage to the brain. The fact sheet outlines the possible causes of TBI, and the resulting brain injuries. The author notes that major speech and language areas often receive damage in TBI, resulting in communication difficulties. Other problems due to TBI can be voice, swallowing, walking, balance, and coordination difficulties, as well as changes in the ability to smell and in memory and cognitive (thinking) skills. The fact sheet reports some statistics about who suffers from TBI, and outlines more specifically the cognitive and communication problems that can result from TBI. The fact sheet also briefly considers assessment of these cognitive and communication problems, as well as treatment options. Therapy usually focuses on regaining lost skills as well as on learning ways to compensate for abilities that have been permanently changed because of the brain injury. The fact sheet concludes with a brief description of current research efforts in this area, and a listing of organizations through which readers can get additional information. 1 figure.

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Traumatic Brain Injury Source: in DeFeo, A.B., ed. Parent Articles 2. San Antonio, TX: Communication Skill Builders. 1995. p. 145-148. Contact: Available from Communication Skill Builders. Customer Service, 555 Academic Court, San Antonio, TX 78204-2498. (800) 211-8378; Fax (800) 232-1223. PRICE: $55.00 plus shipping and handling. Order Number 076-163-0732. Summary: This fact sheet, from a communication skills book for parents, provides information on traumatic brain injury (TBI). The authors outline the cognitivecommunicative problems that can result from TBI, including attention problems, information-processing problems, the lack of vocabulary development, hyperverbal speech, tangential speech, word-finding problems, poor social language skills, nonverbal or motor speech problems, delayed language development, and memory problems. The authors also provides specific suggestions for families who want to help their child who is struggling with TBI-related communication problems. The authors encourage parents to incorporate these suggestions into everyday routines and to act as their child's advocate. 1 reference.

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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 “traumatic brain injury” (or synonyms). The following was recently posted: •

Sixth ACCP Consensus Conference on Antithrombotic Therapy Source: American College of Chest Physicians - Medical Specialty Society; 2001 January; 370 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2720&nbr=1946&a mp;string=cerebral+AND+injuries

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Society of Nuclear Medicine procedure guideline for therapy of thyroid disease with iodine-131 (sodium iodide) Source: Society of Nuclear Medicine, Inc - Medical Specialty Society; 2002 February 10; 11 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3191&nbr=2417&a mp;string=head+AND+injuries

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Specialty referral guidelines for cardiovascular evaluation and management Source: American Healthways, Inc - Public For Profit Organization; 2002; 26 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3168&nbr=2394&a mp;string=cerebral+AND+injuries

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Stroke and transient ischaemic attacks: assessment, investigation, immediate management and secondary prevention Source: Singapore Ministry of Health - National Government Agency [Non-U.S.]; 2003 March; 44 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3751&nbr=2977&a mp;string=traumatic+AND+brain+AND+injury

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Summary of policy recommendations for periodic health examinations Source: American Academy of Family Physicians - Medical Specialty Society; 1996 November (revised 2003 Aug); 13 pages http://www.guideline.gov/summary/summary.aspx?doc_id=4183&nbr=3208&a mp;string=traumatic+AND+brain+AND+injury

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Symptomatic treatment of radiation-induced xerostomia in head and neck cancer patients Source: Practice Guidelines Initiative - State/Local Government Agency [Non-U.S.]; 1998 October 15 (updated online 2002 Oct); 15 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3534&nbr=2760&a mp;string=head+AND+injury

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Systemic lupus erythematosus (SLE) Source: Finnish Medical Society Duodecim - Professional Association; 2001 April 30; Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3390&nbr=2616&a mp;string=head+AND+injuries

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The management of diabetes mellitus in the primary care setting Source: Department of Defense - Federal Government Agency [U.S.]; 1999 December; 147 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2583&nbr=1809&a mp;string=cerebral+AND+injury

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The management of priapism Source: American Urological Association, Inc. - Medical Specialty Society; 2003; Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3741&nbr=2967&a mp;string=head+AND+injury

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The role of neoadjuvant chemotherapy in locally advanced squamous cell carcinoma of the head and neck (SCCHN) (excluding nasopharynx) Source: Practice Guidelines Initiative - State/Local Government Agency [Non-U.S.]; 1996 February 15 (updated online 2003 Feb); 10 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3699&nbr=2925&a mp;string=head+AND+injuries

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The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure Source: National Heart, Lung, and Blood Institute (U.S.) - Federal Government Agency [U.S.]; 1997 (revised 2003 May 21); 22 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3744&nbr=2970&a mp;string=head+AND+injury

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Thrombocytopenia Source: Finnish Medical Society Duodecim - Professional Association; 2001 April 30; Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3393&nbr=2619&a mp;string=head+AND+injuries

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Tissue plasminogen activator (t-PA) for acute ischemic stroke Source: Daniel Freeman Memorial Hospital - Hospital/Medical Center; 1997 June (revised 2002); 10 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3422&nbr=2648&a mp;string=cerebral+AND+injuries

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Treatment for stimulant use disorders Source: Substance Abuse and Mental Health Services Administration (U.S.) - Federal Government Agency [U.S.]; 1999; Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=2540&nbr=1766&a mp;string=traumatic+AND+brain+AND+injury

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Treatment of acute myocardial infarction Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1996 May (revised 2002 Nov); 68 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3659&nbr=2885&a mp;string=head+AND+injury

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Treatment of hyperlipidaemia: aims and selection Source: Finnish Medical Society Duodecim - Professional Association; 2001 January 4 (revised 2001 November 4); Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3380&nbr=2606&a mp;string=cerebral+AND+injuries

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Ultrasonographic examinations: indications and preparation of the patient Source: Finnish Medical Society Duodecim - Professional Association; 2000 April 18 (revised 2001 October 24); Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3385&nbr=2611&a mp;string=traumatic+AND+brain+AND+injury

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Unremitting low back pain. In: North American Spine Society phase III clinical guidelines for multidisciplinary spine care specialists Source: North American Spine Society - Medical Specialty Society; 2000; 96 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2805&nbr=2031&a mp;string=head+AND+injuries

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Urinary incontinence in women Source: Finnish Medical Society Duodecim - Professional Association; 2001 January 4; Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3400&nbr=2626&a mp;string=cerebral+AND+injuries

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Use of antibiotics in adults Source: Singapore Ministry of Health - National Government Agency [Non-U.S.]; 2000 April; 78 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3434&nbr=2660&a mp;string=head+AND+injuries

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Vaginal birth after cesarean Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1994 September (revised 2002 Oct); 23 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3503&nbr=2729&a mp;string=traumatic+AND+brain+AND+injury

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VHA/DOD clinical practice guideline for the management of chronic obstructive pulmonary disease. Source: Department of Defense - Federal Government Agency [U.S.]; 1999 August; Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=2584&nbr=1810&a mp;string=head+AND+injury

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VHA/DOD clinical practice guideline for the management of major depressive disorder in adults Source: Department of Defense - Federal Government Agency [U.S.]; 1997 (updated 2000); Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=2585&nbr=1811&a mp;string=traumatic+AND+brain+AND+injury

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VHA/DoD clinical practice guideline for the management of substance use disorders Source: Department of Defense - Federal Government Agency [U.S.]; 2001 September; Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3169&nbr=2395&a mp;string=traumatic+AND+brain+AND+injury

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Viral upper respiratory infection (VURI) in adults and children Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1994 June (revised 2002 Dec); 31 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3658&nbr=2884&a mp;string=head+AND+injuries

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Wheelchair biking for the treatment of depression Source: University of Iowa Gerontological Nursing Interventions Research Center, Research Dissemination Core - Academic Institution; 2003 February; 53 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3682&nbr=2908&a mp;string=traumatic+AND+brain+AND+injury

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(1) Best practice evidence-based guideline for the appropriate prescribing of hormone replacement therapy. (2) Guideline update: hormone replacement therapy Source: Effective Practice Institute, University of Auckland - Academic Institution; 2001 May (revised information released on 2002 September 30); 185 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3107&nbr=2333&a mp;string=traumatic+AND+brain+AND+injury

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(1) Guidelines for monitoring and management of pediatric patients during and after sedation for diagnostic and therapeutic procedures. (2) Guidelines for monitoring and management of pediatric patients during and after sedation for diagnostic and therape Source: American Academy of Pediatrics - Medical Specialty Society; 1992 June (reaffirmed 1998; addendum published 2002 Oct); 10 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1775&nbr=1001&a mp;string=head+AND+injury

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(1) Part I. Guidelines for the management of severe traumatic brain injury. In: Management and prognosis of severe traumatic brain injury. (2) Update notice. Guidelines for the management of severe traumatic brain injury: cerebral perfusion pressure Source: American Association of Neurological Surgeons - Medical Specialty Society; 2000 (revised 2003); 165 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3794&nbr=3020&a mp;string=traumatic+AND+brain+AND+injury

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(1) Prevention and control of influenza. (2) Update: influenza activity-United States, 2003--04 season Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 1984 April (revised 2003 Apr; addendum released 2003 Dec); Original guideline: 36 pages; addendum: 4 pages http://www.guideline.gov/summary/summary.aspx?doc_id=4428&nbr=3342&a mp;string=cerebral+AND+injuries

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(1) Targeted tuberculin testing and treatment of latent tuberculosis infection Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 2000 June 9 (addendum released 2003 August 8); 54 pages http://www.guideline.gov/summary/summary.aspx?doc_id=4004&nbr=3134&a mp;string=head+AND+injury

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2002 national guidelines on the management of adult victims of sexual assault Source: Association for Genitourinary Medicine - Medical Specialty Society; 1999 August (revised 2002); Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3050&nbr=2276&a mp;string=head+AND+injuries

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A clinician's guide to surgical fires: how they occur, how to prevent them, how to put them out Source: ECRI - Private Nonprofit Research Organization; 2003 January; 20 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3688&nbr=2914&a mp;string=head+AND+injury

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AACE/AAES medical/surgical guidelines for clinical practice: management of thyroid carcinoma Source: American Association of Clinical Endocrinologists - Medical Specialty Society; 1997 (updated 2001 May-Jun); 19 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2848&nbr=2074&a mp;string=head+AND+injury

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AAOS clinical guideline on knee injury Source: American Academy of Family Physicians - Medical Specialty Society; 2001; 7 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2997&nbr=2223&a mp;string=head+AND+injury

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AAOS clinical guideline on shoulder pain Source: American Academy of Orthopaedic Surgeons - Medical Specialty Society; 2001; 24 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2998&nbr=2224&a mp;string=head+AND+injury

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ACC/AHA guideline update on perioperative cardiovascular evaluation for noncardiac surgery: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1996 Guidelines on Perioperati Source: American College of Cardiology Foundation - Medical Specialty Society; 1996 March 15 (revised 2002); 58 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3149&nbr=2375&a mp;string=head+AND+injury

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ACC/AHA/ESC guidelines for the management of patients with atrial fibrillation. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guide Source: American College of Cardiology Foundation - Medical Specialty Society; 2001 October; 70 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2968&nbr=2194&a mp;string=cerebral+AND+injuries

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ACC/AHA/NASPE 2002 guideline update for implantation of cardiac pacemakers and antiarrhythmia devices: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines Source: American College of Cardiology Foundation - Medical Specialty Society; 1998 April (revised 2002 Sep); 48 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3439&nbr=2665&a mp;string=cerebral+AND+injuries

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Accelerated radiotherapy for locally advanced squamous cell carcinoma of the head and neck Source: Practice Guidelines Initiative - State/Local Government Agency [Non-U.S.]; 2000 November 27 (updated online 2002 Oct); 19 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3764&nbr=2990&a mp;string=head+AND+injuries

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ACR Appropriateness Criteria™ for acute trauma to the knee Source: American College of Radiology - Medical Specialty Society; 1998 (revised 2001); 8 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3261&nbr=2487&a mp;string=head+AND+injury

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ACR Appropriateness Criteria™ for imaging recommendations for patients with dysphagia Source: American College of Radiology - Medical Specialty Society; 1998 (revised 2001); 6 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3259&nbr=2485&a mp;string=head+AND+injuries

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ACR Appropriateness Criteriatm for ataxia Source: American College of Radiology - Medical Specialty Society; 1999; 6 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2449&nbr=1675&a mp;string=cerebral+AND+injury

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ACR Appropriateness Criteriatm for atraumatic isolated headache--when to image Source: American College of Radiology - Medical Specialty Society; 1996 (revised 1999); 7 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2442&nbr=1668&a mp;string=head+AND+injuries

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ACR Appropriateness Criteriatm for cerebrovascular disease Source: American College of Radiology - Medical Specialty Society; 1996 (revised 2000); 21 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2437&nbr=1663&a mp;string=cerebral+AND+injuries

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ACR Appropriateness Criteriatm for chronic elbow pain Source: American College of Radiology - Medical Specialty Society; 1998 (revised 2001); 5 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3260&nbr=2486&a mp;string=head+AND+injury

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ACR Appropriateness Criteriatm for chronic foot pain Source: American College of Radiology - Medical Specialty Society; 1998 (revised 2002); 7 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3555&nbr=2781&a mp;string=head+AND+injury

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ACR Appropriateness Criteriatm for chronic neck pain Source: American College of Radiology - Medical Specialty Society; 1998; 12 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2429&nbr=1655&a mp;string=head+AND+injury

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ACR Appropriateness Criteriatm for dementia Source: American College of Radiology - Medical Specialty Society; 1996 (revised 1999); 9 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2445&nbr=1671&a mp;string=cerebral+AND+injuries

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ACR Appropriateness Criteriatm for epilepsy Source: American College of Radiology - Medical Specialty Society; 1996 (revised 1999); 12 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2439&nbr=1665&a mp;string=traumatic+AND+brain+AND+injury

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ACR Appropriateness Criteriatm for head trauma Source: American College of Radiology - Medical Specialty Society; 1996 (revised 1999); 18 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2444&nbr=1670&a mp;string=traumatic+AND+brain+AND+injury

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ACR Appropriateness Criteriatm for imaging of the multiply injured patient Source: American College of Radiology - Medical Specialty Society; 1995 (revised 1999); 10 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2420&nbr=1646&a mp;string=head+AND+injury

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ACR Appropriateness Criteriatm for myelopathy Source: American College of Radiology - Medical Specialty Society; 1996 (revised 1999); 11 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2443&nbr=1669&a mp;string=traumatic+AND+brain+AND+injury

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ACR Appropriateness Criteriatm for orbits, vision and visual loss Source: American College of Radiology - Medical Specialty Society; 1999; 9 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2450&nbr=1676&a mp;string=head+AND+injury

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ACR Appropriateness Criteriatm for suspected cervical spine trauma Source: American College of Radiology - Medical Specialty Society; 1995 (revised 2002); 8 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3564&nbr=2790&a mp;string=cerebral+AND+injuries

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ACR Appropriateness Criteriatm for vertigo and hearing loss Source: American College of Radiology - Medical Specialty Society; 1996 (revised 1999); 8 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2440&nbr=1666&a mp;string=head+AND+injury

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Acute pharyngitis Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1998 August (revised 2003 May); 27 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3873&nbr=3082&a mp;string=head+AND+injuries

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Acute sinusitis in adults Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1995 July (revised 2002 Dec); 30 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3673&nbr=2899&a mp;string=head+AND+injuries

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Adult low back pain Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1994 June (revised 2002 Sep); 61 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3498&nbr=2724&a mp;string=traumatic+AND+brain+AND+injury

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Amblyopia Source: American Academy of Ophthalmology - Medical Specialty Society; 1992 February (revised 2002 Oct); 25 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3546&nbr=2772&a mp;string=head+AND+injury

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American Association of Clinical Endocrinologists medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism Source: American Association of Clinical Endocrinologists - Medical Specialty Society; 1996 (revised 2002); 13 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3525&nbr=2751&a mp;string=head+AND+injuries

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American Cancer Society guidelines on nutrition and physical activity for cancer prevention: reducing the risk of cancer with healthy food choices and physical activity Source: American Cancer Society - Disease Specific Society; 2002 Mar-April; 28 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3531&nbr=2757&a mp;string=head+AND+injuries

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American Gastroenterological Association management of oropharyngeal dysphagia

medical

position

statement

on

Source: American Gastroenterological Association - Medical Specialty Society; 1998 July 24 (reviewed 2001); 3 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3067&nbr=2293&a mp;string=head+AND+injuries •

American Gastroenterological Association medical position statement on obesity Source: American Gastroenterological Association - Medical Specialty Society; 2002 September; 3 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3490&nbr=2716&a mp;string=cerebral+AND+injuries

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American Gastroenterological Association medical position statement: celiac sprue Source: American Gastroenterological Association - Medical Specialty Society; 2000 November 12 (reviewed 2001); 4 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3058&nbr=2284&a mp;string=cerebral+AND+injuries

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American Gastroenterological Association medical position statement: parenteral nutrition Source: American Gastroenterological Association - Medical Specialty Society; 2001 May 18; 4 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3056&nbr=2282&a mp;string=traumatic+AND+brain+AND+injury

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Ankle sprain Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1997 August (revised 2002 Mar); 24 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3356&nbr=2582&a mp;string=head+AND+injury

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Anticoagulants and antiplatelet agents in acute ischemic stroke: report of the Joint Stroke Guideline Development Committee of the American Academy of Neurology and the American Stroke Association (a division of the American Heart Association) Source: American Academy of Neurology - Medical Specialty Society; 2002 July; 10 pages http://www.guideline.gov/summary/summary.aspx?doc_id=4101&nbr=3146&a mp;string=cerebral+AND+injuries

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Antithrombotic and thrombolytic therapy for ischemic stroke. In: Sixth ACCP Consensus Conference on Antithrombotic Therapy Source: American College of Chest Physicians - Medical Specialty Society; 2001 January; 21 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2733&nbr=1959&a mp;string=head+AND+injury

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Antithrombotic therapy in atrial fibrillation. In: Sixth ACCP Consensus Conference on Antithrombotic Therapy Source: American College of Chest Physicians - Medical Specialty Society; 2001 January; 13 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2726&nbr=1952&a mp;string=cerebral+AND+injuries

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Antithrombotic therapy. A national clinical guideline Source: Scottish Intercollegiate Guidelines Network - National Government Agency [Non-U.S.]; 1999 March; 70 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2907&nbr=2133&a mp;string=head+AND+injury

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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=cerebral+AND+injuries

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ASHP therapeutic guidelines for nonsurgical antimicrobial prophylaxis Source: American Society of Health-System Pharmacists - Professional Association; 1999 June 15; 50 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1959&nbr=1185&a mp;string=head+AND+injury

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Aspirin for the primary prevention of cardiovascular events: recommendations and rationale Source: United States Preventive Services Task Force - Independent Expert Panel; 1996 (revised 2002 January 15); 4 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3079&nbr=2305&a mp;string=cerebral+AND+injuries

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Assessing cognitive function Source: The John A. Hartford Foundation Institute for Geriatric Nursing - Academic Institution; 2003; 25 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3508&nbr=2734&a mp;string=cerebral+AND+injuries

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Assessment and management of acute pain Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 2000 October (revised 2002 Oct); 74 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3500&nbr=2726&a mp;string=traumatic+AND+brain+AND+injury

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Assessment and management of pain Source: Registered Nurses Association of Ontario - Professional Association; 2002 November; 142 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3720&nbr=2946&a mp;string=cerebral+AND+injuries

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Assessment: Neurologic risk of immunization. Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology Source: American Academy of Neurology - Medical Specialty Society; 1999 May; 7 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2824&nbr=2050&a mp;string=cerebral+AND+injury

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Behavioral counseling in primary care to promote a healthy diet: recommendations and rationale Source: United States Preventive Services Task Force - Independent Expert Panel; 1996 (revised 2002); 20 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3494&nbr=2720&a mp;string=cerebral+AND+injuries

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Benefits and risks of controlling blood glucose levels in patients with type 2 diabetes mellitus Source: American Academy of Family Physicians - Medical Specialty Society; 1999 April; 39 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2377&nbr=1603&a mp;string=cerebral+AND+injuries

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Cancer pain Source: Singapore Ministry of Health - National Government Agency [Non-U.S.]; 2003 March; 88 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3748&nbr=2974&a mp;string=traumatic+AND+brain+AND+injury

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Cardiovascular disease in women: a guide to risk factor screening, prevention and management Source: Brigham and Women's Hospital (Boston) - Hospital/Medical Center; 2002; 15 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3487&nbr=2713&a mp;string=cerebral+AND+injuries

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Changing concepts of sudden infant death syndrome: implications for infant sleeping environment and sleep position Source: American Academy of Pediatrics - Medical Specialty Society; 2000 March; 7 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2768&nbr=1994&a mp;string=cerebral+AND+injuries

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Chemotherapy and biotherapy: guidelines and recommendations for practice Source: Oncology Nursing Society - Professional Association; 2001; 226 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3209&nbr=2435&a mp;string=traumatic+AND+brain+AND+injury

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Clinical policy: critical issues in the evaluation and management of patients presenting to the emergency department with acute headache Source: American College of Emergency Physicians - Medical Specialty Society; 2002; 15 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3298&nbr=2524&a mp;string=head+AND+injuries

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Clinical practice guideline for post-deployment health evaluation and management Source: Department of Defense - Federal Government Agency [U.S.]; 2000 September (revised 2001 Dec); Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3223&nbr=2449&a mp;string=head+AND+injury

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Clinical practice guideline: diagnosis and evaluation of the child with attentiondeficit/hyperactivity disorder Source: American Academy of Pediatrics - Medical Specialty Society; 2000 May; 13 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2280&nbr=1506&a mp;string=cerebral+AND+injuries

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Clinical practice guideline: treatment of the school-aged child with attentiondeficit/hyperactivity disorder Source: American Academy of Pediatrics - Medical Specialty Society; 2001 October; 12 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3072&nbr=2298&a mp;string=cerebral+AND+injuries

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Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult Source: American College of Critical Care Medicine - Professional Association; 1995 (revised 2002); 23 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3171&nbr=2397&a mp;string=traumatic+AND+brain+AND+injury

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Congenital syphilis. Sexually transmitted diseases treatment guidelines 2002 Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 1993 (revised 2002 May 10); 3 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3234&nbr=2460&a mp;string=head+AND+injury

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Criteria for shoulder surgery Source: Washington State Department of Labor and Industries - State/Local Government Agency [U.S.]; 1999 (revised 2002); 4 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3424&nbr=2650&a mp;string=head+AND+injury

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Determination of cervical spine stability in trauma patients (update of the 1997 EAST cervical spine clearance document) Source: Eastern Association for the Surgery of Trauma - Professional Association; 2000; 9 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2623&nbr=1849&a mp;string=traumatic+AND+brain+AND+injury

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Diagnosis and management of asthma Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1994 August (revised 2003 May); 49 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3874&nbr=3083&a mp;string=cerebral+AND+injuries

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Diagnosis and management of attention deficit hyperactivity disorder in primary care for school age children and adolescents Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1997 January (revised 2003 Mar); 66 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3761&nbr=2987&a mp;string=cerebral+AND+injuries

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Diagnosis and management of epilepsy in adults. A national clinical guideline Source: Scottish Intercollegiate Guidelines Network - National Government Agency [Non-U.S.]; 2003 April; 49 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3737&nbr=2963&a mp;string=cerebral+AND+injuries

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Diagnosis and management of headache Source: National Committee on Neuroscience (Singapore) - National Government Agency [Non-U.S.]; 2000 November; 25 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2838&nbr=2064&a mp;string=head+AND+injuries

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Diagnosis and treatment of first metatarsophalangeal joint disorders Source: American College of Foot and Ankle Surgeons - Medical Specialty Society; 2003 May-June; 43 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3849&nbr=3064&a mp;string=head+AND+injury

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Diagnosis and treatment of otitis media in children Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1995 May (revised 2002 Dec); 28 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3667&nbr=2893&a mp;string=cerebral+AND+injuries

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Diagnosis of chest pain Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1995 July (revised 2002 Oct); 50 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3674&nbr=2900&a mp;string=cerebral+AND+injuries

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Disorders of the elbow Source: Work Loss Data Institute - Public For Profit Organization; 2003; 78 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3800&nbr=3026&a mp;string=head+AND+injury

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Disorders of the neck and upper back Source: Work Loss Data Institute - Public For Profit Organization; 2003; 109 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3803&nbr=3030&a mp;string=head+AND+injury

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Early management of patients with a head injury. A national clinical guideline Source: Scottish Intercollegiate Guidelines Network - National Government Agency [Non-U.S.]; 2000 August; 43 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2912&nbr=2138&a mp;string=traumatic+AND+brain+AND+injury

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Essential hypertension Source: University of Michigan Health System - Academic Institution; 1997 (revised 2002 Aug); 14 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3539&nbr=2765&a mp;string=cerebral+AND+injuries

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Evaluating excessive sleepiness in the older adult Source: The John A. Hartford Foundation Institute for Geriatric Nursing - Academic Institution; 2003; 32 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3505&nbr=2731&a mp;string=cerebral+AND+injuries

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Evidence based clinical practice guideline for management of children with mild traumatic head injury Source: Cincinnati Children's Hospital Medical Center - Hospital/Medical Center; 2000; 9 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2162&nbr=1388&a mp;string=traumatic+AND+brain+AND+injury

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Evidence based clinical practice guideline for medical management of first unprovoked seizure in children 2 to 18 years of age Source: Cincinnati Children's Hospital Medical Center - Hospital/Medical Center; 1999 June 28 (revised 2002 July 1); 8 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3526&nbr=2752&a mp;string=head+AND+injury

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Evidence-based clinical practice guideline. Neonatal skin care Source: Association of Women's Health, Obstetric, and Neonatal Nurses - Professional Association; 2001 January; 54 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2929&nbr=2155&a mp;string=head+AND+injury

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Evidence-based practice guidelines for interventional techniques in the management of chronic spinal pain Source: American Society of Interventional Pain Physicians - Medical Specialty Society; 2003; 79 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3598&nbr=2824&a mp;string=cerebral+AND+injury

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Evidence-based protocol. Individualized music Source: University of Iowa Gerontological Nursing Interventions Research Center, Research Dissemination Core - Academic Institution; 1996 (revised 2001 Feb); 35 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3073&nbr=2299&a mp;string=cerebral+AND+injuries

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Evidence-based protocol. Wandering Source: University of Iowa Gerontological Nursing Interventions Research Center, Research Dissemination Core - Academic Institution; 2002 March; 45 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3250&nbr=2476&a mp;string=cerebral+AND+injuries

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Exercise prescription for older adults with osteoarthritis pain: consensus practice recommendations Source: American Geriatrics Society - Medical Specialty Society; 2001 June; 16 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3188&nbr=2414&a mp;string=head+AND+injury

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General recommendations on immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP) and the American Academy of Family Physicians (AAFP) Source: American Academy of Family Physicians - Medical Specialty Society; 2002 February 8; 36 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3180&nbr=2406&a mp;string=cerebral+AND+injuries

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Genetic counseling for fragile X syndrome: recommendations of the National Society of Genetic Counselors Source: National Society of Genetic Counselors; 2000; 23 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2546&nbr=1772&a mp;string=cerebral+AND+injuries

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Guideline for diagnostic laparoscopy Source: Society of American Gastrointestinal Endoscopic Surgeons - Medical Specialty Society; 1998 April; 4 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1861&nbr=1087&a mp;string=head+AND+injury

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Guideline for prevention of surgical site infection, 1999 Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 1999 April; 33 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1845&nbr=1071&a mp;string=head+AND+injury

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Guidelines for Alzheimer's disease management. Source: Alzheimer's Association of Los Angeles, Riverside and San Bernardino Counties - Private Nonprofit Organization; 1999 January 8 (revised 2002 Jan 1); 52 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3157&nbr=2383&a mp;string=cerebral+AND+injuries

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Guidelines for detection of thyroid dysfunction Source: American Thyroid Association - Professional Association; 2000 June 12; 3 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2361&nbr=1587&a mp;string=cerebral+AND+injuries

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Guidelines for emergency tracheal intubation immediately following traumatic injury Source: Eastern Association for the Surgery of Trauma - Professional Association; 2002; 80 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3222&nbr=2448&a mp;string=traumatic+AND+brain+AND+injury

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Guidelines for prehospital management of traumatic brain injury Source: Brain Trauma Foundation - Disease Specific Society; 2000; 81 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3288&nbr=2514&a mp;string=traumatic+AND+brain+AND+injury

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Guidelines for psychiatric and psychological evaluation of injured or chronically disabled workers Source: Washington State Department of Labor and Industries - State/Local Government Agency [U.S.]; 1999; 10 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1902&nbr=1128&a mp;string=head+AND+injury

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Guidelines for referral to pediatric surgical specialists Source: American Academy of Pediatrics - Medical Specialty Society; 2002 July; 5 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3420&nbr=2646&a mp;string=traumatic+AND+brain+AND+injury

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Guidelines for the diagnosis and management of blunt aortic injury Source: Eastern Association for the Surgery of Trauma - Professional Association; 2000; 20 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2676&nbr=1902&a mp;string=head+AND+injury

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Guidelines on management (diagnosis and treatment) of syncope Source: European Society of Cardiology - Medical Specialty Society; 2001 August; 51 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2974&nbr=2200&a mp;string=head+AND+injury

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Head injury in children Source: National Committee on Neuroscience (Singapore) - National Government Agency [Non-U.S.]; 2001 March; 38 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2834&nbr=2060&a mp;string=traumatic+AND+brain+AND+injury

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Health professional's guide to rehabilitation of the patient with osteoporosis Source: American Academy of Orthopaedic Surgeons - Medical Specialty Society; 2003; 31 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3863&nbr=3074&a mp;string=head+AND+injury

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Herniated disc. In: North American Spine Society phase III clinical guidelines for multidisciplinary spine care specialists Source: North American Spine Society - Medical Specialty Society; 2000; 104 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2803&nbr=2029&a mp;string=head+AND+injuries

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Hyperlipidemia medical nutrition therapy protocol Source: American Dietetic Association - Professional Association; 2001 June; Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3295&nbr=2521&a mp;string=cerebral+AND+injuries

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Hypertension diagnosis and treatment Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1995 June (revised 2003 Apr); 47 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3759&nbr=2985&a mp;string=cerebral+AND+injuries

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Identification, referral, and support of elders with genetic conditions Source: University of Iowa Gerontological Nursing Interventions Research Center, Research Dissemination Core - Academic Institution; 1999; 31 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1968&nbr=1194&a mp;string=cerebral+AND+injuries

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Indications for and techniques of red cell transfusion Source: Finnish Medical Society Duodecim - Professional Association; 2000 March 30; Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3402&nbr=2628&a mp;string=head+AND+injuries

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Inpatient management guidelines for people with diabetes Source: American Healthways, Inc - Public For Profit Organization; 1999 (revised 2002 Mar); 18 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3217&nbr=2443&a mp;string=cerebral+AND+injuries

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Intravenous immunoglobulin preparations Source: University HealthSystem Consortium - Private Nonprofit Organization; 1999 March; 216 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1976&nbr=1202&a mp;string=cerebral+AND+injuries

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K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification Source: National Kidney Foundation - Disease Specific Society; 2002 February; 246 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3192&nbr=2418&a mp;string=cerebral+AND+injuries

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Laboratory guidelines for screening, diagnosis, and monitoring of hepatic injury Source: American Association for the Study of Liver Diseases - Private Nonprofit Research Organization; 2000; 42 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3520&nbr=2746&a mp;string=traumatic+AND+brain+AND+injury

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Laboratory support for the diagnosis and monitoring of thyroid disease Source: National Academy of Clinical Biochemistry - Professional Association; 2002; 125 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3522&nbr=2748&a mp;string=head+AND+injuries

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Lipid management in adults Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1997 October (revised 2002 Jul); 61 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3410&nbr=2636&a mp;string=cerebral+AND+injuries

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Lung cancer. Palliative care Source: American College of Chest Physicians - Medical Specialty Society; 2003 January; 28 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3653&nbr=2879&a mp;string=traumatic+AND+brain+AND+injury

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Major depression in adults for mental health care providers Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1996 February (revised 2002 May); 43 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3354&nbr=2580&a mp;string=head+AND+injuries

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Management of acute myocardial infarction in patients presenting with ST-segment elevation Source: European Society of Cardiology - Medical Specialty Society; 1996 (revised 2003); 39 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3590&nbr=2816&a mp;string=head+AND+injury

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Management of breastfeeding for healthy full-term infants Source: Singapore Ministry of Health - National Government Agency [Non-U.S.]; 2002 December; 89 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3624&nbr=2850&a mp;string=traumatic+AND+brain+AND+injury

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Management of minor closed head injury in children Source: American Academy of Family Physicians - Medical Specialty Society; 1999 December; 16 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2272&nbr=1498&a mp;string=traumatic+AND+brain+AND+injury

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Management of patients with stroke. Rehabilitation, prevention and management of complications, and discharge planning. A national clinical guideline Source: Scottish Intercollegiate Guidelines Network - National Government Agency [Non-U.S.]; 1998 April (revised 2002 Nov); 48 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3538&nbr=2764&a mp;string=traumatic+AND+brain+AND+injury

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Management of sore throat and indications for tonsillectomy. A national clinical guideline Source: Scottish Intercollegiate Guidelines Network - National Government Agency [Non-U.S.]; 1999 January; 23 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1841&nbr=1067&a mp;string=head+AND+injury

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Management of type 2 diabetes mellitus Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1996 March (revised 2002 Sep); 77 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3499&nbr=2725&a mp;string=cerebral+AND+injuries

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Management of unerupted and impacted third molar teeth. A national clinical guideline Source: Scottish Intercollegiate Guidelines Network - National Government Agency [Non-U.S.]; 2000 March; 24 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2305&nbr=1531&a mp;string=head+AND+injury

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Mealtime difficulties for older persons: assessment and management Source: The John A. Hartford Foundation Institute for Geriatric Nursing - Academic Institution; 2003; 23 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3506&nbr=2732&a mp;string=head+AND+injury

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Migraine headache Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1998 November (revised 2002 Jul); 74 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3441&nbr=2667&a mp;string=head+AND+injuries

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Multiple myeloma (MM) Source: Finnish Medical Society Duodecim - Professional Association; 2001 December 27; Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3394&nbr=2620&a mp;string=head+AND+injury

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Neurologic complications in HIV-infected children and adolescents Source: New York State Department of Health - State/Local Government Agency [U.S.]; 2003 March; 19 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3821&nbr=3047&a mp;string=cerebral+AND+injuries

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Oral health management of children and adolescents with HIV infections Source: New York State Department of Health - State/Local Government Agency [U.S.]; 2003; 10 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3809&nbr=3035&a mp;string=head+AND+injuries

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Oral hygiene care for functionally dependent and cognitively impaired older adults Source: University of Iowa Gerontological Nursing Interventions Research Center, Research Dissemination Core - Academic Institution; 2002 November; 48 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3611&nbr=2837&a mp;string=traumatic+AND+brain+AND+injury

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Ottawa Ankle Rules for ankle injury radiography Source: Ottawa Health Research Institute - Hospital/Medical Center; 1999; Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=2807&nbr=2033&a mp;string=head+AND+injury

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Ottawa Knee Rule for knee injury radiography Source: Ottawa Health Research Institute - Hospital/Medical Center; 1999; Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=2808&nbr=2034&a mp;string=head+AND+injury

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Part II. Early indicators of prognosis in severe traumatic brain injury. In: Management and prognosis of severe traumatic brain injury Source: American Association of Neurological Surgeons - Medical Specialty Society; 2000; 116 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3122&nbr=2348&a mp;string=traumatic+AND+brain+AND+injury

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Pediatric eye and vision examination Source: American Optometric Association - Professional Association; 1994 (revised 2002); 57 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3548&nbr=2774&a mp;string=head+AND+injuries

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Pharmacologic management of acute attacks of migraine and prevention of migraine headache Source: American Academy of Family Physicians - Medical Specialty Society; 2002 November; 10 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3592&nbr=2818&a mp;string=cerebral+AND+injuries

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Physical activity in the prevention, treatment and rehabilitation of diseases Source: Finnish Medical Society Duodecim - Professional Association; 2002 May 7; Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3398&nbr=2624&a mp;string=cerebral+AND+injury

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Potassium iodide as a thyroid blocking agent in radiation emergencies Source: Food and Drug Administration (U.S.) - Federal Government Agency [U.S.]; 2001 November; 12 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3089&nbr=2315&a mp;string=head+AND+injury

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Practice guideline for psychiatric evaluation of adults. Source: American Psychiatric Association - Medical Specialty Society; 1995 (reviewed 2000); 28 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1407&nbr=665&am p;string=cerebral+AND+injuries

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Practice guidelines for the diagnosis and management of group A streptococcal pharyngitis Source: Infectious Diseases Society of America - Medical Specialty Society; 1997 (revised 2002 Jul); 13 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3349&nbr=2575&a mp;string=head+AND+injuries

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Practice management guidelines for geriatric trauma. Source: Eastern Association for the Surgery of Trauma - Professional Association; 2001; 55 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2959&nbr=2185&a mp;string=cerebral+AND+injuries

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Practice management guidelines for nutritional support of the trauma patient Source: Eastern Association for the Surgery of Trauma - Professional Association; 2001; 112 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2961&nbr=2187&a mp;string=head+AND+injury

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Practice management guidelines for the management of mild traumatic brain injury Source: Eastern Association for the Surgery of Trauma - Professional Association; 2000; 29 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2793&nbr=2019&a mp;string=traumatic+AND+brain+AND+injury

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Practice management guidelines for the management of venous thromboembolism in trauma patients Source: Eastern Association for the Surgery of Trauma - Professional Association; 1998 (revised 2001); 63 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3189&nbr=2415&a mp;string=head+AND+injury

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Practice management guidelines for the optimal timing of long bone fracture stabilization in polytrauma patients Source: Eastern Association for the Surgery of Trauma - Professional Association; 2000; 39 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2795&nbr=2021&a mp;string=traumatic+AND+brain+AND+injury

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Practice parameter for the prevention and management of aggressive behavior in child and adolescent psychiatric institutions with special reference to seclusion and restraint Source: American Academy of Child and Adolescent Psychiatry - Medical Specialty Society; 2001 May 13; 81 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3020&nbr=2246&a mp;string=head+AND+injuries

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Practice parameter for the use of stimulant medications in the treatment of children, adolescents, and adults Source: American Academy of Child and Adolescent Psychiatry - Medical Specialty Society; 2001 June 4; 96 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3018&nbr=2244&a mp;string=traumatic+AND+brain+AND+injury

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Practice parameter: diagnosis of dementia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology Source: American Academy of Neurology - Medical Specialty Society; 2001 May; 11 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2817&nbr=2043&a mp;string=cerebral+AND+injuries

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Practice parameter: early detection of dementia: mild cognitive impairment (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology Source: American Academy of Neurology - Medical Specialty Society; 2001 May; 10 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2816&nbr=2042&a mp;string=cerebral+AND+injuries

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Practice parameter: evaluation of the child with global developmental delay: report of the Quality Standards Subcommittee of the American Academy of Neurology and The Practice Committee of the Child Neurology Society Source: American Academy of Neurology - Medical Specialty Society; 2003 February 11; 14 pages http://www.guideline.gov/summary/summary.aspx?doc_id=4106&nbr=3151&a mp;string=cerebral+AND+injuries

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Practice parameter: evidence-based guidelines for migraine headache (an evidencebased review). Report of the Quality Standards Subcommittee of the American Academy of Neurology Source: American Academy of Neurology - Medical Specialty Society; 2000 September; 10 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2820&nbr=2046&a mp;string=cerebral+AND+injuries

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Practice parameter: management of dementia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology Source: American Academy of Neurology - Medical Specialty Society; 2001 May; 13 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2818&nbr=2044&a mp;string=cerebral+AND+injuries

•

Practice parameter: neuroimaging of the neonate: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society Source: American Academy of Neurology - Medical Specialty Society; 2002 June 25; 13 pages http://www.guideline.gov/summary/summary.aspx?doc_id=4100&nbr=3145&a mp;string=traumatic+AND+brain+AND+injury

•

Practice parameter: Screening and diagnosis of autism. Report of the Quality Standards Subcommittee of the American Academy of Neurology and the Child Neurology Society Source: American Academy of Neurology - Medical Specialty Society; 2000 August; 12 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2822&nbr=2048&a mp;string=head+AND+injury

•

Practice parameters for the assessment and treatment of children, adolescents, and adults with autism and other pervasive developmental disorders Source: American Academy of Child and Adolescent Psychiatry - Medical Specialty Society; 1999 June 27; 69 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2141&nbr=1367&a mp;string=head+AND+injury

•

Practice parameters for the assessment and treatment of children, adolescents, and adults with mental retardation and comorbid mental disorders Source: American Academy of Child and Adolescent Psychiatry - Medical Specialty Society; 1999 June 27; 77 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2140&nbr=1366&a mp;string=cerebral+AND+injuries

•

Practice parameters for the use of light therapy in the treatment of sleep disorders Source: American Academy of Sleep Medicine - Professional Association; 1999; 20 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2273&nbr=1499&a mp;string=cerebral+AND+injuries

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Practice parameters for using polysomnography to evaluate insomnia: an update Source: American Academy of Sleep Medicine - Professional Association; 1995 (revised 2003 Sep); 7 pages http://www.guideline.gov/summary/summary.aspx?doc_id=4370&nbr=3292&a mp;string=cerebral+AND+injuries

•

Pressure ulcer prevention and treatment following spinal cord injury Source: Consortium for Spinal Cord Medicine - Private Nonprofit Organization; 2000 August; 80 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2589&nbr=1815&a mp;string=head+AND+injury

•

Pressure ulcer risk assessment and prevention Source: Royal College of Nursing - Professional Association; 2001 April; 36 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2953&nbr=2179&a mp;string=head+AND+injury

•

Pressure ulcers Source: American Medical Directors Association - Professional Association; 1996 (reviewed January 2001, 2002, and 2003); 20 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1811&nbr=1037&a mp;string=head+AND+injury

•

Pressure ulcers in adults: prediction and prevention Source: Agency for Healthcare Research and Quality - Federal Government Agency [U.S.]; 1992 (reviewed 2000); 63 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2601&nbr=1827&a mp;string=head+AND+injury

•

Preventing falls in acute care Source: The John A. Hartford Foundation Institute for Geriatric Nursing - Academic Institution; 2003; 32 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3510&nbr=2736&a mp;string=traumatic+AND+brain+AND+injury

•

Preventing pressure ulcers and skin tears Source: The John A. Hartford Foundation Institute for Geriatric Nursing - Academic Institution; 2003; 37 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3511&nbr=2737&a mp;string=head+AND+injury

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Prevention of constipation in the older adult population Source: Registered Nurses Association of Ontario - Professional Association; 2002 January; 38 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3710&nbr=2936&a mp;string=cerebral+AND+injuries

•

Prevention of fall injuries in the older adult Source: Registered Nurses Association of Ontario - Professional Association; 2002 January; 57 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3712&nbr=2938&a mp;string=head+AND+injury

•

Prevention of pressure ulcers Source: University of Iowa Gerontological Nursing Interventions Research Center, Research Dissemination Core - Academic Institution; 1997 (revised 2002 May); 21 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3458&nbr=2684&a mp;string=head+AND+injury

•

Preventive counseling and education Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1995 May (revised 2003 Jul); 69 pages http://www.guideline.gov/summary/summary.aspx?doc_id=4177&nbr=3202&a mp;string=head+AND+injury

•

Preventive health care, 1999 update: 2. Echocardiography for the detection of a cardiac source of embolus in patients with stroke Source: Canadian Task Force on Preventive Health Care - National Government Agency [Non-U.S.]; 1999; 8 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2705&nbr=1931&a mp;string=cerebral+AND+injuries

•

Preventive health care, 2000 update. Use of ambulatory electrocardiography for the detection of paroxysmal atrial fibrillation in patients with stroke Source: Canadian Task Force on Preventive Health Care - National Government Agency [Non-U.S.]; 2000; 7 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2703&nbr=1929&a mp;string=cerebral+AND+injuries

268

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Preventive services for children and adolescents Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1995 June (revised 2003 Sep); 32 pages http://www.guideline.gov/summary/summary.aspx?doc_id=4178&nbr=3203&a mp;string=head+AND+injury

•

Procedure guideline for brain perfusion single photon computed tomography (SPECT) using Tc-99m radiopharmaceuticals Source: Society of Nuclear Medicine, Inc - Medical Specialty Society; 1999 February; 22 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1334&nbr=602&am p;string=traumatic+AND+brain+AND+injury

•

Procedure guideline for extended scintigraphy for differentiated thyroid cancer Source: Society of Nuclear Medicine, Inc - Medical Specialty Society; 1999 February; 15 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1363&nbr=621&am p;string=head+AND+injuries

•

Procedure guideline infection/inflammation

for

In-111

leukocyte

scintigraphy

for

suspected

Source: Society of Nuclear Medicine, Inc - Medical Specialty Society; 1999 February; 21 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1350&nbr=608&am p;string=skull+AND+fractures •

Procedure guideline for thyroid scintigraphy Source: Society of Nuclear Medicine, Inc - Medical Specialty Society; 1999 February; 15 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1364&nbr=622&am p;string=head+AND+injuries

•

Promoting continence using prompted voiding Source: Registered Nurses Association of Ontario - Professional Association; 2002 January; 40 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3711&nbr=2937&a mp;string=cerebral+AND+injuries

Patient Resources

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Public health guidance for community-level preparedness and response to severe acute respiratory syndrome (SARS). Version 2. Supplement I: infection control in healthcare, home, and community settings Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 2003 November 3 (revised 2004 January 8); 28 pages http://www.guideline.gov/summary/summary.aspx?doc_id=4593&nbr=3383&a mp;string=head+AND+injuries

•

Pulmonary rehabilitation Source: American Association for Respiratory Care - Professional Association; 2002; 9 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3211&nbr=2437&a mp;string=cerebral+AND+injuries

•

Recommendations for the treatment of pediculosis capitis (head lice) in children Source: University of Texas at Austin School of Nursing, Family Nurse Practitioner Program - Academic Institution; 2002 May; 13 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3225&nbr=2451&a mp;string=head+AND+injuries

•

Recommendations on selected interventions to prevent dental caries, oral and pharyngeal cancers, and sports-related craniofacial injuries Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 2002 July; 5 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3287&nbr=2513&a mp;string=traumatic+AND+brain+AND+injury

•

Recommendations to reduce injuries to motor vehicle occupants: increasing child safety seat use, increasing safety belt use, and reducing alcohol-impaired driving Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 2001 November; 7 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2841&nbr=2067&a mp;string=head+AND+injury

•

Rhinitis Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1998 August (revised 2003 May); 34 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3875&nbr=3084&a mp;string=head+AND+injuries

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Risk assessment and prevention of pressure ulcers Source: Registered Nurses Association of Ontario - Professional Association; 2002 January; 56 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3713&nbr=2939&a mp;string=head+AND+injury

•

Role of progestogen in hormone therapy for postmenopausal women: position statement of The North American Menopause Society Source: The North American Menopause Society - Private Nonprofit Organization; 2003 Mar-April; 20 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3736&nbr=2962&a mp;string=head+AND+injury

•

Screening for cognitive impairment and dementia in the elderly Source: Canadian Task Force on Preventive Health Care - National Government Agency [Non-U.S.]; 1994 January (revised 2001); 10 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2809&nbr=2035&a mp;string=cerebral+AND+injuries

•

Screening for dementia: recommendations and rationale Source: United States Preventive Services Task Force - Independent Expert Panel; 1996 (revised 2003 Jun); 12 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3690&nbr=2916&a mp;string=cerebral+AND+injuries

•

Screening for high blood pressure: recommendations and rationale Source: United States Preventive Services Task Force - Independent Expert Panel; 1996 (revised 2003 July 14); 12 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3853&nbr=3068&a mp;string=cerebral+AND+injuries

•

Screening for obesity in adults: recommendations and rationale Source: United States Preventive Services Task Force - Independent Expert Panel; 1996 (revised 2003 December 2); 13 pages http://www.guideline.gov/summary/summary.aspx?doc_id=4118&nbr=3163&a mp;string=cerebral+AND+injuries

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Secondary prevention of coronary heart disease following myocardial infarction. A national clinical guideline Source: Scottish Intercollegiate Guidelines Network - National Government Agency [Non-U.S.]; 2000 January; 26 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2303&nbr=1529&a mp;string=cerebral+AND+injuries

•

Selecting and using the most appropriate car safety seats for growing children: guidelines for counseling parents Source: American Academy of Pediatrics - Medical Specialty Society; 1996 May (revised 2002 Mar); 4 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3182&nbr=2408&a mp;string=head+AND+injury

•

Selection of an oxygen delivery device for neonatal and pediatric patients: 2002 revision and update Source: American Association for Respiratory Care - Professional Association; 1996 July (revised 2002 Jun); 10 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3249&nbr=2475&a mp;string=skull+AND+fracture

•

Shoulder Source: Work Loss Data Institute - Public For Profit Organization; 2003; 15 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3805&nbr=3032&a mp;string=head+AND+injury Healthfinder™

Healthfinder™ is sponsored by the U.S. Department of Health and Human Services and offers links to hundreds of other sites that contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database: •

Traumatic Brain Injury Source: National Dissemination Center for Children with Disabilities http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=3418

•

Traumatic Brain Injury (TBI)-Effects and Intervention Summary: healthfinder® — your guide to reliable health information health library just for you health care organizations search: go help | about healthfinder® Traumatic Brain Source: American Occupational Therapy Association http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7342

272

•


Traumatic Brain Injury Information Page Summary: A general overview of traumatic brain injury that includes a description of the disorder, treatment, prognosis and research information. Source: National Institute of Neurological Disorders and Stroke, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=3042

•

Traumatic Brain Injury: Hope Through Research Summary: Traumatic brain injury (TBI) is a major public health problem, especially among male adolescents and young adults ages 15 to 24, and among elderly people of both sexes 75 years and older. Source: National Institute of Neurological Disorders and Stroke, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7201 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 traumatic brain injury. 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

Patient Resources

273

Associations and Traumatic Brain Injury The following is a list of associations that provide information on and resources relating to traumatic brain injury: •

National Head Injury Foundation, Inc. (and Family Helpline) Telephone: (202) 296-6443 Toll-free: (800) 444-6443 Fax: (202) 296-8850 Email: [email protected] Web Site: http://www.biausa.org Background: Established in 1980, the National Head Injury Foundation, Inc. (NHIF) is a voluntary not-for-profit organization dedicated to promoting advocacy for people who have survived traumatic brain injury (TBI); securing and developing community based services for survivors of TBI and their families; supporting research that will enhance the lives of affected people; and promoting the prevention of brain injuries through public awareness, education, and legislation. The National Head Injury Foundation has a nationwide network of more than 800 support groups; provides direct financial assistance to people with a brain injury and their families; hosts nationwide conferences and symposia for physicians, rehabilitation specialists, trial lawyers, pharmaceutical representatives, and other professionals; and promotes a multifaceted public awareness campaign. The Foundation also spearheads a network of information exchange through its toll-free Family Helpline; Defense and Veterans Head Injury Program; advisory groups (e.g., the Survivor and Family Councils); and the Brain Injury Resource Center, an interactive computer-based multimedia system. The Foundation also offers a national directory of head injury services; a quarterly magazine, 'TBI Challenge!'; regular newsletters; and an extensive library that includes TBI research indexes, TBI professional series, books, videos, audiotapes, brochures, information packets, training materials, article reprints, and posters. Relevant area(s) of interest: Head Injury

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to traumatic brain injury. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with traumatic brain injury. 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 traumatic brain injury. 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.

274


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 “traumatic brain injury” (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 “traumatic brain injury”. Type the following hyperlink into your Web browser: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Then, select your preferred language and the format option “Organization Resource Sheet.” Type “traumatic brain injury” (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 “traumatic brain injury” (or a synonym) into the search box, and click “Submit Query.”

275

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.22

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

22

Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.

276


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)23: •

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/

23

Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.

Finding Medical Libraries

277

•

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/

278


•

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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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

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

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

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

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

Basic Guidelines for Traumatic Brain Injury Head injury Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000028.htm Skull fracture Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000060.htm

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Signs & Symptoms for Traumatic Brain Injury Altered level of consciousness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003202.htm Blurry Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003029.htm Cessation of breathing Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003069.htm

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Comatose Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003202.htm Confusion Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003205.htm Convulsions Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003200.htm Discouraged Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003213.htm Drowsiness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003208.htm Drowsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003208.htm Headache Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003024.htm Lethargy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003088.htm Loss of consciousness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003202.htm Restlessness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003212.htm Slurred speech Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003204.htm Stiff neck Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003261.htm Swelling Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003103.htm Vomit Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003117.htm Vomiting Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003117.htm •

Diagnostics and Tests for Traumatic Brain Injury Heart rate Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003399.htm

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•

Background Topics for Traumatic Brain Injury Analgesics Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002123.htm Bleeding Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000045.htm Choking Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000047.htm Fracture Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000001.htm Head injuries Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000028.htm Neck injury Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000029.htm Safety Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001931.htm Spinal injury Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000029.htm Unconscious Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000022.htm Wound Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000043.htm

Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •

Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical

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MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html

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Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/

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Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine

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TRAUMATIC BRAIN INJURY DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 1-Propanol: A colorless liquid made by oxidation of aliphatic hydrocarbons that is used as a solvent and chemical intermediate. [NIH] Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acetylcysteine: The N-acetyl derivative of cysteine. It is used as a mucolytic agent to reduce the viscosity of mucous secretions. It has also been shown to have antiviral effects in patients with HIV due to inhibition of viral stimulation by reactive oxygen intermediates. [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] Action Potentials: The electric response of a nerve or muscle to its stimulation. [NIH] Activities of Daily Living: The performance of the basic activities of self care, such as dressing, ambulation, eating, etc., in rehabilitation. [NIH] Acute Disease: Disease having a short and relatively severe course. [NIH] Acute myelogenous leukemia: AML. A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myeloid leukemia or acute nonlymphocytic leukemia. [NIH] Acute myeloid leukemia: AML. A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myelogenous leukemia or acute nonlymphocytic leukemia. [NIH] Acute nonlymphocytic leukemia: A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myeloid leukemia or acute myelogenous leukemia. [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

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enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adhesives: Substances that cause the adherence of two surfaces. They include glues (properly collagen-derived adhesives), mucilages, sticky pastes, gums, resins, or latex. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenal Glands: Paired glands situated in the retroperitoneal tissues at the superior pole of each kidney. [NIH] Adrenal insufficiency: The reduced secretion of adrenal glands. [NIH] Adrenal Medulla: The inner part of the adrenal gland; it synthesizes, stores and releases catecholamines. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Aerobic Metabolism: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as aerobic respiration, oxidative metabolism, or cell respiration. [NIH] Aerobic Respiration: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as oxidative metabolism, cell respiration, or aerobic metabolism. [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]

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Age of Onset: The age or period of life at which a disease or the initial symptoms or manifestations of a disease appear in an individual. [NIH] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] 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] 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] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Allergic Rhinitis: Inflammation of the nasal mucous membrane associated with hay fever; fits may be provoked by substances in the working environment. [NIH] Allylamine: Possesses an unusual and selective cytotoxicity for vascular smooth muscle cells in dogs and rats. Useful for experiments dealing with arterial injury, myocardial fibrosis or cardiac decompensation. [NIH] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Alternative Splicing: A process whereby multiple protein isoforms are generated from a single gene. Alternative splicing involves the splicing together of nonconsecutive exons during the processing of some, but not all, transcripts of the gene. Thus a particular exon may be connected to any one of several alternative exons to form messenger RNA. The alternative forms produce proteins in which one part is common while the other part is different. [NIH] Aluminum: A metallic element that has the atomic number 13, atomic symbol Al, and atomic weight 26.98. [NIH] Alveolar Process: The thickest and spongiest part of the maxilla and mandible hollowed out

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into deep cavities for the teeth. [NIH] Amantadine: An antiviral that is used in the prophylactic or symptomatic treatment of Influenza A. It is also used as an antiparkinsonian agent, to treat extrapyramidal reactions, and for postherpetic neuralgia. The mechanisms of its effects in movement disorders are not well understood but probably reflect an increase in synthesis and release of dopamine, with perhaps some inhibition of dopamine uptake. [NIH] Amenorrhea: Absence of menstruation. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Amnesia: Lack or loss of memory; inability to remember past experiences. [EU] Amnestic: Nominal aphasia; a difficulty in finding the right name for an object. [NIH] Amphetamine: A powerful central nervous system stimulant and sympathomimetic. Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. Amphetamine is also a drug of abuse and a psychotomimetic. The l- and the d,l-forms are included here. The l-form has less central nervous system activity but stronger cardiovascular effects. The d-form is dextroamphetamine. [NIH] Amputation: Surgery to remove part or all of a limb or appendage. [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] Amyloid beta-Protein: A 4 kD protein, 39-43 amino acids long, expressed by a gene located on chromosome 21. It is the major protein subunit of the vascular and plaque amyloid filaments in individuals with Alzheimer's disease and in aged individuals with trisomy 21 (Down syndrome). The protein is found predominantly in the nervous system, but there have been reports of its presence in non-neural tissue. [NIH] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of

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pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analgesics: Compounds capable of relieving pain without the loss of consciousness or without producing anesthesia. [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] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Anesthetics: Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. [NIH] 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] Angina: Chest pain that originates in the heart. [NIH] Angina Pectoris: The symptom of paroxysmal pain consequent to myocardial ischemia usually of distinctive character, location and radiation, and provoked by a transient stressful situation during which the oxygen requirements of the myocardium exceed the capacity of the coronary circulation to supply it. [NIH] 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] 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] Ankle: That part of the lower limb directly above the foot. [NIH] Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [NIH] Anovulation: Suspension or cessation of ovulation in animals and humans. [NIH] Anoxia: Clinical manifestation of respiratory distress consisting of a relatively complete absence of oxygen. [NIH] Anterior Cerebral Artery: Artery formed by the bifurcation of the internal carotid artery.

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Branches of the anterior cerebral artery supply the caudate nucleus, internal capsule, putamen, septal nuclei, gyrus cinguli, and surfaces of the frontal lobe and parietal lobe. [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] Anticonvulsants: Drugs used to prevent seizures or reduce their severity. [NIH] Antidepressant: A drug used to treat depression. [NIH] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Anti-infective: An agent that so acts. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [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] Antipsychotic: Effective in the treatment of psychosis. Antipsychotic drugs (called also neuroleptic drugs and major tranquilizers) are a chemically diverse (including phenothiazines, thioxanthenes, butyrophenones, dibenzoxazepines, dibenzodiazepines, and diphenylbutylpiperidines) but pharmacologically similar class of drugs used to treat schizophrenic, paranoid, schizoaffective, and other psychotic disorders; acute delirium and dementia, and manic episodes (during induction of lithium therapy); to control the movement disorders associated with Huntington's chorea, Gilles de la Tourette's syndrome, and ballismus; and to treat intractable hiccups and severe nausea and vomiting. Antipsychotic agents bind to dopamine, histamine, muscarinic cholinergic, a-adrenergic, and serotonin receptors. Blockade of dopaminergic transmission in various areas is thought to be responsible for their major effects : antipsychotic action by blockade in the mesolimbic and mesocortical areas; extrapyramidal side effects (dystonia, akathisia, parkinsonism, and tardive dyskinesia) by blockade in the basal ganglia; and antiemetic effects by blockade in the chemoreceptor trigger zone of the medulla. Sedation and autonomic side effects (orthostatic hypotension, blurred vision, dry mouth, nasal congestion and constipation) are caused by blockade of histamine, cholinergic, and adrenergic receptors. [EU]

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Antispasmodic: An agent that relieves spasm. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Anxiety Disorders: Disorders in which anxiety (persistent feelings of apprehension, tension, or uneasiness) is the predominant disturbance. [NIH] Anxiolytic: An anxiolytic or antianxiety agent. [EU] Aorta: The main trunk of the systemic arteries. [NIH] Apathy: Lack of feeling or emotion; indifference. [EU] Aperture: A natural hole of perforation, especially one in a bone. [NIH] Aphasia: A cognitive disorder marked by an impaired ability to comprehend or express language in its written or spoken form. This condition is caused by diseases which affect the language areas of the dominant hemisphere. Clinical features are used to classify the various subtypes of this condition. General categories include receptive, expressive, and mixed forms of aphasia. [NIH] Apnea: A transient absence of spontaneous respiration. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Applicability: A list of the commodities to which the candidate method can be applied as presented or with minor modifications. [NIH] Apraxia: Loss of ability to perform purposeful movements, in the absence of paralysis or sensory disturbance, caused by lesions in the cortex. [NIH] Aqueous: Having to do with water. [NIH] Arachidonate 12-Lipoxygenase: An enzyme that catalyzes the oxidation of arachidonic acid to yield 12-hydroperoxyarachidonate (12-HPETE) which is itself rapidly converted by a peroxidase to 12-hydroxy-5,8,10,14-eicosatetraenoate (12-HETE). The 12-hydroperoxides are preferentially formed in platelets. EC 1.13.11.31. [NIH] Arachidonate 15-Lipoxygenase: An enzyme that catalyzes the oxidation of arachidonic acid to yield 15-hydroperoxyarachidonate (15-HPETE) which is rapidly converted to 15-hydroxy5,8,11,13-eicosatetraenoate (15-HETE). The 15-hydroperoxides are preferentially formed in neutrophils and lymphocytes. EC 1.13.11.33. [NIH] Arachidonate Lipoxygenases: Enzymes catalyzing the oxidation of arachidonic acid to hydroperoxyarachidonates (HPETES). These products are then rapidly converted by a peroxidase to hydroxyeicosatetraenoic acids (HETES). The positional specificity of the enzyme reaction varies from tissue to tissue. The final lipoxygenase pathway leads to the leukotrienes. EC 1.13.11.- . [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]

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Arrhythmia: Any variation from the normal rhythm or rate of the heart beat. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteriovenous: Both arterial and venous; pertaining to or affecting an artery and a vein. [EU] Articular: Of or pertaining to a joint. [EU] Articulation: The relationship of two bodies by means of a moveable joint. [NIH] Aspartate: A synthetic amino acid. [NIH] Aspartic: The naturally occurring substance is L-aspartic acid. One of the acidic-amino-acids is obtained by the hydrolysis of proteins. [NIH] Aspartic Acid: One of the non-essential amino acids commonly occurring in the L-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a neurotransmitter. [NIH] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] Asymptomatic: Having no signs or symptoms of disease. [NIH] Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharnyx, larnyx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. [NIH] Atopic: Pertaining to an atopen or to atopy; allergic. [EU] Atrial: Pertaining to an atrium. [EU] Atrial Fibrillation: Disorder of cardiac rhythm characterized by rapid, irregular atrial impulses and ineffective atrial contractions. [NIH] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Atropine: A toxic alkaloid, originally from Atropa belladonna, but found in other plants, mainly Solanaceae. [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]

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Audition: The sense of hearing. [NIH] Auditory: Pertaining to the sense of hearing. [EU] Autodigestion: Autolysis; a condition found in disease of the stomach: the stomach wall is digested by the gastric juice. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by autoimmune diseases. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Autonomic Nervous System: The enteric, parasympathetic, and sympathetic nervous systems taken together. Generally speaking, the autonomic nervous system regulates the internal environment during both peaceful activity and physical or emotional stress. Autonomic activity is controlled and integrated by the central nervous system, especially the hypothalamus and the solitary nucleus, which receive information relayed from visceral afferents; these and related central and sensory structures are sometimes (but not here) considered to be part of the autonomic nervous system itself. [NIH] Autopsy: Postmortem examination of the body. [NIH] Autoradiography: A process in which radioactive material within an object produces an image when it is in close proximity to a radiation sensitive emulsion. [NIH] 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] Bacillus: A genus of Bacillaceae that are spore-forming, rod-shaped cells. Most species are saprophytic soil forms with only a few species being pathogenic. [NIH] Back Pain: Acute or chronic pain located in the posterior regions of the trunk, including the thoracic, lumbar, sacral, or adjacent regions. [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] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Barbiturates: A class of chemicals derived from barbituric acid or thiobarbituric acid. Many of these are medically important as sedatives and hypnotics (sedatives, barbiturate), as anesthetics, or as anticonvulsants. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] 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]

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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] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] Basophil: A type of white blood cell. Basophils are granulocytes. [NIH] Bed Rest: Confinement of an individual to bed for therapeutic or experimental reasons. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Benign prostatic hyperplasia: A benign (noncancerous) condition in which an overgrowth of prostate tissue pushes against the urethra and the bladder, blocking the flow of urine. Also called benign prostatic hypertrophy or BPH. [NIH] Beta-pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Bewilderment: Impairment or loss of will power. [NIH] Bifida: A defect in development of the vertebral column in which there is a central deficiency of the vertebral lamina. [NIH] Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Biliary Tract: The gallbladder and its ducts. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biological Transport: The movement of materials (including biochemical substances and drugs) across cell membranes and epithelial layers, usually by passive diffusion. [NIH] Biomechanics: The study of the application of mechanical laws and the action of forces to living structures. [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

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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] Biphasic: Having two phases; having both a sporophytic and a gametophytic phase in the life cycle. [EU] Bipolar Disorder: A major affective disorder marked by severe mood swings (manic or major depressive episodes) and a tendency to remission and recurrence. [NIH] Bladder: The organ that stores urine. [NIH] Blast phase: The phase of chronic myelogenous leukemia in which the number of immature, abnormal white blood cells in the bone marrow and blood is extremely high. Also called blast crisis. [NIH] Bloating: Fullness or swelling in the abdomen that often occurs after meals. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood transfusion: The administration of blood or blood products into a blood vessel. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blood Viscosity: The internal resistance of the blood to shear forces. The in vitro measure of whole blood viscosity is of limited clinical utility because it bears little relationship to the actual viscosity within the circulation, but an increase in the viscosity of circulating blood can contribute to morbidity in patients suffering from disorders such as sickle cell anemia and polycythemia. [NIH] 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 Fluids: Liquid components of living organisms. [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

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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 metastases: Cancer that has spread from the original (primary) tumor to the bone. [NIH]

Bone Resorption: Bone loss due to osteoclastic activity. [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] Boron: A trace element with the atomic symbol B, atomic number 5, and atomic weight 10.81. Boron-10, an isotope of boron, is used as a neutron absorber in boron neutron capture therapy. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Brain Diseases: Pathologic conditions affecting the brain, which is composed of the intracranial components of the central nervous system. This includes (but is not limited to) the cerebral cortex; intracranial white matter; basal ganglia; thalamus; hypothalamus; brain stem; and cerebellum. [NIH] Brain Hypoxia: Lack of oxygen leading to unconsciousness. [NIH] Brain Infarction: The formation of an area of necrosis in the brain, including the cerebral hemispheres (cerebral infarction), thalami, basal ganglia, brain stem (brain stem infarctions), or cerebellum secondary to an insufficiency of arterial or venous blood flow. [NIH] Brain Injuries: Acute and chronic injuries to the brain, including the cerebral hemispheres, cerebellum, and brain stem. Clinical manifestations depend on the nature of injury. Diffuse trauma to the brain is frequently associated with diffuse axonal injury or coma, posttraumatic. Localized injuries may be associated with neurobehavioral manifestations; hemiparesis, or other focal neurologic deficits. [NIH] Brain Ischemia: Localized reduction of blood flow to brain tissue due to arterial obtruction or systemic hypoperfusion. This frequently occurs in conjuction with brain hypoxia. Prolonged ischemia is associated with brain infarction. [NIH] Brain Stem: The part of the brain that connects the cerebral hemispheres with the spinal cord. It consists of the mesencephalon, pons, and medulla oblongata. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Breakdown: A physical, metal, or nervous collapse. [NIH] Bromocriptine: A semisynthetic ergot alkaloid that is a dopamine D2 agonist. It suppresses prolactin secretion and is used to treat amenorrhea, galactorrhea, and female infertility, and has been proposed for Parkinson disease. [NIH] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH]

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Bronchial: Pertaining to one or more bronchi. [EU] Bronchial Hyperreactivity: Tendency of the smooth muscle of the tracheobronchial tree to contract more intensely in response to a given stimulus than it does in the response seen in normal individuals. This condition is present in virtually all symptomatic patients with asthma. The most prominent manifestation of this smooth muscle contraction is a decrease in airway caliber that can be readily measured in the pulmonary function laboratory. [NIH] Bronchitis: Inflammation (swelling and reddening) of the bronchi. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Bulbar: Pertaining to a bulb; pertaining to or involving the medulla oblongata, as bulbar paralysis. [EU] Bypass: A surgical procedure in which the doctor creates a new pathway for the flow of body fluids. [NIH] Cachexia: General ill health, malnutrition, and weight loss, usually associated with chronic disease. [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 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] Calmodulin: A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels. [NIH] 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] Cannabidiol: Compound isolated from Cannabis sativa extract. [NIH] Cannabinoids: Compounds extracted from Cannabis sativa L. and metabolites having the cannabinoid structure. The most active constituents are tetrahydrocannabinol, cannabinol, and cannabidiol. [NIH] Cannabinol: A physiologically inactive constituent of Cannabis sativa L. [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]

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Carbon Monoxide Poisoning: Toxic asphyxiation due to the displacement of oxygen from oxyhemoglobin by carbon monoxide. [NIH] Carboxy: Cannabinoid. [NIH] Carboxy-terminal: The end of any polypeptide or protein that bears a free carboxyl group. [NIH]

Carcinogenic: Producing carcinoma. [EU] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]

Cardiac: Having to do with the heart. [NIH] Cardiac arrest: A sudden stop of heart function. [NIH] 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] Cardiopulmonary: Having to do with the heart and lungs. [NIH] Cardiopulmonary Bypass: Diversion of the flow of blood from the entrance of the right atrium directly to the aorta (or femoral artery) via an oxygenator thus bypassing both the heart and lungs. [NIH] Cardiopulmonary Resuscitation: The artificial substitution of heart and lung action as indicated for heart arrest resulting from electric shock, drowning, respiratory arrest, or other causes. The two major components of cardiopulmonary resuscitation are artificial ventilation and closed-chest cardiac massage. [NIH] Cardiopulmonary Resuscitation: The artificial substitution of heart and lung action as indicated for heart arrest resulting from electric shock, drowning, respiratory arrest, or other causes. The two major components of cardiopulmonary resuscitation are artificial ventilation and closed-chest cardiac massage. [NIH] Cardiorespiratory: Relating to the heart and lungs and their function. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] 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] Carotene: The general name for a group of pigments found in green, yellow, and leafy vegetables, and yellow fruits. The pigments are fat-soluble, unsaturated aliphatic hydrocarbons functioning as provitamins and are converted to vitamin A through enzymatic processes in the intestinal wall. [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] Caspase: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] Cataract: An opacity, partial or complete, of one or both eyes, on or in the lens or capsule, especially an opacity impairing vision or causing blindness. The many kinds of cataract are

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classified by their morphology (size, shape, location) or etiology (cause and time of occurrence). [EU] 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] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Causal: Pertaining to a cause; directed against a cause. [EU] 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 Cycle: The complex series of phenomena, occurring between the end of one cell division and the end of the next, by which cellular material is divided between daughter cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] 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] Cellular metabolism: The sum of all chemical changes that take place in a cell through which energy and basic components are provided for essential processes, including the synthesis of new molecules and the breakdown and removal of others. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Central Nervous System Infections: Pathogenic infections of the brain, spinal cord, and meninges. DNA virus infections; RNA virus infections; bacterial infections; mycoplasma infections; Spirochaetales infections; fungal infections; protozoan infections; helminthiasis; and prion diseases may involve the central nervous system as a primary or secondary

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process. [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 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 Infarction: The formation of an area of necrosis in the cerebrum caused by an insufficiency of arterial or venous blood flow. Infarcts of the cerebrum are generally classified by hemisphere (i.e., left vs. right), lobe (e.g., frontal lobe infarction), arterial distribution (e.g., infarction, anterior cerebral artery), and etiology (e.g., embolic infarction). [NIH]

Cerebral Palsy: Refers to a motor disability caused by a brain dysfunction. [NIH] Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] Chelation: Combination with a metal in complexes in which the metal is part of a ring. [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 Pain: Pressure, burning, or numbness in the chest. [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] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Choline: A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism. [NIH] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing

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acetylcholine or a related compound. [EU] Cholinesterase Inhibitors: Drugs that inhibit cholinesterases. The neurotransmitter acetylcholine is rapidly hydrolyzed, and thereby inactivated, by cholinesterases. When cholinesterases are inhibited, the action of endogenously released acetylcholine at cholinergic synapses is potentiated. Cholinesterase inhibitors are widely used clinically for their potentiation of cholinergic inputs to the gastrointestinal tract and urinary bladder, the eye, and skeletal muscles; they are also used for their effects on the heart and the central nervous system. [NIH] Chorea: Involuntary, forcible, rapid, jerky movements that may be subtle or become confluent, markedly altering normal patterns of movement. Hypotonia and pendular reflexes are often associated. Conditions which feature recurrent or persistent episodes of chorea as a primary manifestation of disease are referred to as choreatic disorders. Chorea is also a frequent manifestation of basal ganglia diseases. [NIH] Choreatic Disorders: Acquired and hereditary conditions which feature chorea as a primary manifestation of the disease process. [NIH] Chromaffin Cells: Cells that store epinephrine secretory vesicles. During times of stress, the nervous system signals the vesicles to secrete their hormonal content. Their name derives from their ability to stain a brownish color with chromic salts. Characteristically, they are located in the adrenal medulla and paraganglia (paraganglia, chromaffin) of the sympathetic 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] Chromic: Catgut sterilized and impregnated with chromium trioxide. [NIH] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Chronic lymphocytic leukemia: A slowly progressing disease in which too many white blood cells (called lymphocytes) are found in the body. [NIH] Chronic myelogenous leukemia: CML. A slowly progressing disease in which too many white blood cells are made in the bone marrow. Also called chronic myeloid leukemia or chronic granulocytic leukemia. [NIH] Chronic Obstructive Pulmonary Disease: Collective term for chronic bronchitis and emphysema. [NIH] Chronic phase: Refers to the early stages of chronic myelogenous leukemia or chronic lymphocytic leukemia. The number of mature and immature abnormal white blood cells in the bone marrow and blood is higher than normal, but lower than in the accelerated or blast phase. [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] Circadian Rhythm: The regular recurrence, in cycles of about 24 hours, of biological processes or activities, such as sensitivity to drugs and stimuli, hormone secretion, sleeping, feeding, etc. This rhythm seems to be set by a 'biological clock' which seems to be set by recurring daylight and darkness. [NIH]

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Circulatory system: The system that contains the heart and the blood vessels and moves blood throughout the body. This system helps tissues get enough oxygen and nutrients, and it helps them get rid of waste products. The lymph system, which connects with the blood system, is often considered part of the circulatory system. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Clamp: A u-shaped steel rod used with a pin or wire for skeletal traction in the treatment of certain fractures. [NIH] Claudication: Limping or lameness. [EU] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]

Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] 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] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Cofactor: A substance, microorganism or environmental factor that activates or enhances the 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] Cognition Disorders: Disturbances in the mental process related to thinking, reasoning, and

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judgment. [NIH] Cognitive restructuring: A method of identifying and replacing fear-promoting, irrational beliefs with more realistic and functional ones. [NIH] Colitis: Inflammation of the colon. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collagen disease: A term previously used to describe chronic diseases of the connective tissue (e.g., rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis), but now is thought to be more appropriate for diseases associated with defects in collagen, which is a component of the connective tissue. [NIH] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Colloidal: Of the nature of a colloid. [EU] Comatose: Pertaining to or affected with coma. [EU] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [NIH] Communication Disorders: Disorders of verbal and nonverbal communication caused by receptive or expressive language disorders, cognitive dysfunction (e.g., mental retardation), psychiatric conditions, and hearing disorders. [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

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are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] 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] Cones: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide sharp central vision and color vision. [NIH] Confusion: A mental state characterized by bewilderment, emotional disturbance, lack of clear thinking, and perceptual disorientation. [NIH] 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] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Consolidation: The healing process of a bone fracture. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constitutional: 1. Affecting the whole constitution of the body; not local. 2. Pertaining to the constitution. [EU] Constriction: The act of constricting. [NIH]

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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] Consumption: Pulmonary tuberculosis. [NIH] Continence: The ability to hold in a bowel movement or urine. [NIH] Continuum: An area over which the vegetation or animal population is of constantly changing composition so that homogeneous, separate communities cannot be distinguished. [NIH]

Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Contralateral: Having to do with the opposite side of the body. [NIH] Controlled clinical trial: A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all. [NIH] Contusion: A bruise; an injury of a part without a break in the skin. [EU] 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] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Circulation: The circulation of blood through the coronary vessels of the heart. [NIH]

Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH]

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Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [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] Corticosteroids: Hormones that have antitumor activity in lymphomas and lymphoid leukemias; in addition, corticosteroids (steroids) may be used for hormone replacement and for the management of some of the complications of cancer and its treatment. [NIH] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] 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] Craniotomy: An operation in which an opening is made in the skull. [NIH] Creatine: An amino acid that occurs in vertebrate tissues and in urine. In muscle tissue, creatine generally occurs as phosphocreatine. Creatine is excreted as creatinine in the urine. [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] Critical Illness: A disease or state in which death is possible or imminent. [NIH] Cues: Signals for an action; that specific portion of a perceptual field or pattern of stimuli to which a subject has learned to respond. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Curcumin: A dye obtained from tumeric, the powdered root of Curcuma longa Linn. It is used in the preparation of curcuma paper and the detection of boron. Curcumin appears to possess a spectrum of pharmacological properties, due primarily to its inhibitory effects on metabolic enzymes. [NIH] Cutaneous: Having to do with the skin. [NIH] Cyanide: An extremely toxic class of compounds that can be lethal on inhaling of ingesting in minute quantities. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cycloserine: Antibiotic substance produced by Streptomyces garyphalus. It may be used in the treatment of resistant tuberculosis as part of a multi-drug regimen. It has also been used in urinary tract infections. [NIH] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cystine: A covalently linked dimeric nonessential amino acid formed by the oxidation of

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cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. [NIH]

Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . 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]

Cytotoxic: Cell-killing. [NIH] Data Collection: Systematic gathering of data for a particular purpose from various sources, including questionnaires, interviews, observation, existing records, and electronic devices. The process is usually preliminary to statistical analysis of the data. [NIH] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH] Decubitus: An act of lying down; also the position assumed in lying down. [EU] Decubitus Ulcer: An ulceration caused by prolonged pressure in patients permitted to lie too still for a long period of time. The bony prominences of the body are the most frequently affected sites. The ulcer is caused by ischemia of the underlying structures of the skin, fat, and muscles as a result of the sustained and constant pressure. [NIH] Defibrillation: The act to arrest the fibrillation of (heart muscle) by applying electric shock across the chest, thus depolarizing the heart cells and allowing normal rhythm to return. [EU] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Delirium: (DSM III-R) an acute, reversible organic mental disorder characterized by reduced ability to maintain attention to external stimuli and disorganized thinking as manifested by rambling, irrelevant, or incoherent speech; there are also a reduced level of consciousness, sensory misperceptions, disturbance of the sleep-wakefulness cycle and level of psychomotor activity, disorientation to time, place, or person, and memory impairment. Delirium may be caused by a large number of conditions resulting in derangement of

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cerebral metabolism, including systemic infection, poisoning, drug intoxication or withdrawal, seizures or head trauma, and metabolic disturbances such as hypoxia, hypoglycaemia, fluid, electrolyte, or acid-base imbalances, or hepatic or renal failure. Called also acute confusional state and acute brain syndrome. [EU] Delivery of Health Care: The concept concerned with all aspects of providing and distributing health services to a patient population. [NIH] Delusions: A false belief regarding the self or persons or objects outside the self that persists despite the facts, and is not considered tenable by one's associates. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Demyelinating Diseases: Diseases characterized by loss or dysfunction of myelin in the central or peripheral nervous system. [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] Dental Caries: Localized destruction of the tooth surface initiated by decalcification of the enamel followed by enzymatic lysis of organic structures and leading to cavity formation. If left unchecked, the cavity may penetrate the enamel and dentin and reach the pulp. The three most prominent theories used to explain the etiology of the disase are that acids produced by bacteria lead to decalcification; that micro-organisms destroy the enamel protein; or that keratolytic micro-organisms produce chelates that lead to decalcification. [NIH]

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] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Depressive Disorder: An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent. [NIH] Deprivation: Loss or absence of parts, organs, powers, or things that are needed. [EU] Dermatitis: Any inflammation of the skin. [NIH] Detergents: Purifying or cleansing agents, usually salts of long-chain aliphatic bases or acids, that exert cleansing (oil-dissolving) and antimicrobial effects through a surface action that depends on possessing both hydrophilic and hydrophobic properties. [NIH] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Dextroamphetamine: The d-form of amphetamine. It is a central nervous system stimulant

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and a sympathomimetic. It has also been used in the treatment of narcolepsy and of attention deficit disorders and hyperactivity in children. Dextroamphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulating release of monamines, and inhibiting monoamine oxidase. It is also a drug of abuse and a psychotomimetic. [NIH] 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 Imaging: Any visual display of structural or functional patterns of organs or tissues for diagnostic evaluation. It includes measuring physiologic and metabolic responses to physical and chemical stimuli, as well as ultramicroscopy. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diagnostic Services: Organized services for the purpose of providing diagnosis to promote and maintain health. [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] Diarrhoea: Abnormal frequency and liquidity of faecal discharges. [EU] Diastolic: Of or pertaining to the diastole. [EU] Diastolic blood pressure: The minimum pressure that remains within the artery when the heart is at rest. [NIH] Diencephalon: The paired caudal parts of the prosencephalon from which the thalamus, hypothalamus, epithalamus, and subthalamus are derived. [NIH] Diffuse Axonal Injury: A relatively common sequela of blunt head injury, characterized by a global disruption of axons throughout the brain. Associated clinical features may include neurobehavioral manifestations; persistent vegetative state; dementia; and other disorders. [NIH]

Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Dihydroxy: AMPA/Kainate antagonist. [NIH] Dilatation: The act of dilating. [NIH] Dilution: A diluted or attenuated medicine; in homeopathy, the diffusion of a given quantity of a medicinal agent in ten or one hundred times the same quantity of water. [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]

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Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] 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] 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] Diuretic: A drug that increases the production of urine. [NIH] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] Domestic Violence: Deliberate, often repetitive, physical abuse by one family member against another: marital partners, parents, children, siblings, or any other member of a household. [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] 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]

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Duodenum: The first part of the small intestine. [NIH] Dura mater: The outermost, toughest, and most fibrous of the three membranes (meninges) covering the brain and spinal cord; called also pachymeninx. [EU] 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] Dysarthria: Imperfect articulation of speech due to disturbances of muscular control which result from damage to the central or peripheral nervous system. [EU] Dyskinesias: Abnormal involuntary movements which primarily affect the extremities, trunk, or jaw that occur as a manifestation of an underlying disease process. Conditions which feature recurrent or persistent episodes of dyskinesia as a primary manifestation of disease may be referred to as dyskinesia syndromes (movement disorders). Dyskinesias are also a relatively common manifestation of basal ganglia diseases. [NIH] Dyslexia: Partial alexia in which letters but not words may be read, or in which words may be read but not understood. [NIH] Dysmenorrhea: Painful menstruation. [NIH] Dysphagia: Difficulty in swallowing. [EU] Dysphoric: A feeling of unpleasantness and discomfort. [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] Eicosanoids: A class of oxygenated, endogenous, unsaturated fatty acids derived from arachidonic acid. They include prostaglandins, leukotrienes, thromboxanes, and hydroxyeicosatetraenoic acid compounds (HETE). They are hormone-like substances that act near the site of synthesis without altering functions throughout the body. [NIH] Elastin: The protein that gives flexibility to tissues. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electric shock: A dangerous patho-physiological effect resulting from an electric current passing through the body of a human or animal. [NIH] Electrocardiography: Recording of the moment-to-moment electromotive forces of the heart as projected onto various sites on the body's surface, delineated as a scalar function of time. [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]

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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] Electroshock: Induction of a stress reaction in experimental subjects by means of an electrical shock; applies to either convulsive or non-convulsive states. [NIH] Elementary Particles: Individual components of atoms, usually subatomic; subnuclear particles are usually detected only when the atomic nucleus decays and then only transiently, as most of them are unstable, often yielding pure energy without substance, i.e., radiation. [NIH] Embolism: Blocking of a blood vessel by a blood clot or foreign matter that has been transported from a distant site by the blood stream. [NIH] 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] Embryology: The study of the development of an organism during the embryonic and fetal stages of life. [NIH] Emesis: Vomiting; an act of vomiting. Also used as a word termination, as in haematemesis. [EU]

Emetic: An agent that causes vomiting. [EU] Emphysema: A pathological accumulation of air in tissues or organs. [NIH] Empirical: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] Emulsion: A preparation of one liquid distributed in small globules throughout the body of a second liquid. The dispersed liquid is the discontinuous phase, and the dispersion medium is the continuous phase. When oil is the dispersed liquid and an aqueous solution is the continuous phase, it is known as an oil-in-water emulsion, whereas when water or aqueous solution is the dispersed phase and oil or oleaginous substance is the continuous phase, it is known as a water-in-oil emulsion. Pharmaceutical emulsions for which official standards have been promulgated include cod liver oil emulsion, cod liver oil emulsion with malt, liquid petrolatum emulsion, and phenolphthalein in liquid petrolatum emulsion. [EU] Enamel: A very hard whitish substance which covers the dentine of the anatomical crown of a tooth. [NIH] Encapsulated: Confined to a specific, localized area and surrounded by a thin layer of tissue. [NIH]

Encephalitis: Inflammation of the brain due to infection, autoimmune processes, toxins, and other conditions. Viral infections (see encephalitis, viral) are a relatively frequent cause of this condition. [NIH] Encephalitis, Viral: Inflammation of brain parenchymal tissue as a result of viral infection. Encephalitis may occur as primary or secondary manifestation of Togaviridae infections; Herpesviridae infections; Adenoviridae infections; Flaviviridae infections; Bunyaviridae

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infections; Picornaviridae infections; Paramyxoviridae infections; Orthomyxoviridae infections; Retroviridae infections; and Arenaviridae infections. [NIH] Encephalomyelitis: A general term indicating inflammation of the brain and spinal cord, often used to indicate an infectious process, but also applicable to a variety of autoimmune and toxic-metabolic conditions. There is significant overlap regarding the usage of this term and encephalitis in the literature. [NIH] Encephalopathy: A disorder of the brain that can be caused by disease, injury, drugs, or chemicals. [NIH] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endocrine System: The system of glands that release their secretions (hormones) directly into the circulatory system. In addition to the endocrine glands, included are the chromaffin system and the neurosecretory systems. [NIH] Endocrinology: A subspecialty of internal medicine concerned with the metabolism, physiology, and disorders of the endocrine system. [NIH] 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, Lymphatic: Unbroken cellular lining (intima) of the lymph vessels (e.g., the high endothelial lymphatic venules). It is more permeable than vascular endothelium, lacking selective absorption and functioning mainly to remove plasma proteins that have filtered through the capillaries into the tissue spaces. [NIH] Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components from interstitium to lumen; this function has been most intensively studied in the blood capillaries. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxic: Of, relating to, or acting as an endotoxin (= a heat-stable toxin, associated with the outer membranes of certain gram-negative bacteria. Endotoxins are not secreted and are released only when the cells are disrupted). [EU] Endotoxin: Toxin from cell walls of bacteria. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Enhancer: Transcriptional element in the virus genome. [NIH] Entorhinal Cortex: Cortex where the signals are combined with those from other sensory systems. [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] Eosinophil: A polymorphonuclear leucocyte with large eosinophilic granules in its cytoplasm, which plays a role in hypersensitivity reactions. [NIH]

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Eosinophilic: A condition found primarily in grinding workers caused by a reaction of the pulmonary tissue, in particular the eosinophilic cells, to dust that has entered the lung. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidemiological: Relating to, or involving epidemiology. [EU] Epidermoid carcinoma: A type of cancer in which the cells are flat and look like fish scales. Also called squamous cell carcinoma. [NIH] Epilepticus: Repeated and prolonged epileptic seizures without recovery of consciousness between attacks. [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Erection: The condition of being made rigid and elevated; as erectile tissue when filled with blood. [EU] Ergot: Cataract due to ergot poisoning caused by eating of rye cereals contaminated by a fungus. [NIH] ERV: The expiratory reserve volume is the largest volume of gas that can be expired from the end-expiratory level. [NIH] Erythema: Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of causes. [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] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Estrogen: One of the two female sex hormones. [NIH] Estrogen receptor: ER. Protein found on some cancer cells to which estrogen will attach. [NIH]

Estrogen Receptor Modulators: Substances that possess antiestrogenic actions but can also produce estrogenic effects as well. They act as complete or partial agonist or as antagonist. They can be either steroidal or nonsteroidal in structure. [NIH] Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Ethnic Groups: A group of people with a common cultural heritage that sets them apart from others in a variety of social relationships. [NIH]

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Evacuation: An emptying, as of the bowels. [EU] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Evoked Potentials: The electric response evoked in the central nervous system by stimulation of sensory receptors or some point on the sensory pathway leading from the receptor to the cortex. The evoked stimulus can be auditory, somatosensory, or visual, although other modalities have been reported. Event-related potentials is sometimes used synonymously with evoked potentials but is often associated with the execution of a motor, cognitive, or psychophysiological task, as well as with the response to a stimulus. [NIH] Excitability: Property of a cardiac cell whereby, when the cell is depolarized to a critical level (called threshold), the membrane becomes permeable and a regenerative inward current causes an action potential. [NIH] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] Excitatory Amino Acid Agonists: Drugs that bind to and activate excitatory amino acid receptors. [NIH] Excitatory Amino Acids: Endogenous amino acids released by neurons as excitatory neurotransmitters. Glutamic acid is the most common excitatory neurotransmitter in the brain. Aspartic acid has been regarded as an excitatory transmitter for many years, but the extent of its role as a transmitter is unclear. [NIH] Excitotoxicity: Excessive exposure to glutamate or related compounds can kill brain neurons, presumably by overstimulating them. [NIH] Exhaustion: The feeling of weariness of mind and body. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exon: The part of the DNA that encodes the information for the actual amino acid sequence of the protein. In many eucaryotic genes, the coding sequences consist of a series of exons alternating with intron sequences. [NIH] Expectorant: 1. Promoting the ejection, by spitting, of mucus or other fluids from the lungs and trachea. 2. An agent that promotes the ejection of mucus or exudate from the lungs, bronchi, and trachea; sometimes extended to all remedies that quiet cough (antitussives). [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] Extender: Any of several colloidal substances of high molecular weight, used as a blood or plasma substitute in transfusion for increasing the volume of the circulating blood. [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 Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture

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dishes adhere. [NIH] Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., collagen, elastin, fibronectins and laminin). [NIH] 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] Extrapyramidal: Outside of the pyramidal tracts. [EU] Extravasation: A discharge or escape, as of blood, from a vessel into the tissues. [EU] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [EU] Eye Infections: Infection, moderate to severe, caused by bacteria, fungi, or viruses, which occurs either on the external surface of the eye or intraocularly with probable inflammation, visual impairment, or blindness. [NIH] Facial: Of or pertaining to the face. [EU] Facial Paralysis: Severe or complete loss of facial muscle motor function. This condition may result from central or peripheral lesions. Damage to CNS motor pathways from the cerebral cortex to the facial nuclei in the pons leads to facial weakness that generally spares the forehead muscles. Facial nerve diseases generally results in generalized hemifacial weakness. Neuromuscular junction diseases and muscular diseases may also cause facial paralysis or paresis. [NIH] Faecal: Pertaining to or of the nature of feces. [EU] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Family Relations: Behavioral, psychological, and social relations among various members of the nuclear family and the extended family. [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] Febrile: Pertaining to or characterized by fever. [EU] Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] Feeding Behavior: Behavioral responses or sequences associated with eating including modes of feeding, rhythmic patterns of eating, and time intervals. [NIH] Fibrillation: A small, local, involuntary contraction of muscle, invisible under the skin, resulting from spontaneous activation of single muscle cells or muscle fibres. [EU] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of

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the blood clot. [NIH] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] Fibrinolytic: Pertaining to, characterized by, or causing the dissolution of fibrin by enzymatic action [EU] Fibrinolytic Agents: Fibrinolysin or agents that convert plasminogen to fibrinolysin (plasmin). [NIH] Fibroblast Growth Factor: Peptide isolated from the pituitary gland and from the brain. It is a potent mitogen which stimulates growth of a variety of mesodermal cells including chondrocytes, granulosa, and endothelial cells. The peptide may be active in wound healing and animal limb regeneration. [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] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral, anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] Flatus: Gas passed through the rectum. [NIH] Flexion: In gynaecology, a displacement of the uterus in which the organ is bent so far forward or backward that an acute angle forms between the fundus and the cervix. [EU] Flexor: Muscles which flex a joint. [NIH] Fluid Therapy: Therapy whose basic objective is to restore the volume and composition of the body fluids to normal with respect to water-electrolyte balance. Fluids may be administered intravenously, orally, by intermittent gavage, or by hypodermoclysis. [NIH] Flurothyl: A convulsant primarily used in experimental animals. It was formerly used to induce convulsions as a alternative to electroshock therapy. [NIH] Focus Groups: A method of data collection and a qualitative research tool in which a small group of individuals are brought together and allowed to interact in a discussion of their opinions about topics, issues, or questions. [NIH]

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Fold: A plication or doubling of various parts of the body. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Fossa: A cavity, depression, or pit. [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]

Fundus: The larger part of a hollow organ that is farthest away from the organ's opening. The bladder, gallbladder, stomach, uterus, eye, and cavity of the middle ear all have a fundus. [NIH] Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] Gait: Manner or style of walking. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gamma Rays: Very powerful and penetrating, high-energy electromagnetic radiation of shorter wavelength than that of x-rays. They are emitted by a decaying nucleus, usually between 0.01 and 10 MeV. They are also called nuclear x-rays. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Gap Junctions: Connections between cells which allow passage of small molecules and electric current. Gap junctions were first described anatomically as regions of close apposition between cells with a narrow (1-2 nm) gap between cell membranes. The variety in the properties of gap junctions is reflected in the number of connexins, the family of proteins which form the junctions. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gas exchange: Primary function of the lungs; transfer of oxygen from inhaled air into the blood and of carbon dioxide from the blood into the lungs. [NIH] Gastric: Having to do with the stomach. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories. [NIH]

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Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene 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 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] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Geriatric: Pertaining to the treatment of the aged. [EU] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glasgow Coma Scale: A scale that assesses the response to stimuli in patients with craniocerebral injuries. The parameters are eye opening, motor reponse, and verbal response. [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]

Glomerular Filtration Rate: The volume of water filtered out of plasma through glomerular capillary walls into Bowman's capsules per unit of time. It is considered to be equivalent to inulin clearance. [NIH] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Gluconeogenesis: The process by which glucose is formed from a non-carbohydrate source. [NIH]

Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH]

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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]

Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycogen: A sugar stored in the liver and muscles. It releases glucose into the blood when cells need it for energy. Glycogen is the chief source of stored fuel in the body. [NIH] Glycogen Synthase: An enzyme that catalyzes the transfer of D-glucose from UDPglucose into 1,4-alpha-D-glucosyl chains. EC 2.4.1.11. [NIH] Glycolysis: The pathway by which glucose is catabolized into two molecules of pyruvic acid with the generation of ATP. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycosaminoglycans: Heteropolysaccharides which contain an N-acetylated hexosamine in a characteristic repeating disaccharide unit. The repeating structure of each disaccharide involves alternate 1,4- and 1,3-linkages consisting of either N-acetylglucosamine or Nacetylgalactosamine. [NIH] Gonadal: Pertaining to a gonad. [EU] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Grading: A system for classifying cancer cells in terms of how abnormal they appear when examined under a microscope. The objective of a grading system is to provide information about the probable growth rate of the tumor and its tendency to spread. The systems used to grade tumors vary with each type of cancer. Grading plays a role in treatment decisions. [NIH]

Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Grafting: The operation of transfer of tissue from one site to another. [NIH] Granule: A small pill made from sucrose. [EU] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Gravis: Eruption of watery blisters on the skin among those handling animals and animal products. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [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] Haematemesis: The vomiting of blood. [EU]

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Haematoma: A localized collection of blood, usually clotted, in an organ, space, or tissue, due to a break in the wall of a blood vessel. [EU] Haemorrhage: The escape of blood from the vessels; bleeding. Small haemorrhages are classified according to size as petechiae (very small), purpura (up to 1 cm), and ecchymoses (larger). The massive accumulation of blood within a tissue is called a haematoma. [EU] Hallucinogen: A hallucination-producing drug, a category of drugs producing this effect. The user of a hallucinogenic drug is almost invariably aware that what he is seeing are hallucinations. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Headache Disorders: Common conditions characterized by persistent or recurrent headaches. Headache syndrome classification systems may be based on etiology (e.g., vascular headache, post-traumatic headaches, etc.), temporal pattern (e.g., cluster headache, paroxysmal hemicrania, etc.), and precipitating factors (e.g., cough headache). [NIH] Health Care Costs: The actual costs of providing services related to the delivery of health care, including the costs of procedures, therapies, and medications. It is differentiated from health expenditures, which refers to the amount of money paid for the services, and from fees, which refers to the amount charged, regardless of cost. [NIH] Health Expenditures: The amounts spent by individuals, groups, nations, or private or public organizations for total health care and/or its various components. These amounts may or may not be equivalent to the actual costs (health care costs) and may or may not be shared among the patient, insurers, and/or employers. [NIH] Health Resources: Available manpower, facilities, revenue, equipment, and supplies to produce requisite health care and services. [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] Hearing Disorders: Conditions that impair the transmission or perception of auditory impulses and information from the level of the ear to the temporal cortices, including the sensorineural pathways. [NIH] Heart Arrest: Sudden and usually momentary cessation of the heart beat. This sudden cessation may, but not usually, lead to death, sudden, cardiac. [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] Hematology: A subspecialty of internal medicine concerned with morphology, physiology, and pathology of the blood and blood-forming tissues. [NIH] Hematoma: An extravasation of blood localized in an organ, space, or tissue. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the

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prosthetic group in many hemeproteins. [NIH] Hemiparesis: The weakness or paralysis affecting one side of the body. [NIH] Hemodilution: Reduction of blood viscosity usually by the addition of cell free solutions. Used clinically l) in states of impaired microcirculation, 2) for replacement of intraoperative blood loss without homologous blood transfusion, and 3) in cardiopulmonary bypass and hypothermia. [NIH] Hemodynamics: The movements of the blood and the forces involved in systemic or regional blood circulation. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]

Hepatic: Refers to the liver. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]

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] Histology: The study of tissues and cells under a microscope. [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

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hormone deficiency. [NIH] Hormone therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called endocrine therapy. [NIH] Hospital Administration: Management of the internal organization of the hospital. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Housekeeping: The care and management of property. [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] Hydrocortisone: The main glucocorticoid secreted by the adrenal cortex. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic 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] Hygienic: Pertaining to hygiene, or conducive to health. [EU] Hyperalgesia: Excessive sensitiveness or sensibility to pain. [EU] Hypercapnia: A clinical manifestation of abnormal increase in the amount of carbon dioxide in arterial blood. [NIH] Hyperesthesia: Increased sensitivity to cutaneous stimulation due to a diminished threshold or an increased response to stimuli. [NIH] Hyperlipidaemia: A general term for elevated concentrations of any or all of the lipids in the plasma, including hyperlipoproteinaemia, hypercholesterolaemia, etc. [EU] Hyperoxia: An abnormal increase in the amount of oxygen in the tissues and organs. [NIH]

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Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hypertensive Encephalopathy: Brain dysfunction or damage resulting from malignant hypertension, usually associated with a diastolic blood pressure in excess of 125 mmHg. Clinical manifestations include headache, nausea, emesis, seizures, altered mental status (in some cases progressing to coma), papilledema, and retinal hemorrhage. Focal neurologic signs may develop. Pathologically, this condition may be associated with the formation of ischemic lesions in the brain (brain ischemia). [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] Hyperthyroidism: Excessive functional activity of the thyroid gland. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] 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] Hypoglycaemia: An abnormally diminished concentration of glucose in the blood, which may lead to tremulousness, cold sweat, piloerection, hypothermia, and headache, accompanied by irritability, confusion, hallucinations, bizarre behaviour, and ultimately, convulsions and coma. [EU] Hypoglycemia: Abnormally low blood sugar [NIH] Hypophysis: A remnant of the entodermal pouch of Rathke beneath the mucous membrane of the pharynx, which shows pituitary tissue. [NIH] Hypotension: Abnormally low blood pressure. [NIH] Hypothalamic: Of or involving the hypothalamus. [EU] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH] Hypothermia: Lower than normal body temperature, especially in warm-blooded animals; in man usually accidental or unintentional. [NIH] Hypothyroidism: Deficiency of thyroid activity. In adults, it is most common in women and is characterized by decrease in basal metabolic rate, tiredness and lethargy, sensitivity to cold, and menstrual disturbances. If untreated, it progresses to full-blown myxoedema. In infants, severe hypothyroidism leads to cretinism. In juveniles, the manifestations are intermediate, with less severe mental and developmental retardation and only mild symptoms of the adult form. When due to pituitary deficiency of thyrotropin secretion it is called secondary hypothyroidism. [EU] Hypotonic Solutions: Solutions that have a lesser osmotic pressure than a reference solution such as blood, plasma, or interstitial fluid. [NIH] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Ibotenic Acid: Neurotoxic isoxazole substance found in Amanita muscaria and A.

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pantherina. It causes motor depression, ataxia, and changes in mood, perceptions and feelings, and is a potent excitatory amino acid agonist. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Ileum: The lower end of the small intestine. [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] Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [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] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience 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] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] 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,

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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]

Infection Control: Programs of disease surveillance, generally within health care facilities, designed to investigate, prevent, and control the spread of infections and their causative microorganisms. [NIH] Infertility: The diminished or absent ability to conceive or produce an offspring while sterility is the complete inability to conceive or produce an offspring. [NIH] Infestation: Parasitic attack or subsistence on the skin and/or its appendages, as by insects, mites, or ticks; sometimes used to denote parasitic invasion of the organs and tissues, as by helminths. [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]

Influenza: An acute viral infection involving the respiratory tract. It is marked by inflammation of the nasal mucosa, the pharynx, and conjunctiva, and by headache and severe, often generalized, myalgia. [NIH] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Initiator: A chemically reactive substance which may cause cell changes if ingested, inhaled or absorbed into the body; the substance may thus initiate a carcinogenic process. [NIH] Inlay: In dentistry, a filling first made to correspond with the form of a dental cavity and then cemented into the cavity. [NIH] Innervation: 1. The distribution or supply of nerves to a part. 2. The supply of nervous energy or of nerve stimulus sent to a part. [EU] Inorganic: Pertaining to substances not of organic origin. [EU] Inositol: An isomer of glucose that has traditionally been considered to be a B vitamin although it has an uncertain status as a vitamin and a deficiency syndrome has not been identified in man. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1379) Inositol phospholipids are important in signal transduction. [NIH] Inotropic: Affecting the force or energy of muscular contractions. [EU] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH]

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Insomnia: Difficulty in going to sleep or getting enough sleep. [NIH] Instillation: . [EU] 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] Insulin-like: Muscular growth factor. [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] Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Interleukin-1: A soluble factor produced by monocytes, macrophages, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. IL-1 consists of two distinct forms, IL-1 alpha and IL-1 beta which perform the same functions but are distinct proteins. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. The factor is distinct from interleukin-2. [NIH] Interleukin-2: Chemical mediator produced by activated T lymphocytes and which regulates the proliferation of T cells, as well as playing a role in the regulation of NK cell activity. [NIH] Interleukin-6: Factor that stimulates the growth and differentiation of human B-cells and is also a growth factor for hybridomas and plasmacytomas. It is produced by many different cells including T-cells, monocytes, and fibroblasts. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intervertebral: Situated between two contiguous vertebrae. [EU] Intervertebral Disk Displacement: An intervertebral disk in which the nucleus pulposus has protruded through surrounding fibrocartilage. This occurs most frequently in the lower lumbar region. [NIH]

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Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intracranial Hypertension: Increased pressure within the cranial vault. This may result from several conditions, including hydrocephalus; brain edema; intracranial masses; severe systemic hypertension; pseudotumor cerebri; and other disorders. [NIH] Intracranial Pressure: Pressure within the cranial cavity. It is influenced by brain mass, the circulatory system, CSF dynamics, and skull rigidity. [NIH] Intramuscular: IM. Within or into muscle. [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] Iodine: A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126.90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. [NIH] Iodine-131: Radioactive isotope of iodine. [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] 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] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Irritable Bowel Syndrome: A disorder that comes and goes. Nerves that control the muscles in the GI tract are too active. The GI tract becomes sensitive to food, stool, gas, and stress. Causes abdominal pain, bloating, and constipation or diarrhea. Also called spastic colon or mucous colitis. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU]

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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] Isotonic: A biological term denoting a solution in which body cells can be bathed without a net flow of water across the semipermeable cell membrane. Also, denoting a solution having the same tonicity as some other solution with which it is compared, such as physiologic salt solution and the blood serum. [EU] Jejunum: That portion of the small intestine which extends from the duodenum to the ileum; called also intestinum jejunum. [EU] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kainate: Glutamate receptor. [NIH] Kainic Acid: (2S-(2 alpha,3 beta,4 beta))-2-Carboxy-4-(1-methylethenyl)-3-pyrrolidineacetic acid. Ascaricide obtained from the red alga Digenea simplex. It is a potent excitatory amino acid agonist at some types of excitatory amino acid receptors and has been used to discriminate among receptor types. Like many excitatory amino acid agonists it can cause neurotoxicity and has been used experimentally for that purpose. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Keratolytic: An agent that promotes keratolysis. [EU] Ketamine: A cyclohexanone derivative used for induction of anesthesia. Its mechanism of action is not well understood, but ketamine can block NMDA receptors (receptors, NMethyl-D-Aspartate) and may interact with sigma receptors. [NIH] 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] Kinetic: Pertaining to or producing motion. [EU] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Laminin: Large, noncollagenous glycoprotein with antigenic properties. It is localized in the basement membrane lamina lucida and functions to bind epithelial cells to the basement membrane. Evidence suggests that the protein plays a role in tumor invasion. [NIH] Language Development: The gradual expansion in complexity and meaning of symbols and sounds as perceived and interpreted by the individual through a maturational and learning process. Stages in development include babbling, cooing, word imitation with cognition, and use of short sentences. [NIH] Language Development Disorders: Conditions characterized by language abilities (comprehension and expression of speech and writing) that are below the expected level for

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a given age, generally in the absence of an intellectual impairment. These conditions may be associated with deafness; brain diseases; mental disorders; or environmental factors. [NIH] Language Disorders: Conditions characterized by deficiencies of comprehension or expression of written and spoken forms of language. These include acquired and developmental disorders. [NIH] Language Therapy: Rehabilitation of persons with language disorders or training of children with language development disorders. [NIH] Laparoscopy: Examination, therapy or surgery of the abdomen's interior by means of a laparoscope. [NIH] Larynx: An irregularly shaped, musculocartilaginous tubular structure, lined with mucous membrane, located at the top of the trachea and below the root of the tongue and the hyoid bone. It is the essential sphincter guarding the entrance into the trachea and functioning secondarily as the organ of voice. [NIH] Latency: The period of apparent inactivity between the time when a stimulus is presented and the moment a response occurs. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Latent period: A seemingly inactive period, as that between exposure of tissue to an injurious agent and the manifestation of response, or that between the instant of stimulation and the beginning of response. [EU] Length of Stay: The period of confinement of a patient to a hospital or other health facility. [NIH]

Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] Lethargy: Abnormal drowsiness or stupor; a condition of indifference. [EU] Leucocyte: All the white cells of the blood and their precursors (myeloid cell series, lymphoid cell series) but commonly used to indicate granulocytes exclusive of lymphocytes. [NIH]

Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Leukopenia: A condition in which the number of leukocytes (white blood cells) in the blood is reduced. [NIH] Leukotrienes: A family of biologically active compounds derived from arachidonic acid by oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal tract and the immune system. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]

Lice: A general name for small, wingless, parasitic insects, previously of the order Phthiraptera. Though exact taxonomy is still controversial, they can be grouped in the orders Anoplura (sucking lice), Mallophaga (biting lice), and Rhynchophthirina (elephant

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lice). [NIH] Life cycle: The successive stages through which an organism passes from fertilized ovum or spore to the fertilized ovum or spore of the next generation. [NIH] Life Expectancy: A figure representing the number of years, based on known statistics, to which any person of a given age may reasonably expect to live. [NIH] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Ligands: A RNA simulation method developed by the MIT. [NIH] Limbic: Pertaining to a limbus, or margin; forming a border around. [EU] Limbic System: A set of forebrain structures common to all mammals that is defined functionally and anatomically. It is implicated in the higher integration of visceral, olfactory, and somatic information as well as homeostatic responses including fundamental survival behaviors (feeding, mating, emotion). For most authors, it includes the amygdala, epithalamus, gyrus cinguli, hippocampal formation (see hippocampus), hypothalamus, parahippocampal gyrus, septal nuclei, anterior nuclear group of thalamus, and portions of the basal ganglia. (Parent, Carpenter's Human Neuroanatomy, 9th ed, p744; NeuroNames, http://rprcsgi.rprc.washington.edu/neuronames/index.html (September 2, 1998)). [NIH] 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] Lipid: Fat. [NIH] Lipid A: Lipid A is the biologically active component of lipopolysaccharides. It shows strong endotoxic activity and exhibits immunogenic properties. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipopolysaccharides: Substance consisting of polysaccaride and lipid. [NIH] Lipoxygenase: An enzyme of the oxidoreductase class that catalyzes reactions between linoleate and other fatty acids and oxygen to form hydroperoxy-fatty acid derivatives. Related enzymes in this class include the arachidonate lipoxygenases, arachidonate 5lipoxygenase, arachidonate 12-lipoxygenase, and arachidonate 15-lipoxygenase. EC 1.13.11.12. [NIH] Lipoxygenase Inhibitors: Compounds or agents that combine with lipoxygenase and thereby prevent its substrate-enzyme combination with arachidonic acid and the formation of the eicosanoid products hydroxyeicosatetraenoic acid and various leukotrienes. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver scan: An image of the liver created on a computer screen or on film. A radioactive substance is injected into a blood vessel and travels through the bloodstream. It collects in the liver, especially in abnormal areas, and can be detected by the scanner. [NIH] 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] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH]

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Locomotor: Of or pertaining to locomotion; pertaining to or affecting the locomotive apparatus of the body. [EU] Locus Coeruleus: Bluish region in the superior angle of the fourth ventricle floor, corresponding to melanin-like pigmented nerve cells which lie lateral to the pontomesencephalic central gray (griseum centrale). It is also known as nucleus pigmentosus pontis. [NIH] Longitudinal study: Also referred to as a "cohort study" or "prospective study"; the analytic method of epidemiologic study in which subsets of a defined population can be identified who are, have been, or in the future may be exposed or not exposed, or exposed in different degrees, to a factor or factors hypothesized to influence the probability of occurrence of a given disease or other outcome. The main feature of this type of study is to observe large numbers of subjects over an extended time, with comparisons of incidence rates in groups that differ in exposure levels. [NIH] Long-Term Care: Care over an extended period, usually for a chronic condition or disability, requiring periodic, intermittent, or continuous care. [NIH] Long-Term Potentiation: A persistent increase in synaptic efficacy, usually induced by appropriate activation of the same synapses. The phenomenological properties of long-term potentiation suggest that it may be a cellular mechanism of learning and memory. [NIH] Low Back Pain: Acute or chronic pain in the lumbar or sacral regions, which may be associated with musculo-ligamentous sprains and strains; intervertebral disk displacement; and other conditions. [NIH] Lucida: An instrument, invented by Wollaton, consisting essentially of a prism or a mirror through which an object can be viewed so as to appear on a plane surface seen in direct view and on which the outline of the object may be traced. [NIH] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] Lung volume: The amount of air the lungs hold. [NIH] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] 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]

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] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] 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] Macula: A stain, spot, or thickening. Often used alone to refer to the macula retinae. [EU]

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Macula Lutea: An oval area in the retina, 3 to 5 mm in diameter, usually located temporal to the superior pole of the eye and slightly below the level of the optic disk. [NIH] Macular Degeneration: Degenerative changes in the macula lutea of the retina. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Magnetic Resonance Spectroscopy: Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (magnetic resonance imaging). [NIH] Malaria: A protozoan disease caused in humans by four species of the genus Plasmodium (P. falciparum (malaria, falciparum), P. vivax (malaria, vivax), P. ovale, and P. malariae) and transmitted by the bite of an infected female mosquito of the genus Anopheles. Malaria is endemic in parts of Asia, Africa, Central and South America, Oceania, and certain Caribbean islands. It is characterized by extreme exhaustion associated with paroxysms of high fever, sweating, shaking chills, and anemia. Malaria in animals is caused by other species of plasmodia. [NIH] Malaria, Falciparum: Malaria caused by Plasmodium falciparum. This is the severest form of malaria and is associated with the highest levels of parasites in the blood. This disease is characterized by irregularly recurring febrile paroxysms that in extreme cases occur with acute cerebral, renal, or gastrointestinal manifestations. [NIH] Malaria, Vivax: Malaria caused by Plasmodium vivax. This form of malaria is less severe than malaria, falciparum, but there is a higher probability for relapses to occur. Febrile paroxysms often occur every other day. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant tumor: A tumor capable of metastasizing. [NIH] Malingering: Simulation of symptoms of illness or injury with intent to deceive in order to obtain a goal, e.g., a claim of physical illness to avoid jury duty. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]

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] Manic: Affected with mania. [EU] Manic-depressive psychosis: One of a group of psychotic reactions, fundamentally marked by severe mood swings and a tendency to remission and recurrence. [NIH] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Mannitol: A diuretic and renal diagnostic aid related to sorbitol. It has little significant energy value as it is largely eliminated from the body before any metabolism can take place. It can be used to treat oliguria associated with kidney failure or other manifestations of inadequate renal function and has been used for determination of glomerular filtration rate. Mannitol is also commonly used as a research tool in cell biological studies, usually to

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control osmolarity. [NIH] Mastication: The act and process of chewing and grinding food in the mouth. [NIH] Matrix metalloproteinase: A member of a group of enzymes that can break down proteins, such as collagen, that are normally found in the spaces between cells in tissues (i.e., extracellular matrix proteins). Because these enzymes need zinc or calcium atoms to work properly, they are called metalloproteinases. Matrix metalloproteinases are involved in wound healing, angiogenesis, and tumor cell metastasis. [NIH] Meatus: A canal running from the internal auditory foramen through the petrous portion of the temporal bone. It gives passage to the facial and auditory nerves together with the auditory branch of the basilar artery and the internal auditory veins. [NIH] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] 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] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Melanin: The substance that gives the skin its color. [NIH] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Memory Disorders: Disturbances in registering an impression, in the retention of an acquired impression, or in the recall of an impression. Memory impairments are associated with dementia; craniocerebraltrauma; encephalitis; alcoholism (see also alcohol amnestic disorder); schizophrenia; and other conditions. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Meningitis: Inflammation of the meninges. When it affects the dura mater, the disease is termed pachymeningitis; when the arachnoid and pia mater are involved, it is called leptomeningitis, or meningitis proper. [EU] Menopause: Permanent cessation of menstruation. [NIH] Menstrual Cycle: The period of the regularly recurring physiologic changes in the

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endometrium occurring during the reproductive period in human females and some primates and culminating in partial sloughing of the endometrium (menstruation). [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mental Processes: Conceptual functions or thinking in all its forms. [NIH] Mental Retardation: Refers to sub-average general intellectual functioning which originated during the developmental period and is associated with impairment in adaptive behavior. [NIH]

Mentors: Senior professionals who provide guidance, direction and support to those persons desirous of improvement in academic positions, administrative positions or other career development situations. [NIH] Mesencephalic: Ipsilateral oculomotor paralysis and contralateral tremor, spasm. or choreic movements of the face and limbs. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metabotropic: A glutamate receptor which triggers an increase in production of 2 intracellular messengers: diacylglycerol and inositol 1, 4, 5-triphosphate. [NIH] 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] Metatarsophalangeal Joint: The articulation between a metatarsal bone and a phalanx. [NIH] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [NIH] Methylphenidate: A central nervous system stimulant used most commonly in the treatment of attention-deficit disorders in children and for narcolepsy. Its mechanisms appear to be similar to those of dextroamphetamine. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microcirculation: The vascular network lying between the arterioles and venules; includes capillaries, metarterioles and arteriovenous anastomoses. Also, the flow of blood through this network. [NIH] Microdialysis: A technique for measuring extracellular concentrations of substances in tissues, usually in vivo, by means of a small probe equipped with a semipermeable membrane. Substances may also be introduced into the extracellular space through the membrane. [NIH] Micronutrients: Essential dietary elements or organic compounds that are required in only small quantities for normal physiologic processes to occur. [NIH]

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Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Micro-organism: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Microtubule-Associated Proteins: High molecular weight proteins found in the microtubules of the cytoskeletal system. Under certain conditions they are required for tubulin assembly into the microtubules and stabilize the assembled microtubules. [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] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] 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] Mobilization: The process of making a fixed part or stored substance mobile, as by separating a part from surrounding structures to make it accessible for an operative procedure or by causing release into the circulation for body use of a substance stored in the body. [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

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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] Monophosphate: So called second messenger for neurotransmitters and hormones. [NIH] Mood Disorders: Those disorders that have a disturbance in mood as their predominant feature. [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 forms of life). [NIH] Motility: The ability to move spontaneously. [EU] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness, and air sickness. [NIH] Motor Activity: The physical activity of an organism as a behavioral phenomenon. [NIH] Motor nerve: An efferent nerve conveying an impulse that excites muscular contraction. [NIH]

Motor Neurons: Neurons which activate muscle cells. [NIH] Motor Skills: Performance of complex motor acts. [NIH] Movement Disorders: Syndromes which feature dyskinesias as a cardinal manifestation of the disease process. Included in this category are degenerative, hereditary, post-infectious, medication-induced, post-inflammatory, and post-traumatic conditions. [NIH] 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] Mucolytic: Destroying or dissolving mucin; an agent that so acts : a mucopolysaccharide or glycoprotein, the chief constituent of mucus. [EU] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Multiple Myeloma: A malignant tumor of plasma cells usually arising in the bone marrow; characterized by diffuse involvement of the skeletal system, hyperglobulinemia, Bence-Jones proteinuria, and anemia. [NIH] Multiple Organ Failure: A progressive condition usually characterized by combined failure of several organs such as the lungs, liver, kidney, along with some clotting mechanisms, usually postinjury or postoperative. [NIH] Multiple sclerosis: A disorder of the central nervous system marked by weakness, numbness, a loss of muscle coordination, and problems with vision, speech, and bladder control. Multiple sclerosis is thought to be an autoimmune disease in which the body's immune system destroys myelin. Myelin is a substance that contains both protein and fat (lipid) and serves as a nerve insulator and helps in the transmission of nerve signals. [NIH] Multiple Trauma: Physical insults or injuries occurring simultaneously in several parts of the body. [NIH] Muscle Relaxation: That phase of a muscle twitch during which a muscle returns to a resting position. [NIH] Muscular Diseases: Acquired, familial, and congenital disorders of skeletal muscle and smooth muscle. [NIH]

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Musculature: The muscular apparatus of the body, or of any part of it. [EU] Musculoskeletal System: Themuscles, bones, and cartilage of the body. [NIH] Myalgia: Pain in a muscle or muscles. [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] Myelodysplastic syndrome: Disease in which the bone marrow does not function normally. Also called preleukemia or smoldering leukemia. [NIH] Myelogenous: Produced by, or originating in, the bone marrow. [NIH] Myeloma: Cancer that arises in plasma cells, a type of white blood cell. [NIH] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocardial Ischemia: A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (coronary arteriosclerosis), to obstruction by a thrombus (coronary thrombosis), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result in necrosis of cardiac muscle (myocardial infarction). [NIH] Myocardial Reperfusion: Generally, restoration of blood supply to heart 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. Reperfusion can be induced to treat ischemia. Methods include chemical dissolution of an occluding thrombus, administration of vasodilator drugs, angioplasty, catheterization, and artery bypass graft surgery. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing myocardial reperfusion injury. [NIH] Myocardial Reperfusion Injury: Functional, metabolic, or structural changes in ischemic heart muscle thought to result from reperfusion to the ischemic areas. Changes can be fatal to muscle cells and may include edema with explosive cell swelling and disintegration, sarcolemma disruption, fragmentation of mitochondria, contraction band necrosis, enzyme washout, and calcium overload. Other damage may include hemorrhage and ventricular arrhythmias. One possible mechanism of damage is thought to be oxygen free radicals. Treatment currently includes the introduction of scavengers of oxygen free radicals, and injury is thought to be prevented by warm blood cardioplegic infusion prior to reperfusion. [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] N-acetyl: Analgesic agent. [NIH] Narcolepsy: A condition of unknown cause characterized by a periodic uncontrollable tendency to fall asleep. [NIH] Nasal Mucosa: The mucous membrane lining the nasal cavity. [NIH] Nasopharynx: The nasal part of the pharynx, lying above the level of the soft palate. [NIH]

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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] Neck Pain: Discomfort or more intense forms of pain that are localized to the cervical region. This term generally refers to pain in the posterior or lateral regions of the neck. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Neocortex: The largest portion of the cerebral cortex. It is composed of neurons arranged in six layers. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neoplasms: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Nephropathy: Disease of the kidneys. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nerve Endings: Specialized terminations of peripheral neurons. Nerve endings include neuroeffector junction(s) by which neurons activate target organs and sensory receptors which transduce information from the various sensory modalities and send it centrally in the nervous system. Presynaptic nerve endings are presynaptic terminals. [NIH] Nerve Fibers: Slender processes of neurons, especially the prolonged axons that conduct nerve impulses. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] 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] Neural Pathways: Neural tracts connecting one part of the nervous system with another. [NIH]

Neuralgia: Intense or aching pain that occurs along the course or distribution of a peripheral or cranial nerve. [NIH] Neurasthenia: A mental disorder characterized by chronic fatigue and concomitant physiologic symptoms. [NIH] Neuroanatomy: Study of the anatomy of the nervous system as a specialty or discipline. [NIH]

Neurobehavioral Manifestations: Signs and symptoms of higher cortical dysfunction caused by organic conditions. These include certain behavioral alterations and impairments of skills involved in the acquisition, processing, and utilization of knowledge or information. [NIH]

Neurodegenerative Diseases: Hereditary and sporadic conditions which are characterized

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by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures. [NIH] Neuroendocrine: Having to do with the interactions between the nervous system and the endocrine system. Describes certain cells that release hormones into the blood in response to stimulation of the nervous system. [NIH] Neuroendocrinology: The study of the anatomical and functional relationships between the nervous system and the endocrine system. [NIH] Neurofibrillary Tangles: Abnormal structures located in various parts of the brain and composed of dense arrays of paired helical filaments (neurofilaments and microtubules). These double helical stacks of transverse subunits are twisted into left-handed ribbon-like filaments that likely incorporate the following proteins: (1) the intermediate filaments: medium- and high-molecular-weight neurofilaments; (2) the microtubule-associated proteins map-2 and tau; (3) actin; and (4) ubiquitin. As one of the hallmarks of Alzheimer disease, the neurofibrillary tangles eventually occupy the whole of the cytoplasm in certain classes of cell in the neocortex, hippocampus, brain stem, and diencephalon. The number of these tangles, as seen in post mortem histology, correlates with the degree of dementia during life. Some studies suggest that tangle antigens leak into the systemic circulation both in the course of normal aging and in cases of Alzheimer disease. [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] Neuroleptic: A term coined to refer to the effects on cognition and behaviour of antipsychotic drugs, which produce a state of apathy, lack of initiative, and limited range of emotion and in psychotic patients cause a reduction in confusion and agitation and normalization of psychomotor activity. [EU] Neurologic: Having to do with nerves or the nervous system. [NIH] Neurology: A medical specialty concerned with the study of the structures, functions, and diseases of the nervous system. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Blockade: The intentional interruption of transmission at the neuromuscular junction by external agents, usually neuromuscular blocking agents. It is distinguished from nerve block in which nerve conduction is interrupted rather than neuromuscular transmission. Neuromuscular blockade is commonly used to produce muscle relaxation as an adjunct to anesthesia during surgery and other medical procedures. It is also often used as an experimental manipulation in basic research. It is not strictly speaking anesthesia but is grouped here with anesthetic techniques. The failure of neuromuscular transmission as a result of pathological processes is not included here. [NIH] 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,

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and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropeptide: A member of a class of protein-like molecules made in the brain. Neuropeptides consist of short chains of amino acids, with some functioning as neurotransmitters and some functioning as hormones. [NIH] Neurophysiology: The scientific discipline concerned with the physiology of the nervous system. [NIH] Neuropil: A dense intricate feltwork of interwoven fine glial processes, fibrils, synaptic terminals, axons, and dendrites interspersed among the nerve cells in the gray matter of the central nervous system. [NIH] Neuropil Threads: Abnormal structures located chiefly in distal dendrites and, along with neurofibrillary tangles and senile plaques, constitute the three morphological hallmarks of Alzheimer disease. Neuropil threads are made up of straight and paired helical filaments which consist of abnormally phosphorylated microtubule-associated tau proteins. It has been suggested that the threads have a major role in the cognitive impairment seen in Alzheimer disease. [NIH] Neuroprotective Agents: Drugs intended to prevent damage to the brain or spinal cord from ischemia, stroke, convulsions, or trauma. Some must be administered before the event, but others may be effective for some time after. They act by a variety of mechanisms, but often directly or indirectly minimize the damage produced by endogenous excitatory amino acids. [NIH] Neuropsychological Tests: Tests designed to assess neurological function associated with certain behaviors. They are used in diagnosing brain dysfunction or damage and central nervous system disorders or injury. [NIH] Neuropsychology: A branch of psychology which investigates the correlation between experience or behavior and the basic neurophysiological processes. The term neuropsychology stresses the dominant role of the nervous system. It is a more narrowly defined field than physiological psychology or psychophysiology. [NIH] Neurosciences: The scientific disciplines concerned with the embryology, anatomy, physiology, biochemistry, pharmacology, etc., of the nervous sytem. [NIH] Neurosis: Functional derangement due to disorders of the nervous system which does not affect the psychic personality of the patient. [NIH] Neurosurgeon: A doctor who specializes in surgery on the brain, spine, and other parts of the nervous system. [NIH] Neurosurgery: A surgical specialty concerned with the treatment of diseases and disorders of the brain, spinal cord, and peripheral and sympathetic nervous system. [NIH] Neurotic: 1. Pertaining to or characterized by neurosis. 2. A person affected with a neurosis. [EU]

Neurotoxic: Poisonous or destructive to nerve tissue. [EU] Neurotoxicity: The tendency of some treatments to cause damage to the nervous system. [NIH]

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

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acting at synapses. [NIH] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutrophil: A type of white blood cell. [NIH] Neutrophil Activation: The process in which the neutrophil is stimulated by diverse substances, resulting in degranulation and/or generation of reactive oxygen products, and culminating in the destruction of invading pathogens. The stimulatory substances, including opsonized particles, immune complexes, and chemotactic factors, bind to specific cellsurface receptors on the neutrophil. [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] Nimodipine: A calcium channel blockader with preferential cerebrovascular activity. It has marked cerebrovascular dilating effects and lowers blood pressure. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]

Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Nitrogen Dioxide: Nitrogen oxide (NO2). A highly poisonous gas. Exposure produces inflammation of lungs that may only cause slight pain or pass unnoticed, but resulting edema several days later may cause death. (From Merck, 11th ed) It is a major atmospheric pollutant that is able to absorb UV light that does not reach the earth's surface. [NIH] Nitrogen Oxides: Inorganic oxides that contain nitrogen. [NIH] Nociceptors: Peripheral receptors for pain. Nociceptors include receptors which are sensitive to painful mechanical stimuli, extreme heat or cold, and chemical stimuli. All nociceptors are free nerve endings. [NIH] Nonverbal Communication: Transmission of emotions, ideas, and attitudes between individuals in ways other than the spoken language. [NIH] Nordihydroguaiaretic Acid: A potent lipoxygenase inhibitor that interferes with arachidonic acid metabolism. The compound also inhibits formyltetrahydrofolate synthetase, carboxylesterase, and cyclooxygenase to a lesser extent. It also serves as an antioxidant in fats and oils. [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]

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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] Nuclear Family: A family composed of spouses and their children. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleolus: A small dense body (sub organelle) within the nucleus of eukaryotic cells, visible by phase contrast and interference microscopy in live cells throughout interphase. Contains RNA and protein and is the site of synthesis of ribosomal RNA. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nursing Care: Care given to patients by nursing service personnel. [NIH] Nutritional Support: The administration of nutrients for assimilation and utilization by a patient by means other than normal eating. It does not include fluid therapy which normalizes body fluids to restore water-electrolyte balance. [NIH] Observer Variation: The failure by the observer to measure or identify a phenomenon accurately, which results in an error. Sources for this may be due to the observer's missing an abnormality, or to faulty technique resulting in incorrect test measurement, or to misinterpretation of the data. Two varieties are inter-observer variation (the amount observers vary from one another when reporting on the same material) and intra-observer variation (the amount one observer varies between observations when reporting more than once on the same material). [NIH] Occult: Obscure; concealed from observation, difficult to understand. [EU] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Oculomotor: Cranial nerve III. It originate from the lower ventral surface of the midbrain and is classified as a motor nerve. [NIH] 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] Oligomenorrhea: Abnormally infrequent menstruation. [NIH] Oliguria: Clinical manifestation of the urinary system consisting of a decrease in the amount of urine secreted. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Operating Rooms: Facilities equipped for performing surgery. [NIH] Opsin: A protein formed, together with retinene, by the chemical breakdown of metarhodopsin. [NIH] Optic Chiasm: The X-shaped structure formed by the meeting of the two optic nerves. At the optic chiasm the fibers from the medial part of each retina cross to project to the other side of the brain while the lateral retinal fibers continue on the same side. As a result each half of the brain receives information about the contralateral visual field from both eyes. [NIH]

Optic Disk: The portion of the optic nerve seen in the fundus with the ophthalmoscope. It is

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formed by the meeting of all the retinal ganglion cell axons as they enter the optic nerve. [NIH]

Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Orthopaedic: Pertaining to the correction of deformities of the musculoskeletal system; pertaining to orthopaedics. [EU] Orthotic Devices: Apparatus used to support, align, prevent, or correct deformities or to improve the function of movable parts of the body. [NIH] Osmolarity: The concentration of osmotically active particles expressed in terms of osmoles of solute per litre of solution. [EU] Osmosis: Tendency of fluids (e.g., water) to move from the less concentrated to the more concentrated side of a semipermeable membrane. [NIH] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] Osteoarthritis: A progressive, degenerative joint disease, the most common form of arthritis, especially in older persons. The disease is thought to result not from the aging process but from biochemical changes and biomechanical stresses affecting articular cartilage. In the foreign literature it is often called osteoarthrosis deformans. [NIH] Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [NIH] 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] 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] Overexpress: An excess of a particular protein on the surface of a cell. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] 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]

Oxidative metabolism: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as aerobic respiration, cell respiration, or aerobic metabolism. [NIH] 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

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bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Oxides: Binary compounds of oxygen containing the anion O(2-). The anion combines with metals to form alkaline oxides and non-metals to form acidic oxides. [NIH] Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Oxygenase: Enzyme which breaks down heme, the iron-containing oxygen-carrying constituent of the red blood cells. [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] Pachymeningitis: Inflammation of the dura mater of the brain, the spinal cord or the optic nerve. [NIH] Paediatric: Of or relating to the care and medical treatment of children; belonging to or concerned with paediatrics. [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] Pancreatitis: Acute or chronic inflammation of the pancreas, which may be asymptomatic or symptomatic, and which is due to autodigestion of a pancreatic tissue by its own enzymes. It is caused most often by alcoholism or biliary tract disease; less commonly it may be associated with hyperlipaemia, hyperparathyroidism, abdominal trauma (accidental or operative injury), vasculitis, or uraemia. [EU] Papilledema: Swelling around the optic disk. [NIH] Paraganglia, Chromaffin: Small bodies containing chromaffin cells occurring outside of the adrenal medulla, most commonly near the sympathetic ganglia and in organs such as the kidney, liver, heart and gonads. [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]

Parasitic: Having to do with or being a parasite. A parasite is an animal or a plant that lives on or in an organism of another species and gets at least some of its nutrients from it. [NIH] Parenchyma: The essential elements of an organ; used in anatomical nomenclature as a general term to designate the functional elements of an organ, as distinguished from its

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framework, or stroma. [EU] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Parenteral Nutrition: The administering of nutrients for assimilation and utilization by a patient who cannot maintain adequate nutrition by enteral feeding alone. Nutrients are administered by a route other than the alimentary canal (e.g., intravenously, subcutaneously). [NIH] Paresis: A general term referring to a mild to moderate degree of muscular weakness, occasionally used as a synonym for paralysis (severe or complete loss of motor function). In the older literature, paresis often referred specifically to paretic neurosyphilis. "General paresis" and "general paralysis" may still carry that connotation. Bilateral lower extremity paresis is referred to as paraparesis. [NIH] 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] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Partial response: A decrease in the size of a tumor, or in the extent of cancer in the body, in response to treatment. [NIH] 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 Education: The teaching or training of patients concerning their own health needs. [NIH]

Pediculosis: Infestation with lice of the family Pediculidae, especially infestation with Pediculus humanus. [EU] Penis: The external reproductive organ of males. It is composed of a mass of erectile tissue enclosed in three cylindrical fibrous compartments. Two of the three compartments, the corpus cavernosa, are placed side-by-side along the upper part of the organ. The third compartment below, the corpus spongiosum, houses the urethra. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Perception: The ability quickly and accurately to recognize similarities and differences among presented objects, whether these be pairs of words, pairs of number series, or multiple sets of these or other symbols such as geometric figures. [NIH] 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]

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Perennial: Lasting through the year of for several years. [EU] Perforation: 1. The act of boring or piercing through a part. 2. A hole made through a part or substance. [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] 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 blood: Blood circulating throughout the body. [NIH] Peripheral Nerves: The nerves outside of the brain and spinal cord, including the autonomic, cranial, and spinal nerves. Peripheral nerves contain non-neuronal cells and connective tissue as well as axons. The connective tissue layers include, from the outside to the inside, the epineurium, the perineurium, and the endoneurium. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] 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 mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal layer of the bowel wall. [NIH] Peritonitis: Inflammation of the peritoneum; a condition marked by exudations in the peritoneum of serum, fibrin, cells, and pus. It is attended by abdominal pain and tenderness, constipation, vomiting, and moderate fever. [EU] Perivascular: Situated around a vessel. [EU] Peroneal Nerve: The lateral of the two terminal branches of the sciatic nerve. The peroneal (or fibular) nerve provides motor and sensory innervation to parts of the leg and foot. [NIH] Petechiae: Pinpoint, unraised, round red spots under the skin caused by bleeding. [NIH] PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [EU] Phagocytosis: The engulfing of microorganisms, other cells, and foreign particles by phagocytic cells. [NIH] Pharmacodynamic: Is concerned with the response of living tissues to chemical stimuli, that is, the action of drugs on the living organism in the absence of disease. [NIH] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] 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] Pharyngitis: Inflammation of the throat. [NIH] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top

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of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] Phencyclidine: A hallucinogen formerly used as a veterinary anesthetic, and briefly as a general anesthetic for humans. Phencyclidine is similar to ketamine in structure and in many of its effects. Like ketamine, it can produce a dissociative state. It exerts its pharmacological action through inhibition of NMDA receptors (receptors, N-methyl-Daspartate). As a drug of abuse, it is known as PCP and Angel Dust. [NIH] 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] Phosphodiesterase: Effector enzyme that regulates the levels of a second messenger, the cyclic GMP. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] 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] Phosphorylated: Attached to a phosphate group. [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] 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] Physical Therapy: The restoration of function and the prevention of disability following disease or injury with the use of light, heat, cold, water, electricity, ultrasound, and exercise. [NIH]

Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Pitch: The subjective awareness of the frequency or spectral distribution of a sound. [NIH]

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Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Pituitary Hormones: Hormones secreted by the anterior and posterior lobes of the pituitary gland and the pars intermedia, an ill-defined region between the two. Their secretion is regulated by the hypothalamus. [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] Plague: An acute infectious disease caused by Yersinia pestis that affects humans, wild rodents, and their ectoparasites. This condition persists due to its firm entrenchment in sylvatic rodent-flea ecosystems throughout the world. Bubonic plague is the most common form. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma 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] Plasmin: A product of the lysis of plasminogen (profibrinolysin) by plasminogen activators. It is composed of two polypeptide chains, light (B) and heavy (A), with a molecular weight of 75,000. It is the major proteolytic enzyme involved in blood clot retraction or the lysis of fibrin and quickly inactivated by antiplasmins. EC 3.4.21.7. [NIH] Plasminogen: Precursor of fibrinolysin (plasmin). It is a single-chain beta-globulin of molecular weight 80-90,000 found mostly in association with fibrinogen in plasma; plasminogen activators change it to fibrinolysin. It is used in wound debriding and has been investigated as a thrombolytic agent. [NIH] Plasminogen Activators: A heterogeneous group of proteolytic enzymes that convert plasminogen to plasmin. They are concentrated in the lysosomes of most cells and in the vascular endothelium, particularly in the vessels of the microcirculation. EC 3.4.21.-. [NIH] Plasticity: In an individual or a population, the capacity for adaptation: a) through gene changes (genetic plasticity) or b) through internal physiological modifications in response to changes of environment (physiological plasticity). [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form.

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Also called thrombocytes. [NIH] Plexus: A network or tangle; a general term for a network of lymphatic vessels, nerves, or veins. [EU] 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] Polycystic Ovary Syndrome: Clinical symptom complex characterized by oligomenorrhea or amenorrhea, anovulation, and regularly associated with bilateral polycystic ovaries. [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Pons: The part of the central nervous system lying between the medulla oblongata and the mesencephalon, ventral to the cerebellum, and consisting of a pars dorsalis and a pars ventralis. [NIH] 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] 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] Postherpetic Neuralgia: Variety of neuralgia associated with migraine in which pain is felt in or behind the eye. [NIH] 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] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-traumatic: Occurring as a result of or after injury. [EU] Post-traumatic stress disorder: A psychological disorder that develops in some individuals after a major traumatic experience such as war, rape, domestic violence, or accident. [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] Potassium Channels: Cell membrane glycoproteins selective for potassium ions. [NIH] Potentiate: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH]

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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] Predictive factor: A situation or condition that may increase a person's risk of developing a certain disease or disorder. [NIH] 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] Pregnenolone: Steroid hormone. [NIH] Preleukemia: Conditions in which the abnormalities in the peripheral blood or bone marrow represent the early manifestations of acute leukemia, but in which the changes are not of sufficient magnitude or specificity to permit a diagnosis of acute leukemia by the usual clinical criteria. [NIH] Premedication: Preliminary administration of a drug preceding a diagnostic, therapeutic, or surgical procedure. The commonest types of premedication are antibiotics (antibiotic prophylaxis) and anti-anxiety agents. It does not include preanesthetic medication. [NIH] Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] 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] Priapism: Persistent abnormal erection of the penis, usually without sexual desire, and accompanied by pain and tenderness. It is seen in diseases and injuries of the spinal cord, and may be caused by vesical calculus and certain injuries to the penis. [EU] 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] Problem Solving: A learning situation involving more than one alternative from which a selection is made in order to attain a specific goal. [NIH] Prodrug: A substance that gives rise to a pharmacologically active metabolite, although not itself active (i. e. an inactive precursor). [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body,

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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] Progestogen: A term applied to any substance possessing progestational activity. [EU] Prognostic factor: A situation or condition, or a characteristic of a patient, that can be used to estimate the chance of recovery from a disease, or the chance of the disease recurring (coming back). [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Prolactin: Pituitary lactogenic hormone. A polypeptide hormone with a molecular weight of about 23,000. It is essential in the induction of lactation in mammals at parturition and is synergistic with estrogen. The hormone also brings about the release of progesterone from lutein cells, which renders the uterine mucosa suited for the embedding of the ovum should fertilization occur. [NIH] 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] Propofol: A widely used anesthetic. [NIH] Proportional: Being in proportion : corresponding in size, degree, or intensity, having the same or a constant ratio; of, relating to, or used in determining proportions. [EU] Prospective 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

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cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] Prostaglandin Endoperoxides: Precursors in the biosynthesis of prostaglandins and thromboxanes from arachidonic acid. They are physiologically active compounds, having effect on vascular and airway smooth muscles, platelet aggregation, etc. [NIH] Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [NIH] 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] Prostate gland: A gland in the male reproductive system just below the bladder. It surrounds part of the urethra, the canal that empties the bladder, and produces a fluid that forms part of semen. [NIH] Prostatic Hyperplasia: Enlargement or overgrowth of the prostate gland as a result of an increase in the number of its constituent cells. [NIH] Prosthesis: An artificial replacement of a part of the body. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protein Isoforms: Different forms of a protein that may be produced from different genes, or from the same gene by alternative splicing. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not working properly. [NIH] Proteoglycan: A molecule that contains both protein and glycosaminoglycans, which are a type of polysaccharide. Proteoglycans are found in cartilage and other connective tissues. [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] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Pseudotumor Cerebri: A condition marked by raised intracranial pressure and characterized clinically by headaches; nausea; papilledema, peripheral constriction of the

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visual fields, transient visual obscurations, and pulsatile tinnitus. Obesity is frequently associated with this condition, which primarily affects women between 20 and 44 years of age. Chronic papilledema may lead to optic nerve injury (optic nerve diseases) and visual loss (blindness). [NIH] Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] 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] Psychophysiology: The study of the physiological basis of human and animal behavior. [NIH]

Psychosis: A mental disorder characterized by gross impairment in reality testing as evidenced by delusions, hallucinations, markedly incoherent speech, or disorganized and agitated behaviour without apparent awareness on the part of the patient of the incomprehensibility of his behaviour; the term is also used in a more general sense to refer to mental disorders in which mental functioning is sufficiently impaired as to interfere grossly with the patient's capacity to meet the ordinary demands of life. Historically, the term has been applied to many conditions, e.g. manic-depressive psychosis, that were first described in psychotic patients, although many patients with the disorder are not judged psychotic. [EU] Psychosomatic: Pertaining to the mind-body relationship; having bodily symptoms of psychic, emotional, or mental origin; called also psychophysiologic. [EU] Psychotherapy: A generic term for the treatment of mental illness or emotional disturbances primarily by verbal or nonverbal communication. [NIH] Psychotomimetic: Psychosis miming. [NIH] Psychotropic: Exerting an effect upon the mind; capable of modifying mental activity; usually applied to drugs that effect the mental state. [EU] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]

Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH]

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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 Ventilation: The total volume of gas per minute inspired or expired measured in liters per minute. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]

Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Purpura: Purplish or brownish red discoloration, easily visible through the epidermis, caused by hemorrhage into the tissues. [NIH] Pyramidal Cells: Projection neurons in the cerebral cortex and the hippocampus. Pyramidal cells have a pyramid-shaped soma with the apex and an apical dendrite pointed toward the pial surface and other dendrites and an axon emerging from the base. The axons may have local collaterals but also project outside their cortical region. [NIH] Pyrexia: A fever, or a febrile condition; abnormal elevation of the body temperature. [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] Quiescent: Marked by a state of inactivity or repose. [EU] Quisqualic Acid: An agonist at two subsets of excitatory amino acid receptors, ionotropic receptors that directly control membrane channels and metabotropic receptors that indirectly mediate calcium mobilization from intracellular stores. The compound is obtained from the seeds and fruit of Quisqualis chinensis. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radioactive: Giving off radiation. [NIH] 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] Radioimmunotherapy: Radiotherapy where cytotoxic radionuclides are linked to antibodies in order to deliver toxins directly to tumor targets. Therapy with targeted radiation rather than antibody-targeted toxins (immunotoxins) has the advantage that adjacent tumor cells, which lack the appropriate antigenic determinants, can be destroyed by radiation cross-fire. Radioimmunotherapy is sometimes called targeted radiotherapy, but this latter term can

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also refer to radionuclides linked to non-immune molecules (radiotherapy). [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [NIH] Radiology: A specialty concerned with the use of x-ray and other forms of radiant energy in the diagnosis and treatment of disease. [NIH] Radiopharmaceutical: Any medicinal product which, when ready for use, contains one or more radionuclides (radioactive isotopes) included for a medicinal purpose. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] Raloxifene: A second generation selective estrogen receptor modulator (SERM) used to prevent osteoporosis in postmenopausal women. It has estrogen agonist effects on bone and cholesterol metabolism but behaves as a complete estrogen antagonist on mammary gland and uterine tissue. [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] Rape: Unlawful sexual intercourse without consent of the victim. [NIH] Reaction Time: The time from the onset of a stimulus until the organism responds. [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] Reality Testing: The individual's objective evaluation of the external world and the ability to differentiate adequately between it and the internal world; considered to be a primary ego function. [NIH] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Receptors, Serotonin: Cell-surface proteins that bind serotonin and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recovery of Function: A partial or complete return to the normal or proper physiologic activity of an organ or part following disease or trauma. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [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]

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Reflex: An involuntary movement or exercise of function in a part, excited in response to a stimulus applied to the periphery and transmitted to the brain or spinal cord. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Refractory: Not readily yielding to treatment. [EU] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Rehabilitative: Instruction of incapacitated individuals or of those affected with some mental disorder, so that some or all of their lost ability may be regained. [NIH] Reliability: Used technically, in a statistical sense, of consistency of a test with itself, i. e. the extent to which we can assume that it will yield the same result if repeated a second time. [NIH]

Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] 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 Design: A plan for collecting and utilizing data so that desired information can be obtained with sufficient precision or so that an hypothesis can be tested properly. [NIH] Resorption: The loss of substance through physiologic or pathologic means, such as loss of dentin and cementum of a tooth, or of the alveolar process of the mandible or maxilla. [EU] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Respiratory 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] Restitution: The restoration to a normal state. [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Resuscitation: The restoration to life or consciousness of one apparently dead; it includes such measures as artificial respiration and cardiac massage. [EU]

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Reticular: Coarse-fibered, netlike dermis layer. [NIH] Reticular Formation: A region extending from the pons & medulla oblongata through the mesencephalon, characterized by a diversity of neurons of various sizes and shapes, arranged in different aggregations and enmeshed in a complicated fiber network. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retinal Hemorrhage: Bleeding from the vessels of the retina. [NIH] Retinol: Vitamin A. It is essential for proper vision and healthy skin and mucous membranes. Retinol is being studied for cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Retinopathy: 1. Retinitis (= inflammation of the retina). 2. Retinosis (= degenerative, noninflammatory condition of the retina). [EU] Retrospective: Looking back at events that have already taken place. [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] Rhinorrhea: The free discharge of a thin nasal mucus. [EU] Ribonuclease: RNA-digesting enzyme. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Rod: A reception for vision, located in the retina. [NIH] 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] Saline: A solution of salt and water. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH]

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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] 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] Sciatic Nerve: A nerve which originates in the lumbar and sacral spinal cord (L4 to S3) and supplies motor and sensory innervation to the lower extremity. The sciatic nerve, which is the main continuation of the sacral plexus, is the largest nerve in the body. It has two major branches, the tibial nerve and the peroneal nerve. [NIH] Sclera: The tough white outer coat of the eyeball, covering approximately the posterior fivesixths of its surface, and continuous anteriorly with the cornea and posteriorly with the external sheath of the optic nerve. [EU] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Scopolamine: An alkaloid from Solanaceae, especially Datura metel L. and Scopola carniolica. Scopolamine and its quaternary derivatives act as antimuscarinics like atropine, but may have more central nervous system effects. Among the many uses are as an anesthetic premedication, in urinary incontinence, in motion sickness, as an antispasmodic, and as a mydriatic and cycloplegic. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Second Messenger Systems: Systems in which an intracellular signal is generated in response to an intercellular primary messenger such as a hormone or neurotransmitter. They are intermediate signals in cellular processes such as metabolism, secretion, contraction, phototransduction, and cell growth. Examples of second messenger systems are the adenyl cyclase-cyclic AMP system, the phosphatidylinositol diphosphate-inositol triphosphate system, and the cyclic GMP system. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH]

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Secretory Vesicles: Vesicles derived from the golgi apparatus containing material to be released at the cell surface. [NIH] Sedatives, Barbiturate: Those derivatives of barbituric or thiobarbituric acid that are used as hypnotics or sedatives. The structural class of all such derivatives, regardless of use, is barbiturates. [NIH] 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] Selective estrogen receptor modulator: SERM. A drug that acts like estrogen on some tissues, but blocks the effect of estrogen on other tissues. Tamoxifen and raloxifene are SERMs. [NIH] Self Care: Performance of activities or tasks traditionally performed by professional health care providers. The concept includes care of oneself or one's family and friends. [NIH] 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] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [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] Sepsis: The presence of bacteria in the bloodstream. [NIH] Septic: Produced by or due to decomposition by microorganisms; putrefactive. [EU] Septicemia: Systemic disease associated with the presence and persistence of pathogenic microorganisms or their toxins in the blood. Called also blood poisoning. [EU] Sequela: Any lesion or affection following or caused by an attack of disease. [EU] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serous: Having to do with serum, the clear liquid part of blood. [NIH] Sertraline: A selective serotonin uptake inhibitor that is used in the treatment of depression. [NIH]

Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral

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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]

Shoulder Pain: Unilateral or bilateral pain of the shoulder. It is often caused by physical activities such as work or sports participation, but may also be pathologic in origin. [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] Sigmoid: 1. Shaped like the letter S or the letter C. 2. The sigmoid colon. [EU] Sigmoid Colon: The lower part of the colon that empties into the rectum. [NIH] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] 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 many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skin Care: Maintenance of the hygienic state of the skin under optimal conditions of cleanliness and comfort. Effective in skin care are proper washing, bathing, cleansing, and the use of soaps, detergents, oils, etc. In various disease states, therapeutic and protective solutions and ointments are useful. The care of the skin is particularly important in various occupations, in exposure to sunlight, in neonates, and in decubitus ulcer. [NIH] Skin Tests: Epicutaneous or intradermal application of a sensitizer for demonstration of either delayed or immediate hypersensitivity. Used in diagnosis of hypersensitivity or as a test for cellular immunity. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Skull Fracture, Depressed: A skull fracture characterized by inward depression of a fragment or section of cranial bone, often compressing the underlying dura mater and brain. Depressed cranial fractures which feature open skin wounds that communicate with skull fragments are referred to as compound depressed skull fractures. [NIH] Skull Fractures: Fractures of the skull which may result from penetrating or nonpenetrating head injuries or rarely bone diseases (see also fractures, spontaneous). skull fractures may be classified by location (e.g., skull fracture, basilar), radiographic appearance (e.g., linear), or

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based upon cranial integrity (e.g., skull fracture, depressed). [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] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smoldering leukemia: Disease in which the bone marrow does not function normally. Also called preleukemia or myelodysplastic syndrome. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Soaps: Sodium or potassium salts of long chain fatty acids. These detergent substances are obtained by boiling natural oils or fats with caustic alkali. Sodium soaps are harder and are used as topical anti-infectives and vehicles in pills and liniments; potassium soaps are soft, used as vehicles for ointments and also as topical antimicrobials. [NIH] Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Social Support: Support systems that provide assistance and encouragement to individuals with physical or emotional disabilities in order that they may better cope. Informal social support is usually provided by friends, relatives, or peers, while formal assistance is provided by churches, groups, etc. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Sodium Channels: Cell membrane glycoproteins selective for sodium ions. Fast sodium current is associated with the action potential in neural membranes. [NIH] Sodium Iodide: Sodium iodide (NaI). A compound forming white, odorless deliquescent crystals and used as iodine supplement, expectorant or in its radioactive (I-131) form as an diagnostic aid, particularly for thyroid function determinants. [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] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Soma: The body as distinct from the mind; all the body tissue except the germ cells; all the axial body. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU]

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Sorbitol: A polyhydric alcohol with about half the sweetness of sucrose. Sorbitol occurs naturally and is also produced synthetically from glucose. It was formerly used as a diuretic and may still be used as a laxative and in irrigating solutions for some surgical procedures. It is also used in many manufacturing processes, as a pharmaceutical aid, and in several research applications. [NIH] Sound wave: An alteration of properties of an elastic medium, such as pressure, particle displacement, or density, that propagates through the medium, or a superposition of such alterations. [NIH] Spasm: An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. [NIH] Spastic: 1. Of the nature of or characterized by spasms. 2. Hypertonic, so that the muscles are stiff and the movements awkward. 3. A person exhibiting spasticity, such as occurs in spastic paralysis or in cerebral palsy. [EU] Spasticity: A state of hypertonicity, or increase over the normal tone of a muscle, with heightened deep tendon reflexes. [EU] Spatial disorientation: Loss of orientation in space where person does not know which way is up. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Speech Disorders: Acquired or developmental conditions marked by an impaired ability to comprehend or generate spoken forms of language. [NIH] Speech Intelligibility: Ability to make speech sounds that are recognizable. [NIH] Speech pathologist: A specialist who evaluates and treats people with communication and swallowing problems. Also called a speech therapist. [NIH] Speech-Language Pathology: The study of speech or language disorders and their diagnosis and correction. [NIH] Sperm: The fecundating fluid of the male. [NIH] Sphenoid: An unpaired cranial bone with a body containing the sphenoid sinus and forming the posterior part of the medial walls of the orbits. [NIH] Spina bifida: A defect in development of the vertebral column in which there is a central deficiency of the vertebral lamina. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spinal Cord Injuries: Penetrating and non-penetrating injuries to the spinal cord resulting from traumatic external forces (e.g., wounds, gunshot; whiplash injuries; etc.). [NIH]

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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] Spirochete: Lyme disease. [NIH] Spirometry: Measurement of volume of air inhaled or exhaled by the lung. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Sprains and Strains: A collective term for muscle and ligament injuries without dislocation or fracture. A sprain is a joint injury in which some of the fibers of a supporting ligament are ruptured but the continuity of the ligament remains intact. A strain is an overstretching or overexertion of some part of the musculature. [NIH] Sprue: A non febrile tropical disease of uncertain origin. [NIH] Squamous: Scaly, or platelike. [EU] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Squamous cells: Flat cells that look like fish scales under a microscope. These cells cover internal and external surfaces of the body. [NIH] Stabilization: The creation of a stable state. [EU] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH]

Status Epilepticus: Repeated and prolonged epileptic seizures without recovery of consciousness between attacks. [NIH] Steady state: Dynamic equilibrium. [EU] Steel: A tough, malleable, iron-based alloy containing up to, but no more than, two percent carbon and often other metals. It is used in medicine and dentistry in implants and instrumentation. [NIH] Stereotactic: Radiotherapy that treats brain tumors by using a special frame affixed directly to the patient's cranium. By aiming the X-ray source with respect to the rigid frame, technicians can position the beam extremely precisely during each treatment. [NIH] Sterile: Unable to produce children. [NIH] Sternum: Breast bone. [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]

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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] Streptococcal: Caused by infection due to any species of streptococcus. [NIH] Streptococcus: A genus of gram-positive, coccoid bacteria whose organisms occur in pairs or chains. No endospores are produced. Many species exist as commensals or parasites on man or animals with some being highly pathogenic. A few species are saprophytes and occur in the natural environment. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Striatum: A higher brain's domain thus called because of its stripes. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Stroke Volume: The amount of blood pumped out of the heart per beat not to be confused with cardiac output (volume/time). [NIH] Stroma: The middle, thickest layer of tissue in the cornea. [NIH] Stromal: Large, veil-like cell in the bone marrow. [NIH] Stromal Cells: Connective tissue cells of an organ found in the loose connective tissue. These are most often associated with the uterine mucosa and the ovary as well as the hematopoietic system and elsewhere. [NIH] Stupor: Partial or nearly complete unconsciousness, manifested by the subject's responding only to vigorous stimulation. Also, in psychiatry, a disorder marked by reduced responsiveness. [EU] Subacute: Somewhat acute; between acute and chronic. [EU] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Subiculum: A region of the hippocampus that projects to other areas of the brain. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]

Substrate: A substance upon which an enzyme acts. [EU] Sunburn: An injury to the skin causing erythema, tenderness, and sometimes blistering and resulting from excessive exposure to the sun. The reaction is produced by the ultraviolet radiation in sunlight. [NIH] Superoxide: Derivative of molecular oxygen that can damage cells. [NIH]

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Superoxide Dismutase: An oxidoreductase that catalyzes the reaction between superoxide anions and hydrogen to yield molecular oxygen and hydrogen peroxide. The enzyme protects the cell against dangerous levels of superoxide. EC 1.15.1.1. [NIH] Supplementation: Adding nutrients to the diet. [NIH] 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] Survival Rate: The proportion of survivors in a group, e.g., of patients, studied and followed over a period, or the proportion of persons in a specified group alive at the beginning of a time interval who survive to the end of the interval. It is often studied using life table methods. [NIH] Sympathetic Nervous System: The thoracolumbar division of the autonomic nervous system. Sympathetic preganglionic fibers originate in neurons of the intermediolateral column of the spinal cord and project to the paravertebral and prevertebral ganglia, which in turn project to target organs. The sympathetic nervous system mediates the body's response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system. [NIH] Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Symptomatic treatment: Therapy that eases symptoms without addressing the cause of disease. [NIH] Symptomatology: 1. That branch of medicine with treats of symptoms; the systematic discussion of symptoms. 2. The combined symptoms of a disease. [EU] Synapses: Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate through direct electrical connections which are sometimes called electrical synapses; these are not included here but rather in gap junctions. [NIH] Synapsis: The pairing between homologous chromosomes of maternal and paternal origin during the prophase of meiosis, leading to the formation of gametes. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synaptic Transmission: The communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. In chemical synaptic transmission, the presynaptic neuron releases a neurotransmitter that diffuses across the synaptic cleft and binds to specific synaptic receptors. These activated receptors modulate ion channels and/or secondmessenger systems to influence the postsynaptic cell. Electrical transmission is less common in the nervous system, and, as in other tissues, is mediated by gap junctions. [NIH]

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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] 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] Synovial: Of pertaining to, or secreting synovia. [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] Tamoxifen: A first generation selective estrogen receptor modulator (SERM). It acts as an agonist for bone tissue and cholesterol metabolism but is an estrogen antagonist in mammary and uterine. [NIH] Tau Proteins: One of the two major classes of microtubule-associated proteins isolated from the brain. The proteins have two domains: one that binds to microtubules and a second that binds to other cell components. By binding to several unpolymerized tubulin molecules simultaneously, tau proteins speed up the nucleation process in tubulin polymerization. Chemically modified tau proteins also appear to be involved in the formation and/or composition of the neurofibrillary tangles and neuropil threads found in Alzheimer disease. [NIH]

Taurine: 2-Aminoethanesulfonic acid. A conditionally essential nutrient, important during mammalian development. It is present in milk but is isolated mostly from ox bile and strongly conjugates bile acids. [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] Tetrahydrocannabinol: A psychoactive compound extracted from the resin of Cannabis sativa (marihuana, hashish). The isomer delta-9-tetrahydrocannabinol (THC) is considered the most active form, producing characteristic mood and perceptual changes associated with this compound. Dronabinol is a synthetic form of delta-9-THC. [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

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diencephalon and is commonly divided into cellular aggregates known as nuclear groups. [NIH]

Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Third Ventricle: A narrow cleft inferior to the corpus callosum, within the diencephalon, between the paired thalami. Its floor is formed by the hypothalamus, its anterior wall by the lamina terminalis, and its roof by ependyma. It communicates with the fourth ventricle by the cerebral aqueduct, and with the lateral ventricles by the interventricular foramina. [NIH] Thoracic: Having to do with the chest. [NIH] Thoracic Surgery: A surgical specialty concerned with diagnosis and treatment of disorders of the heart, lungs, and esophagus. Two major types of thoracic surgery are classified as pulmonary and cardiovascular. [NIH] Thorax: A part of the trunk between the neck and the abdomen; the chest. [NIH] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombocytes: Blood cells that help prevent bleeding by causing blood clots to form. Also called platelets. [NIH] Thromboembolism: Obstruction of a vessel by a blood clot that has been transported from a distant site by the blood stream. [NIH] Thrombolytic: 1. Dissolving or splitting up a thrombus. 2. A thrombolytic agent. [EU] Thrombolytic Therapy: Use of infusions of fibrinolytic agents to destroy or dissolve thrombi in blood vessels or bypass grafts. [NIH] Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thromboxanes: Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators of the actions of polyunsaturated fatty acids transformed by cyclooxygenase. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Thyrotropin: A peptide hormone secreted by the anterior pituitary. It promotes the growth of the thyroid gland and stimulates the synthesis of thyroid hormones and the release of thyroxine by the thyroid gland. [NIH]

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Tibial Nerve: The medial terminal branch of the sciatic nerve. The tibial nerve fibers originate in lumbar and sacral spinal segments (L4 to S2). They supply motor and sensory innervation to parts of the calf and foot. [NIH] Tic: An involuntary compulsive, repetitive, stereotyped movement, resembling a purposeful movement because it is coordinated and involves muscles in their normal synergistic relationships; tics usually involve the face and shoulders. [EU] Tidal Volume: The volume of air inspired or expired during each normal, quiet respiratory cycle. Common abbreviations are TV or V with subscript T. [NIH] Tinnitus: Sounds that are perceived in the absence of any external noise source which may take the form of buzzing, ringing, clicking, pulsations, and other noises. Objective tinnitus refers to noises generated from within the ear or adjacent structures that can be heard by other individuals. The term subjective tinnitus is used when the sound is audible only to the affected individual. Tinnitus may occur as a manifestation of cochlear diseases; vestibulocochlear nerve diseases; intracranial hypertension; craniocerebral trauma; and other conditions. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] Topical: On the surface of the body. [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] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Traction: The act of pulling. [NIH] Trail Making Test: The subject's ability to connect 25 numbered and lettered circles in sequence in a specific length of time. A score of 12 or below is suggestive of organic brain damage. [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle

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(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] Transient Ischemic Attacks: Focal neurologic abnormalities of sudden onset and brief duration that reflect dysfunction in the distribution of the internal carotid-middle cerebral or the vertebrobasilar arterial system. [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] Translocation: The movement of material in solution inside the body of the plant. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] 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] Trauma Centers: Specialized hospital facilities which provide diagnostic and therapeutic services for trauma patients. [NIH] Trees: Woody, usually tall, perennial higher plants (Angiosperms, Gymnosperms, and some Pterophyta) having usually a main stem and numerous branches. [NIH] Tremor: Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of cerebellar diseases, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of Parkinson disease. [NIH] Trigeminal: Cranial nerve V. It is sensory for the eyeball, the conjunctiva, the eyebrow, the skin of face and scalp, the teeth, the mucous membranes in the mouth and nose, and is motor to the muscles of mastication. [NIH] Trisomy: The possession of a third chromosome of any one type in an otherwise diploid cell. [NIH]

Trophic: Of or pertaining to nutrition. [EU] 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] Tuberculin: A sterile liquid containing the growth products of, or specific substances extracted from, the tubercle bacillus; used in various forms in the diagnosis of tuberculosis. [NIH]

Tuberculin Test: One of several skin tests to determine past or present tuberculosis infection. A purified protein derivative of the tubercle bacilli, called tuberculin, is introduced into the skin by scratch, puncture, or interdermal injection. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of

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Mycobacterium. [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 Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] Type 2 diabetes: Usually characterized by a gradual onset with minimal or no symptoms of metabolic disturbance and no requirement for exogenous insulin. The peak age of onset is 50 to 60 years. Obesity and possibly a genetic factor are usually present. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Ulcerative colitis: Chronic inflammation of the colon that produces ulcers in its lining. This condition is marked by abdominal pain, cramps, and loose discharges of pus, blood, and mucus from the bowel. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Uraemia: 1. An excess in the blood of urea, creatinine, and other nitrogenous end products of protein and amino acids metabolism; more correctly referred to as azotemia. 2. In current usage the entire constellation of signs and symptoms of chronic renal failure, including nausea, vomiting anorexia, a metallic taste in the mouth, a uraemic odour of the breath, pruritus, uraemic frost on the skin, neuromuscular disorders, pain and twitching in the muscles, hypertension, edema, mental confusion, and acid-base and electrolyte imbalances. [EU]

Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary tract: The organs of the body that produce and discharge urine. These include the kidneys, ureters, bladder, and urethra. [NIH] Urinary tract infection: An illness caused by harmful bacteria growing in the urinary tract. [NIH]

Urinate: To release urine from the bladder to the outside. [NIH] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] 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] Uvea: The middle coat of the eyeball, consisting of the choroid in the back of the eye and the ciliary body and iris in the front of the eye. [NIH] Uveitis: An inflammation of part or all of the uvea, the middle (vascular) tunic of the eye, and commonly involving the other tunics (the sclera and cornea, and the retina). [EU] 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]

372


Vagal: Pertaining to the vagus nerve. [EU] 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] Valves: Flap-like structures that control the direction of blood flow through the heart. [NIH] Vanadium: Vanadium. A metallic element with the atomic symbol V, atomic number 23, and atomic weight 50.94. It is used in the manufacture of vanadium steel. Prolonged exposure can lead to chronic intoxication caused by absorption usually via the lungs. [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 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] Vasculitis: Inflammation of a blood vessel. [NIH] Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [NIH] Vasodilatation: A state of increased calibre of the blood vessels. [EU] Vasodilator: An agent that widens blood vessels. [NIH] Vasomotor: 1. Affecting the calibre of a vessel, especially of a blood vessel. 2. Any element or agent that effects the calibre of a blood vessel. [EU] Vasopressor: 1. Stimulating contraction of the muscular tissue of the capillaries and arteries. 2. An agent that stimulates contraction of the muscular tissue of the capillaries and arteries. [EU]

Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vegetative: 1. Concerned with growth and with nutrition. 2. Functioning involuntarily or unconsciously, as the vegetative nervous system. 3. Resting; denoting the portion of a cell cycle during which the cell is not involved in replication. 4. Of, pertaining to, or characteristic of plants. [EU] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venereal: Pertaining or related to or transmitted by sexual contact. [EU] Venous: Of or pertaining to the veins. [EU] Venous blood: Blood that has given up its oxygen to the tissues and carries carbon dioxide back for gas exchange. [NIH] Ventilation: 1. In respiratory physiology, the process of exchange of air between the lungs and the ambient air. Pulmonary ventilation (usually measured in litres per minute) refers to the total exchange, whereas alveolar ventilation refers to the effective ventilation of the alveoli, in which gas exchange with the blood takes place. 2. In psychiatry, verbalization of one's emotional problems. [EU] Ventral: 1. Pertaining to the belly or to any venter. 2. Denoting a position more toward the 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

Dictionary 373

body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vertebrae: A bony unit of the segmented spinal column. [NIH] Vertebral: Of or pertaining to a vertebra. [EU] Vertigo: An illusion of movement; a sensation as if the external world were revolving around the patient (objective vertigo) or as if he himself were revolving in space (subjective vertigo). The term is sometimes erroneously used to mean any form of dizziness. [EU] Vestibulocochlear Nerve: The 8th cranial nerve. The vestibulocochlear nerve has a cochlear part (cochlear nerve) which is concerned with hearing and a vestibular part (vestibular nerve) which mediates the sense of balance and head position. The fibers of the cochlear nerve originate from neurons of the spiral ganglion and project to the cochlear nuclei (cochlear nucleus). The fibers of the vestibular nerve arise from neurons of Scarpa's ganglion and project to the vestibular nuclei. [NIH] Vestibulocochlear Nerve Diseases: Diseases of the vestibular and/or cochlear (acoustic) nerves, which join to form the vestibulocochlear nerve. Vestibular neuritis, cochlear neuritis, and acoustic neuromas are relatively common conditions that affect these nerves. Clinical manifestations vary with which nerve is primarily affected, and include hearing loss, vertigo, and tinnitus. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral vector: A type of virus used in cancer therapy. The virus is changed in the laboratory and cannot cause disease. Viral vectors produce tumor antigens (proteins found on a tumor cell) and can stimulate an antitumor immune response in the body. Viral vectors may also be used to carry genes that can change cancer cells back to normal cells. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Viscera: Any of the large interior organs in any one of the three great cavities of the body, especially in the abdomen. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Visceral Afferents: The sensory fibers innervating the viscera. [NIH] Viscosity: A physical property of fluids that determines the internal resistance to shear forces. [EU] 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] Voice Quality: Voice quality is that component of speech which gives the primary

374


distinction to a given speaker's voice when pitch and loudness are excluded. It involves both phonatory and resonatory characteristics. Some of the descriptions of voice quality are harshness, breathiness and nasality. [NIH] Void: To urinate, empty the bladder. [NIH] Wakefulness: A state in which there is an enhanced potential for sensitivity and an efficient responsiveness to external stimuli. [NIH] War: Hostile conflict between organized groups of people. [NIH] Weight Gain: Increase in body weight over existing weight. [NIH] Wheelchairs: Chairs mounted on wheels and designed to be propelled by the occupant. [NIH]

White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]

Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Wounds, Gunshot: Disruption of structural continuity of the body as a result of the discharge of firearms. [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]

375

INDEX 1 1-Propanol, 181, 285 A Abdomen, 153, 285, 295, 296, 300, 328, 330, 331, 365, 368, 372, 373 Abdominal, 153, 285, 309, 328, 345, 347, 371 Abdominal Pain, 285, 328, 347, 371 Aberrant, 59, 155, 285 Acceptor, 285, 331, 344 Acetylcholine, 36, 285, 300, 301, 342 Acetylcysteine, 117, 121, 285 Acidosis, 39, 63, 285 Acoustic, 6, 36, 46, 136, 285, 373 Action Potentials, 149, 184, 285 Activities of Daily Living, 40, 285 Acute Disease, 18, 285 Acute myelogenous leukemia, 184, 285 Acute myeloid leukemia, 285 Acute nonlymphocytic leukemia, 285 Adaptability, 285, 299 Adaptation, 14, 285, 349 Adenine, 286, 355 Adenosine, 8, 286, 348 Adhesives, 149, 286 Adjustment, 15, 37, 60, 96, 113, 193, 285, 286 Adrenal Cortex, 286, 306, 323, 352 Adrenal Glands, 286 Adrenal insufficiency, 34, 286 Adrenal Medulla, 155, 286, 299, 301, 314, 342, 345 Adrenergic, 116, 286, 290, 310, 314, 366 Adverse Effect, 78, 162, 286, 361 Aerobic, 286, 336, 344 Aerobic Metabolism, 286, 344 Aerobic Respiration, 286, 344 Afferent, 146, 166, 286, 351 Affinity, 104, 170, 171, 286, 287, 292, 340, 362 Age of Onset, 287, 371 Airway, 7, 87, 164, 287, 297, 353, 362 Airway Resistance, 7, 287 Alertness, 148, 287 Alexia, 287, 311 Algorithms, 287, 295 Alimentary, 287, 346 Alkaline, 285, 287, 288, 297, 345

Alkaloid, 287, 292, 296, 302, 342, 359 Alleles, 22, 287 Allergen, 287, 360 Allergic Rhinitis, 168, 287 Allylamine, 287, 288 Alpha Particles, 287, 355 Alternative medicine, 125, 133, 214, 287 Alternative Splicing, 152, 287, 353 Aluminum, 161, 287 Alveolar Process, 287, 357 Amantadine, 43, 66, 288 Amenorrhea, 288, 296, 350 Amine, 178, 288 Amino Acid Sequence, 288, 290, 315, 319 Amino Acids, 145, 288, 292, 315, 319, 341, 346, 350, 353, 358, 360, 370, 371 Ammonia, 288 Amnesia, 17, 54, 128, 151, 288 Amnestic, 288, 334 Amphetamine, 20, 288, 308 Amputation, 24, 49, 288 Amygdala, 160, 288, 293, 331, 367 Amyloid, 55, 66, 288 Amyloid beta-Protein, 66, 288 Anaesthesia, 120, 288, 325 Anal, 289, 317, 332 Analgesics, 251, 283, 289 Analogous, 38, 289, 370 Anaphylatoxins, 289, 303 Anatomical, 19, 35, 46, 157, 289, 292, 305, 312, 325, 340, 345, 359 Anemia, 289, 295, 333, 337 Anesthesia, 31, 83, 84, 85, 86, 87, 88, 89, 91, 287, 289, 329, 340 Anesthetics, 289, 293, 314 Aneurism, 179, 289 Angina, 25, 149, 183, 289 Angina Pectoris, 149, 183, 289 Angiogenesis, 11, 289, 334 Animal model, 20, 23, 25, 29, 41, 44, 168, 289 Anions, 289, 328, 366 Ankle, 248, 253, 261, 289 Anorexia, 144, 166, 289, 371 Anovulation, 289, 350 Anoxia, 151, 231, 289 Anterior Cerebral Artery, 289, 300 Antibacterial, 290, 363

376

Traumatic brain injury

Antibiotic, 164, 290, 306, 351, 363 Antibodies, 61, 290, 321, 323, 325, 332, 349, 355 Antibody, 286, 290, 303, 321, 322, 325, 326, 334, 355, 356, 360, 363 Anticonvulsants, 290, 293 Antidepressant, 17, 290 Antigen, 286, 290, 303, 322, 324, 325, 326, 334, 360 Antigen-Antibody Complex, 290, 303 Anti-infective, 290, 323, 328, 362 Anti-inflammatory, 29, 144, 166, 290, 319 Antimicrobial, 249, 290, 308 Antioxidant, 50, 116, 117, 121, 157, 290, 342, 344 Antipsychotic, 290, 340 Antispasmodic, 291, 359 Antiviral, 285, 288, 291, 327 Anxiety, 34, 36, 99, 129, 146, 147, 149, 166, 168, 169, 182, 183, 188, 189, 291, 351 Anxiety Disorders, 147, 291 Anxiolytic, 145, 181, 291 Aorta, 160, 291, 298, 373 Apathy, 43, 159, 291, 340 Aperture, 167, 291 Aphasia, 151, 234, 235, 288, 291 Apnea, 159, 248, 291 Apoptosis, 10, 27, 39, 63, 139, 151, 184, 291, 298 Applicability, 161, 291 Apraxia, 235, 291 Aqueous, 291, 294, 307, 312, 323, 330 Arachidonate 12-Lipoxygenase, 291, 331 Arachidonate 15-Lipoxygenase, 291, 331 Arachidonate Lipoxygenases, 291, 331 Arachidonic Acid, 164, 291, 311, 330, 331, 342, 352, 353 Arginine, 27, 119, 289, 291, 342 Arrhythmia, 149, 183, 292 Arterial, 20, 41, 287, 292, 296, 300, 305, 323, 324, 353, 367, 370 Arteries, 27, 291, 292, 295, 300, 305, 329, 335, 338, 368, 372 Arterioles, 292, 295, 335, 338, 372 Arteriovenous, 18, 95, 292, 335 Articular, 292, 344 Articulation, 207, 292, 311, 335 Aspartate, 46, 55, 146, 166, 182, 183, 292, 329, 348 Aspartic, 145, 181, 292, 315 Aspartic Acid, 145, 181, 292 Astrocytes, 29, 53, 59, 292, 319, 336, 340

Asymptomatic, 292, 345 Ataxia, 244, 292, 323, 325, 367 Atopic, 184, 292 Atrial, 243, 248, 267, 292, 305 Atrial Fibrillation, 243, 248, 267, 292 Atrium, 292, 298, 305, 372 Atrophy, 70, 176, 186, 292, 340 Atropine, 292, 359 Attenuated, 292, 309 Attenuation, 28, 47, 116, 121, 177, 292 Atypical, 109, 292 Audition, 98, 293 Auditory, 6, 15, 36, 71, 125, 126, 192, 293, 315, 321, 334, 351, 372 Autodigestion, 293, 345 Autoimmune disease, 184, 293, 337 Autoimmunity, 69, 150, 293 Autonomic, 31, 71, 161, 285, 290, 293, 342, 347, 362, 366 Autonomic Nervous System, 293, 347, 362, 366 Autopsy, 9, 34, 65, 293 Autoradiography, 41, 293 Axonal, 11, 12, 68, 76, 104, 156, 168, 175, 179, 187, 293 Axons, 168, 175, 179, 293, 308, 309, 339, 341, 344, 347, 355 B Bacillus, 293, 370 Back Pain, 239, 246, 293 Bacteria, 144, 166, 290, 293, 308, 312, 313, 316, 335, 336, 356, 360, 363, 365, 369, 371 Bacterial Physiology, 286, 293 Bactericidal, 293, 314 Bacteriophage, 293, 349, 369 Barbiturates, 8, 68, 84, 293, 360 Basal Ganglia, 290, 292, 293, 296, 301, 311, 331 Basal Ganglia Diseases, 292, 293, 301, 311 Base, 17, 161, 286, 294, 308, 319, 329, 355, 367, 371 Basement Membrane, 294, 315, 329 Basophil, 184, 294 Bed Rest, 212, 294 Benign, 156, 157, 168, 176, 294, 321, 339, 356 Benign prostatic hyperplasia, 168, 294 Beta-pleated, 288, 294 Bewilderment, 294, 304 Bifida, 49, 294 Bilateral, 23, 26, 27, 294, 346, 350, 361 Bile, 294, 318, 331, 364, 367

377

Bile Acids, 294, 364, 367 Biliary, 294, 345 Biliary Tract, 294, 345 Binding Sites, 29, 145, 294 Bioavailability, 184, 294 Biochemical, 10, 12, 15, 24, 29, 35, 37, 62, 63, 69, 117, 287, 294, 319, 344, 360 Biological response modifier, 294, 327 Biological therapy, 294, 320 Biological Transport, 294, 309 Biomechanics, 32, 294 Biopsy, 294, 346 Biosynthesis, 29, 291, 294, 353, 360 Biotechnology, 64, 65, 214, 225, 295 Biphasic, 157, 295 Bipolar Disorder, 163, 169, 173, 295 Bladder, 148, 149, 153, 177, 183, 294, 295, 301, 318, 325, 337, 340, 353, 371, 374 Blast phase, 295, 301 Bloating, 295, 328 Blood Coagulation, 295, 297 Blood Glucose, 250, 295, 322, 327 Blood Platelets, 164, 295, 360 Blood pressure, 9, 20, 34, 60, 69, 87, 188, 270, 295, 298, 324, 336, 342, 362 Blood transfusion, 295, 322 Blood Viscosity, 185, 295, 322 Blood Volume, 52, 158, 162, 295 Blood-Brain Barrier, 29, 295 Body Fluids, 295, 297, 317, 343, 362 Bolus, 52, 295 Bolus infusion, 295 Bone Marrow, 11, 61, 285, 295, 301, 325, 332, 337, 338, 351, 362, 365 Bone metastases, 296 Bone Resorption, 184, 296 Bone scan, 296, 359 Boron, 296, 306 Bowel, 149, 150, 163, 168, 169, 170, 183, 184, 289, 296, 305, 326, 328, 347, 365, 371 Bowel Movement, 296, 305, 365 Bradykinin, 296, 342 Brain Diseases, 150, 230, 296, 330 Brain Hypoxia, 296, 367 Brain Infarction, 296 Brain Ischemia, 177, 296, 324 Brain Stem, 154, 296, 300, 340 Branch, 118, 119, 120, 279, 296, 312, 334, 341, 346, 354, 363, 366, 368, 369 Breakdown, 296, 299, 309, 318, 343 Bromocriptine, 71, 116, 296 Bronchi, 296, 297, 314, 315, 369

Bronchial, 168, 297 Bronchial Hyperreactivity, 168, 297 Bronchitis, 297, 301 Buccal, 297, 332 Bulbar, 175, 297 Bypass, 297, 338, 368 C Cachexia, 150, 297 Calcium, 19, 39, 46, 50, 62, 63, 139, 145, 152, 172, 182, 183 Calcium Channels, 62, 63, 152, 172, 297 Calmodulin, 63, 297 Calpain, 50, 297 Cannabidiol, 297 Cannabinoids, 144, 165, 297 Cannabinol, 297 Carbohydrate, 297, 319, 350 Carbon Dioxide, 297, 317, 318, 323, 324, 349, 357, 372 Carbon Monoxide Poisoning, 157, 298 Carboxy, 150, 298, 329 Carboxy-terminal, 150, 298 Carcinogenic, 298, 326, 364 Carcinoma, 238, 242, 243, 298 Cardiac arrest, 152, 153, 185, 298 Cardiac Output, 153, 185, 298, 365 Cardiopulmonary, 152, 153, 161, 298, 322 Cardiopulmonary Bypass, 298, 322 Cardiopulmonary Resuscitation, 153, 298 Cardiorespiratory, 105, 298 Cardiovascular disease, 163, 169, 173, 250, 298 Cardiovascular System, 145, 181, 298 Carnitine, 156, 298 Carotene, 298, 358 Case report, 4, 34, 298, 302 Caspase, 11, 12, 13, 21, 39, 298 Cataract, 163, 298, 314 Catecholamine, 299, 310, 347 Catheterization, 299, 328, 338 Cations, 299, 328 Caudal, 299, 309, 324, 350 Causal, 26, 299 Cause of Death, 21, 42, 52, 174, 189, 299 Cell Cycle, 299, 372 Cell Differentiation, 299, 361 Cell Division, 293, 299, 320, 334, 336, 349, 352 Cell membrane, 149, 184, 294, 297, 299, 308, 318, 329, 348, 350, 362 Cell proliferation, 299, 361 Cell Respiration, 286, 299, 336, 344, 357

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Cell Survival, 42, 179, 299, 320 Cellular metabolism, 116, 299 Central Nervous System Infections, 299, 321, 323 Cerebellar, 25, 36, 137, 161, 292, 300, 356, 370 Cerebellum, 160, 296, 300, 318, 350, 356 Cerebral Arteries, 300, 336 Cerebral hemispheres, 293, 296, 300 Cerebral Infarction, 25, 296, 300, 323 Cerebral Palsy, 49, 151, 186, 230, 300, 363 Cerebrospinal, 9, 24, 56, 62, 66, 71, 80, 81, 83, 93, 104, 116, 127, 159, 185, 300, 323 Cerebrospinal fluid, 9, 24, 56, 62, 66, 71, 80, 81, 83, 93, 104, 116, 127, 159, 300, 323 Cerebrovascular, 25, 28, 57, 71, 121, 158, 162, 171, 186, 244, 293, 298, 300, 342, 367 Cerebrum, 24, 300 Cervical, 77, 161, 246, 252, 300, 339 Cervix, 300, 317 Character, 25, 289, 300, 307 Chelation, 129, 300 Chemotactic Factors, 300, 303, 342 Chemotherapy, 158, 238, 250, 300 Chest Pain, 253, 300 Chest wall, 153, 300 Cholesterol, 294, 300, 305, 356, 364, 367 Choline, 42, 300 Cholinergic, 15, 36, 122, 189, 290, 300, 301, 342 Cholinesterase Inhibitors, 45, 159, 180, 301, 310 Chorea, 188, 290, 301 Choreatic Disorders, 301 Chromaffin Cells, 155, 301, 345 Chromatin, 291, 301 Chromic, 301 Chromosome, 32, 288, 301, 331, 370 Chronic Disease, 297, 301, 303 Chronic lymphocytic leukemia, 301 Chronic myelogenous leukemia, 295, 301 Chronic Obstructive Pulmonary Disease, 149, 170, 183, 240, 301 Chronic phase, 34, 301 Chronic renal, 301, 350, 371 Circadian, 188, 301 Circadian Rhythm, 188, 301 Circulatory system, 169, 302, 313, 328 CIS, 302, 358 Clamp, 35, 302 Claudication, 149, 183, 302 Clinical Medicine, 9, 302, 351

Clinical study, 302, 305 Clinical trial, 8, 14, 16, 24, 27, 28, 33, 43, 47, 53, 168, 225 Cloning, 295, 302 Coagulation, 94, 295, 302, 322, 368 Coca, 302 Cocaine, 171, 302 Cochlear, 302, 369, 373 Cochlear Diseases, 302, 369 Coenzyme, 156, 157, 302 Cofactor, 302, 353 Cognition, 7, 22, 36, 40, 43, 95, 98, 156, 188, 189, 195, 198, 205, 302, 329, 340 Cognition Disorders, 156, 302 Cognitive restructuring, 7, 303 Colitis, 184, 303, 328 Collagen, 164, 286, 294, 303, 316, 317, 318, 323, 334, 349, 352 Collagen disease, 303, 323 Collapse, 296, 303, 362 Colloidal, 303, 315 Comatose, 125, 282, 303 Combination Therapy, 117, 303 Communication Disorders, 6, 7, 194, 195, 199, 205, 209, 224, 232, 234, 236, 303 Complement, 9, 62, 289, 303, 304, 360 Complementary and alternative medicine, 125, 133, 303 Complementary medicine, 125, 304 Computational Biology, 225, 304 Computed tomography, 76, 268, 304, 359 Computerized axial tomography, 304, 359 Computerized tomography, 304 Concomitant, 11, 304, 339 Conduction, 178, 304, 340 Cones, 304, 358 Confusion, 66, 282, 304, 310, 324, 340, 371 Congestive heart failure, 184, 304 Conjugated, 304, 307 Conjunctiva, 304, 326, 370 Connective Tissue, 296, 303, 304, 317, 318, 332, 347, 353, 358, 365 Consolidation, 111, 160, 304 Constipation, 267, 290, 304, 328, 347 Constitutional, 304, 338 Constriction, 171, 304, 305, 328, 353, 372 Constriction, Pathologic, 305, 372 Consultation, 5, 108, 305 Consumption, 116, 117, 305, 345 Continence, 268, 305 Continuum, 22, 35, 148, 305 Contraindications, ii, 305

379

Contralateral, 305, 335, 343, 356 Controlled clinical trial, 43, 54, 90, 118, 128, 305 Contusion, 15, 21, 24, 27, 44, 121, 129, 130, 156, 175, 305 Convulsions, 149, 183, 282, 305, 317, 324, 341 Coordination, 29, 127, 236, 300, 305, 337 Cor, 305 Cornea, 305, 359, 365, 371 Coronary, 149, 158, 183, 271, 289, 298, 305, 306, 335, 338 Coronary Circulation, 289, 305 Coronary heart disease, 271, 298, 305 Coronary Thrombosis, 306, 335, 338 Corpus, 306, 346, 352, 368 Corpus Luteum, 306, 352 Cortex, 9, 19, 20, 44, 56, 58, 121, 291, 292, 296, 300, 306, 313, 315, 316, 317, 336, 339, 351, 355, 356 Cortical, 10, 12, 15, 20, 21, 23, 24, 26, 27, 37, 44, 56, 116, 121 Corticosteroids, 85, 117, 306, 319 Cortisol, 9, 34, 306 Cranial, 156, 300, 306, 321, 328, 339, 343, 345, 347, 361, 362, 363, 370, 372, 373 Craniocerebral Trauma, 293, 306, 321, 323, 367, 369 Craniotomy, 25, 77, 306 Creatine, 126, 156, 157, 212, 306 Creatinine, 306, 371 Critical Care, 8, 34, 116, 122, 251 Critical Illness, 9, 306 Cues, 151, 306 Curative, 306, 368 Curcumin, 176, 306 Cutaneous, 306, 323, 332 Cyanide, 178, 306 Cyclic, 164, 170, 297, 306, 320, 342, 348, 352, 359 Cycloserine, 187, 306 Cysteine, 117, 121, 150, 285, 297, 306, 307 Cystine, 306 Cytochrome, 13, 39, 307 Cytokine, 9, 32, 144, 151, 166, 175, 176, 307 Cytoplasm, 291, 299, 307, 313, 320, 337, 338, 340, 358, 367 Cytoskeletal Proteins, 297, 307 Cytotoxic, 43, 177, 307, 355, 356, 361 D Data Collection, 50, 307, 317 Databases, Bibliographic, 225, 307

Decubitus, 307, 361 Decubitus Ulcer, 307, 361 Defibrillation, 153, 307 Degenerative, 19, 45, 145, 155, 156, 157, 177, 181, 184, 188, 189 Deletion, 291, 307 Delirium, 97, 110, 159, 290, 307 Delivery of Health Care, 308, 321 Delusions, 308, 354 Demyelinating Diseases, 177, 308 Dendrites, 46, 308, 341, 355 Dendritic, 11, 46, 308, 334 Dental Caries, 269, 308 Dental Hygienists, 3, 308 Dentate Gyrus, 11, 64, 308, 322 Depolarization, 152, 172, 178, 308, 361 Depressive Disorder, 240, 308 Deprivation, 12, 57, 308 Dermatitis, 184, 308 Detergents, 308, 361 Deuterium, 308, 323 Dextroamphetamine, 288, 308, 335 Diabetes Mellitus, 157, 238, 250, 260, 309, 319, 322 Diabetic Retinopathy, 164, 309, 348 Diagnostic Imaging, 61, 309 Diagnostic procedure, 92, 143, 214, 309 Diagnostic Services, 309, 367 Diaphragm, 153, 309 Diarrhea, 309, 328 Diarrhoea, 149, 183, 309 Diastolic, 309, 324 Diastolic blood pressure, 309, 324 Diencephalon, 309, 324, 340, 351, 368 Diffuse Axonal Injury, 66, 168, 175, 296, 309 Diffusion, 43, 93, 294, 309 Digestion, 287, 294, 296, 309, 328, 331, 365 Digestive tract, 309, 362, 364 Dihydroxy, 163, 164, 309 Dilatation, 289, 309, 351 Dilution, 68, 309, 314, 349 Dimethyl, 178, 188, 219, 309 Disinfectant, 310, 314 Dislocation, 186, 310, 364 Disorientation, 304, 307, 310 Dissociation, 286, 310, 328 Distal, 178, 293, 310, 311, 341, 353 Diuretic, 310, 333, 363 Dizziness, 55, 157, 192, 310, 373 Domestic Violence, 77, 310, 350 Donepezil, 45, 67, 117, 159, 180, 310

380


Dopamine, 31, 118, 155, 171, 288, 290, 296, 302, 309, 310, 336, 348 Dorsal, 161, 310, 350, 364 Dorsum, 310 Drive, ii, vi, 41, 47, 115, 310 Drug Interactions, 218, 310 Drug Tolerance, 310, 369 Duodenum, 169, 294, 311, 329, 365 Dura mater, 311, 334, 345, 361 Dyes, 288, 311 Dysarthria, 6, 36, 94, 95, 235, 311 Dyskinesias, 293, 311, 337 Dyslexia, 159, 311 Dysmenorrhea, 149, 183, 311 Dysphagia, 72, 93, 118, 244, 247, 311 Dysphoric, 308, 311 E Edema, 24, 27, 52, 53, 132, 144, 158, 159, 162, 165, 168 Effector, 12, 160, 285, 303, 311, 341, 348 Effector cell, 311, 341 Efficacy, 4, 6, 12, 14, 16, 24, 25, 27, 28, 37, 45, 51, 52, 53, 59, 116, 119, 138, 155, 168 Eicosanoids, 28, 311 Elastin, 303, 311, 316 Elective, 106, 188, 189, 311 Electric shock, 298, 307, 311 Electrocardiography, 267, 311 Electrocoagulation, 302, 311 Electrode, 153, 154, 186, 311 Electrolyte, 308, 311, 317, 343, 350, 362, 371 Electrons, 290, 294, 312, 328, 333, 344, 355, 356 Electrophysiological, 35, 49, 161, 312 Electroshock, 312, 317 Elementary Particles, 312, 333, 342, 353 Embolism, 156, 312 Embolus, 171, 267, 312, 325 Embryo, 299, 312, 325 Embryology, 312, 341 Emesis, 168, 312, 324 Emetic, 169, 312 Emphysema, 301, 312 Empirical, 39, 312 Emulsion, 293, 312, 317 Enamel, 308, 312 Encapsulated, 159, 312 Encephalitis, 185, 312, 313, 334 Encephalitis, Viral, 312 Encephalomyelitis, 176, 185, 313 Encephalopathy, 51, 62, 313

Endemic, 313, 333, 364 Endocrine System, 313, 340 Endocrinology, 9, 313 Endothelial cell, 26, 29, 295, 313, 317 Endothelium, 27, 313, 342, 349 Endothelium, Lymphatic, 313 Endothelium, Vascular, 313 Endothelium-derived, 313, 342 Endotoxic, 313, 331 Endotoxin, 144, 166, 313, 371 End-stage renal, 301, 313, 350 Enhancer, 161, 313 Entorhinal Cortex, 313, 322 Environmental Health, 224, 226, 313 Enzymatic, 297, 298, 303, 308, 313, 317, 358 Eosinophil, 184, 313 Eosinophilic, 313, 314 Epidemic, 30, 314, 364 Epidemiological, 29, 55, 79, 99, 187, 314 Epidermoid carcinoma, 314, 364 Epilepticus, 23, 314 Epinephrine, 286, 301, 310, 314, 342, 371 Epithelial, 294, 314, 329 Epithelial Cells, 314, 329 Epithelium, 294, 313, 314 Erection, 314, 351 Ergot, 296, 314 ERV, 137, 226, 314, 315 Erythema, 314, 365 Erythrocyte Volume, 295, 314 Erythrocytes, 289, 296, 297, 314, 356, 360 Esophagus, 309, 314, 348, 365, 368 Estrogen, 29, 31, 188, 189, 314, 352, 356, 360, 367 Estrogen receptor, 30, 188, 189, 314 Estrogen Receptor Modulators, 189, 314 Ethanol, 118, 314 Ethnic Groups, 189, 314 Evacuation, 24, 304, 315 Evoke, 61, 315, 365 Evoked Potentials, 71, 77, 110, 197, 315 Excitability, 49, 146, 166, 315 Excitation, 157, 315 Excitatory, 35, 105, 145, 146, 157, 166, 182, 315, 319, 320, 325, 329, 341, 355 Excitatory Amino Acid Agonists, 315, 329 Excitatory Amino Acids, 145, 315, 341 Excitotoxicity, 8, 315 Exhaustion, 315, 333 Exogenous, 315, 371 Exon, 287, 315 Expectorant, 315, 362

381

Expiration, 315, 357 Expiratory, 314, 315 Expiratory Reserve Volume, 314, 315 Extender, 45, 315 Extensor, 148, 315, 354 Extracellular, 35, 41, 49, 57, 59, 63, 152, 172, 179, 288, 292, 304, 315, 316, 317, 334, 335, 340, 362 Extracellular Matrix, 304, 315, 316, 317, 334 Extracellular Matrix Proteins, 316, 334 Extracellular Space, 315, 316, 335 Extraction, 18, 316 Extrapyramidal, 288, 290, 310, 316 Extravasation, 316, 321 Extremity, 96, 186, 214, 316, 346, 359 Eye Infections, 164, 316 F Facial, 74, 234, 316, 334, 362 Facial Paralysis, 234, 316 Faecal, 309, 316 Family Planning, 225, 316 Family Relations, 235, 316 Fat, 120, 291, 295, 298, 305, 307, 312, 316, 331, 337, 358, 362 Fatigue, 34, 192, 316, 321, 339 Fatty acids, 81, 127, 311, 316, 331, 352, 362, 368 Febrile, 316, 333, 355, 364 Feces, 304, 316, 365 Feeding Behavior, 161, 316 Fibrillation, 243, 248, 267, 307, 316 Fibrin, 295, 316, 317, 347, 349, 368 Fibrinogen, 316, 317, 349, 368 Fibrinolytic, 317, 368 Fibrinolytic Agents, 317, 368 Fibroblast Growth Factor, 11, 317 Fibroblasts, 151, 155, 317, 327 Fibrosis, 149, 183, 287, 317, 359 Fissure, 308, 317, 351 Fixation, 317, 360 Flatus, 317, 318 Flexion, 154, 317 Flexor, 148, 315, 317 Fluid Therapy, 317, 343 Flurothyl, 24, 317 Focus Groups, 16, 317 Fold, 32, 317, 318 Forearm, 295, 318 Fossa, 300, 318 Fourth Ventricle, 318, 332, 368 Friction, 287, 318

Frontal Lobe, 43, 117, 158, 290, 300, 318, 351 Functional magnetic resonance imaging, 10, 30, 60, 82, 318 Fundus, 317, 318, 343 Fungi, 316, 318, 335, 336, 374 G Gait, 106, 318 Gallbladder, 285, 294, 318 Gamma Rays, 318, 355, 356 Ganglia, 160, 169, 285, 293, 318, 339, 345, 347, 366 Gap Junctions, 318, 366 Gas, 152, 161, 288, 297, 309, 314, 317, 318, 323, 328, 342, 355, 357, 372 Gas exchange, 318, 357, 372 Gastric, 293, 298, 318 Gastrin, 318, 322 Gastrointestinal, 149, 161, 183, 255, 296, 301, 314, 318, 330, 333, 360, 362, 365 Gastrointestinal tract, 161, 301, 314, 318, 330, 360 Gelatin, 318, 320, 368 Gene, 13, 20, 22, 31, 32, 44, 46, 68, 179, 287, 288, 295, 319, 349, 353 Gene Expression, 20, 179, 319 Generator, 186, 319 Genetic Code, 319, 343 Genetic Techniques, 29, 319 Genetics, 23, 319 Genotype, 31, 32, 65, 67, 319, 348 Geriatric, 249, 254, 260, 263, 266, 319 Germ Cells, 319, 334, 344, 362 Gland, 9, 33, 286, 319, 332, 345, 349, 353, 356, 359, 365, 368 Glasgow Coma Scale, 25, 74, 148, 154, 319 Gliosis, 27, 319 Glomerular, 319, 333, 357 Glomerular Filtration Rate, 319, 333 Glucocorticoid, 319, 323 Gluconeogenesis, 319 Glucose, 12, 41, 161, 163, 169, 173 Glucose Intolerance, 309, 319 Glutamate, 8, 54, 63, 121, 146, 166, 315, 319, 320, 329, 335 Glutamic Acid, 57, 145, 320, 352 Glycine, 145, 182, 183, 320, 360 Glycogen, 54, 162, 163, 169, 173, 320, 348 Glycogen Synthase, 54, 162, 163, 169, 173, 320 Glycolysis, 41, 320 Glycoprotein, 317, 320, 329, 337, 371

382


Glycosaminoglycans, 316, 320, 353 Gonadal, 320, 364 Governing Board, 320, 351 Grade, 320 Grading, 148, 320 Graft, 150, 158, 320, 323, 338 Grafting, 155, 320, 325 Granule, 308, 320, 358 Granulocytes, 294, 320, 330, 361, 374 Gravis, 159, 176, 320 Growth, 14, 34, 54, 58, 137, 155, 163, 169, 173, 179, 184 Growth factors, 163, 169, 173, 320 Guanylate Cyclase, 320, 342 H Habitual, 300, 320 Haematemesis, 312, 320 Haematoma, 321 Haemorrhage, 156, 321 Hallucinogen, 321, 348 Haptens, 286, 321 Headache, 55, 168, 244, 251, 252, 260, 262, 264, 282, 321, 323, 324, 326 Headache Disorders, 321 Health Care Costs, 27, 321 Health Expenditures, 321 Health Resources, iv, 7, 47, 135, 321 Health Services, iv, 7, 226, 239, 308, 321, 367 Health Status, 17, 321 Hearing Disorders, 303, 321 Heart Arrest, 298, 321 Heart attack, 181, 298, 321 Heart failure, 184, 321 Hematology, 29, 321 Hematoma, 25, 159, 175, 187, 231, 232, 321 Heme, 92, 307, 321, 345 Hemiparesis, 296, 322 Hemodilution, 26, 322 Hemodynamics, 9, 33, 100, 129, 322 Hemoglobin, 164, 289, 314, 321, 322 Hemostasis, 322, 360 Hepatic, 258, 308, 322 Hereditary, 301, 322, 337, 339 Heredity, 319, 322 Heterogeneity, 15, 42, 286, 322 Hippocampus, 19, 23, 35, 54, 56, 121, 127, 128, 161, 308, 322, 331, 340, 355, 365 Histology, 8, 21, 322, 340 Homeostasis, 49, 57, 63, 161, 322, 362 Homogeneous, 305, 322 Homologous, 287, 322, 360, 366

Hormonal, 9, 292, 301, 322 Hormone, 26, 34, 53, 241, 270 Hormone Replacement Therapy, 241, 322 Hormone therapy, 270, 323 Hospital Administration, 60, 323 Host, 150, 293, 323, 325, 330, 373 Housekeeping, 29, 323 Hybridomas, 323, 327 Hydrocephalus, 323, 328 Hydrocortisone, 9, 34, 323 Hydrogen, 168, 285, 288, 294, 297, 308, 316, 323, 331, 336, 342, 344, 347, 353, 366 Hydrogen Peroxide, 323, 331, 366 Hydrolysis, 145, 292, 323, 348, 350, 353 Hydroxylysine, 303, 323 Hydroxyproline, 303, 323 Hygienic, 323, 361 Hyperalgesia, 146, 166, 323 Hypercapnia, 121, 323 Hyperesthesia, 55, 323 Hyperlipidaemia, 239, 323 Hyperoxia, 91, 323 Hypersensitivity, 287, 313, 324, 330, 358, 360, 361 Hypertension, 25, 149, 158, 162, 163, 169, 173, 183, 253, 257 Hypertensive Encephalopathy, 51, 324 Hyperthermia, 90, 116, 152, 153, 324 Hyperthyroidism, 247, 324 Hypertrophy, 294, 305, 324 Hyperventilation, 8, 84, 91, 121, 150, 212, 324 Hypoglycaemia, 308, 324 Hypoglycemia, 40, 145, 181, 324 Hypophysis, 324, 360 Hypotension, 9, 26, 33, 63, 102, 164, 290, 305, 324 Hypothalamic, 9, 34, 92, 324 Hypothalamus, 160, 293, 296, 309, 324, 331, 349, 368 Hypothermia, 28, 54, 64, 71, 92, 94, 100, 102, 152, 153, 185, 212, 213, 322, 324 Hypothyroidism, 247, 324 Hypotonic Solutions, 324, 336 Hypoxia, 23, 26, 97, 159, 164, 231, 308, 324 I Ibotenic Acid, 145, 324 Idiopathic, 6, 325 Ileum, 325, 329 Illusion, 325, 373 Immune response, 290, 293, 321, 325, 360, 365, 373

383

Immune Sera, 325 Immune system, 26, 293, 294, 311, 325, 330, 332, 337, 371, 374 Immunization, 249, 255, 325, 351, 360 Immunodeficiency, 163, 169, 173, 325 Immunogenic, 325, 331 Immunoglobulin, 258, 290, 325 Immunohistochemistry, 63, 325 Immunologic, 31, 300, 325, 356 Immunology, 184, 286, 325 Implantation, 155, 243, 325 In vitro, 10, 12, 29, 46, 53, 57, 59, 119, 128, 137, 155, 162, 169, 173, 295, 325 Incision, 325, 328 Incontinence, 109, 145, 149, 168, 181, 183, 240, 323, 325, 359 Indicative, 175, 193, 325, 346, 372 Induction, 13, 29, 35, 46, 55, 92, 151, 153, 290, 312, 325, 329, 352 Infarction, 24, 25, 171, 184, 239, 259, 271, 300, 325, 357 Infection Control, 269, 326 Infertility, 296, 326 Infestation, 326, 346 Inflammatory bowel disease, 150, 163, 168, 169, 170, 184, 326 Influenza, 242, 288, 326 Infusion, 53, 326, 338, 370 Ingestion, 326, 350 Inhalation, 326, 350 Initiation, 21, 54, 326, 369 Initiator, 12, 326 Inlay, 326, 357 Innervation, 25, 326, 347, 359, 369 Inorganic, 149, 184, 326, 337, 342 Inositol, 326, 335, 359 Inotropic, 310, 326 Insight, 15, 20, 42, 326 Insomnia, 188, 266, 327 Instillation, 185, 327 Insulator, 327, 337 Insulin, 40, 137, 163, 169, 173, 327, 371 Insulin-dependent diabetes mellitus, 327 Insulin-like, 137, 327 Intensive Care, 9, 18, 20, 35, 47, 150, 154, 158, 327 Intensive Care Units, 20, 35, 154, 327 Interferon, 176, 184, 327 Interferon-alpha, 327 Interleukin-1, 32, 150, 184, 327 Interleukin-2, 144, 166, 327 Interleukin-6, 92, 104, 327

Intermittent, 149, 183, 317, 327, 332 Internal Medicine, 28, 117, 120, 313, 321, 327 Interstitial, 8, 316, 324, 327, 357 Intervertebral, 327, 332 Intervertebral Disk Displacement, 327, 332 Intestine, 296, 328, 356, 362 Intoxication, 308, 328, 372, 374 Intracranial Hypertension, 8, 24, 84, 85, 86, 88, 90, 93, 164, 321, 323, 328, 369 Intracranial Pressure, 20, 25, 56, 126, 149, 150, 153, 158, 159, 162, 164, 187 Intramuscular, 186, 328, 346 Intrathecal, 159, 328 Intravenous, 54, 61, 258, 326, 328, 346 Intrinsic, 20, 38, 49, 179, 286, 294, 328 Intubation, 78, 105, 256, 299, 328 Invasive, 42, 46, 55, 328, 333 Involuntary, 293, 301, 311, 316, 328, 338, 357, 363, 369 Iodine, 237, 328, 362 Iodine-131, 237, 328 Ion Channels, 145, 149, 184, 292, 328, 340, 341, 366 Ionization, 328 Ionizing, 178, 287, 328, 356 Ions, 57, 145, 149, 178, 184, 294, 297, 310, 311, 323, 328, 350, 362 Irritable Bowel Syndrome, 149, 170, 183, 328 Ischemic stroke, 18, 59, 182, 239, 248, 329 Isotonic, 329, 336 J Jejunum, 169, 329 Joint, 186, 188, 235, 238, 248, 253, 292, 317, 329, 332, 344, 364 K Kainate, 19, 146, 166, 182, 183, 309, 329 Kainic Acid, 145, 329 Kb, 224, 329 Keratolytic, 308, 329 Ketamine, 95, 329, 348 Kidney Disease, 149, 183, 224, 258, 329 Kidney Failure, 313, 329, 333 Kinetic, 328, 329 L Labile, 303, 329 Laminin, 179, 294, 316, 329 Language Development, 236, 329, 330 Language Development Disorders, 329, 330

384


Language Disorders, 7, 235, 303, 330, 363 Language Therapy, 235, 330 Laparoscopy, 255, 330 Larynx, 330, 369, 372 Latency, 24, 330 Latent, 23, 242, 330, 351 Latent period, 23, 330 Length of Stay, 25, 330 Lens, 298, 330 Lesion, 12, 30, 36, 43, 107, 172, 201, 319, 330, 331, 360, 371 Lethal, 78, 105, 122, 174, 293, 306, 330 Lethargy, 282, 323, 324, 330 Leucocyte, 313, 330 Leukemia, 184, 301, 330, 351 Leukocytes, 59, 296, 300, 320, 327, 330, 336, 371 Leukopenia, 185, 330 Leukotrienes, 291, 311, 330, 331 Library Services, 278, 330 Lice, 269, 330, 346 Life cycle, 295, 318, 331 Life Expectancy, 138, 331 Ligament, 331, 353, 364 Ligands, 21, 145, 331 Limbic, 35, 288, 331, 351 Limbic System, 288, 331, 351 Linkages, 47, 320, 322, 331 Lipid, 50, 119, 130, 177, 258, 300, 327, 331, 337, 345 Lipid A, 50, 331 Lipid Peroxidation, 50, 119, 130, 177, 331, 345 Lipopolysaccharides, 331 Lipoxygenase, 177, 291, 330, 331, 342 Lipoxygenase Inhibitors, 177, 331 Liver, 258, 285, 291, 294, 297, 298, 312, 316, 318, 320, 322, 331, 337, 345, 359 Liver scan, 331, 359 Lobe, 43, 65, 117, 158, 300, 331 Localization, 21, 56, 325, 331 Localized, 46, 289, 296, 308, 312, 317, 321, 326, 329, 331, 339, 349, 371 Locomotion, 39, 331, 332, 349 Locomotor, 106, 332 Locus Coeruleus, 57, 332 Longitudinal study, 47, 48, 49, 65, 75, 76, 332 Long-Term Care, 162, 332 Long-Term Potentiation, 46, 332 Low Back Pain, 239, 246, 332 Lucida, 329, 332

Lumbar, 159, 293, 327, 332, 359, 369 Lung volume, 153, 332 Lupus, 238, 303, 332 Luxation, 310, 332 Lymph, 300, 302, 313, 332 Lymph node, 300, 332 Lymphatic, 313, 326, 332, 350, 362, 368 Lymphocyte, 290, 332, 334 Lymphoid, 290, 306, 330, 332 M Macrophage, 176, 177, 327, 332 Macula, 332, 333 Macula Lutea, 333 Macular Degeneration, 163, 333 Magnetic Resonance Imaging, 9, 10, 30, 60, 66, 76, 90, 97, 104, 333, 359 Magnetic Resonance Spectroscopy, 42, 55, 116, 117, 119, 122, 333 Malaria, 178, 333 Malaria, Falciparum, 333 Malaria, Vivax, 333 Malignant, 78, 157, 176, 324, 333, 337, 339, 356 Malignant tumor, 333, 337 Malingering, 110, 333 Malnutrition, 292, 297, 333 Mammary, 333, 356, 367 Mandible, 287, 333, 357 Mania, 159, 333 Manic, 290, 295, 333, 354 Manic-depressive psychosis, 333, 354 Manifest, 46, 97, 293, 333 Mannitol, 8, 52, 97, 150, 333 Mastication, 334, 370 Matrix metalloproteinase, 30, 334 Meatus, 334, 372 Medial, 26, 160, 334, 343, 358, 363, 369 Mediate, 39, 47, 50, 57, 62, 145, 169, 310, 334, 355 Mediator, 24, 46, 144, 166, 184, 327, 334, 360 Medicament, 144, 165, 334 MEDLINE, 225, 334 Meiosis, 334, 366 Melanin, 332, 334, 348, 371 Melanocytes, 334 Melanoma, 151, 334 Membrane Glycoproteins, 334 Memory Disorders, 160, 334 Meninges, 299, 306, 311, 334 Meningitis, 62, 132, 334 Menopause, 270, 334, 350

385

Menstrual Cycle, 334, 352 Menstruation, 288, 311, 334, 335, 343 Mental Disorders, 265, 330, 335, 351, 354 Mental Health, iv, 7, 159, 224, 226, 239, 259, 335, 351, 354 Mental Processes, 310, 335, 354 Mental Retardation, 151, 265, 303, 335 Mentors, 9, 47, 335 Mesencephalic, 161, 332, 335, 356 Metabolite, 309, 335, 351 Metabotropic, 121, 145, 146, 166, 335, 355 Metastasis, 334, 335, 339 Metatarsophalangeal Joint, 253, 335 Methionine, 309, 335 Methylphenidate, 10, 31, 78, 335 MI, 116, 168, 283, 335 Microbe, 335, 369 Microbiology, 286, 292, 335 Microcirculation, 322, 335, 349 Microdialysis, 8, 57, 63, 335 Micronutrients, 157, 335 Microorganism, 302, 336, 373 Micro-organism, 308, 336 Microscopy, 11, 18, 294, 336, 343 Microtubule-Associated Proteins, 336, 340, 367 Microtubules, 336, 340, 367 Middle Cerebral Artery, 59, 336 Migration, 102, 336, 340 Mitochondria, 12, 39, 40, 50, 121, 336, 338, 344 Mitochondrial Swelling, 39, 336, 339 Mitosis, 291, 336 Mobility, 161, 336 Mobilization, 336, 355 Modeling, 49, 97, 174, 336 Modification, 7, 37, 336, 355 Modulator, 54, 182, 183, 188, 336 Molecular, 10, 11, 13, 29, 32, 35, 39, 45, 46, 59, 61, 116, 119, 139, 175, 225, 227 Molecule, 290, 294, 302, 303, 310, 311, 313, 315, 323, 336, 344, 348, 353, 356, 361, 372 Monitor, 53, 56, 92, 306, 336, 343 Monoamine, 170, 171, 288, 309, 336 Monocytes, 60, 185, 327, 330, 336 Mononuclear, 144, 166, 336, 337, 371 Monophosphate, 170, 337 Mood Disorders, 43, 96, 337 Morphological, 44, 61, 312, 334, 337, 341 Morphology, 26, 299, 321, 337 Motility, 337, 360 Motion Sickness, 168, 337, 339, 359

Motor Activity, 305, 337 Motor nerve, 337, 343 Motor Neurons, 56, 337 Motor Skills, 106, 160, 337 Movement Disorders, 147, 288, 290, 311, 337, 367 Mucociliary, 337, 361 Mucolytic, 285, 337 Mucosa, 332, 337, 352, 365 Mucus, 315, 337, 358, 371 Multiple Myeloma, 184, 337 Multiple Organ Failure, 120, 337 Multiple sclerosis, 36, 158, 163, 168, 176, 177, 337 Multiple Trauma, 9, 111, 337 Muscle Relaxation, 337, 340 Muscular Diseases, 316, 337 Musculature, 338, 364 Musculoskeletal System, 338, 344 Myalgia, 326, 338 Myasthenia, 159, 176, 338 Mydriatic, 338, 359 Myelin, 62, 178, 308, 337, 338, 340 Myelodysplastic syndrome, 184, 338, 362 Myelogenous, 184, 338 Myeloma, 184, 260, 338 Myocardial infarction, 171, 184, 239, 259, 271, 306, 335, 338 Myocardial Ischemia, 289, 338 Myocardial Reperfusion, 338, 357 Myocardial Reperfusion Injury, 338, 357 Myocardium, 289, 335, 338 Myofibrils, 297, 338 Myopathy, 159, 338 N N-acetyl, 55, 117, 121, 285, 320, 338 Narcolepsy, 149, 171, 183, 188, 309, 335, 338 Nasal Mucosa, 326, 338 Nasopharynx, 238, 338 Nausea, 55, 290, 324, 339, 353, 371 Neck Pain, 245, 339 Necrosis, 9, 21, 34, 144, 165, 166, 172, 176, 291, 296, 300, 325, 335, 338, 339, 357 Neocortex, 19, 339, 340 Neonatal, 35, 248, 254, 271, 339 Neoplasms, 323, 339, 356, 367 Neoplastic, 323, 339 Nephropathy, 329, 339 Nerve Endings, 339, 342 Nerve Fibers, 160, 175, 178, 179, 339, 369 Networks, 35, 160, 339

386


Neural Pathways, 30, 339 Neuralgia, 188, 339, 350 Neurasthenia, 55, 339 Neuroanatomy, 60, 331, 339 Neurobehavioral Manifestations, 296, 309, 339 Neurodegenerative Diseases, 146, 167, 178, 180, 293, 339 Neuroendocrine, 9, 34, 120, 340 Neuroendocrinology, 9, 340 Neurofibrillary Tangles, 340, 341, 367 Neurogenic, 99, 199, 205, 209, 340 Neuroglia, 319, 340 Neuroleptic, 78, 290, 340 Neurology, 18, 24, 29, 40, 61, 117, 118, 120, 121, 126, 127, 128, 131, 185, 187, 248, 249, 264, 265 Neuromuscular, 89, 186, 285, 316, 340, 371 Neuromuscular Blockade, 89, 340 Neuromuscular Junction, 285, 340 Neuropeptide, 169, 341 Neurophysiology, 41, 56, 93, 308, 341 Neuropil, 341, 367 Neuropil Threads, 341, 367 Neuroprotective Agents, 10, 145, 341 Neuropsychological Tests, 47, 100, 341 Neuropsychology, 30, 68, 73, 75, 76, 77, 78, 95, 97, 99, 102, 105, 107, 116, 196, 341 Neurosciences, 19, 67, 102, 119, 122, 341 Neurosis, 341 Neurosurgeon, 25, 56, 87, 341 Neurosurgery, 10, 18, 19, 25, 116, 120, 121, 122, 129, 147, 171, 187, 231 Neurotic, 55, 341 Neurotoxic, 29, 57, 63, 176, 324, 341 Neurotoxicity, 32, 178, 329, 341 Neurotoxin, 156, 341 Neurotransmitters, 27, 145, 146, 160, 166, 170, 315, 337, 341, 362 Neutrons, 287, 342, 355 Neutrophil, 182, 183, 184, 342 Neutrophil Activation, 184, 342 Nicotine, 15, 168, 188, 189, 342 Nimodipine, 63, 342 Nitric Oxide, 13, 28, 31, 121, 176, 182, 183, 342 Nitrogen, 50, 176, 287, 288, 316, 317, 342, 370 Nitrogen Dioxide, 50, 342 Nitrogen Oxides, 176, 342 Nociceptors, 146, 166, 342 Nonverbal Communication, 303, 342, 354

Nordihydroguaiaretic Acid, 176, 342 Norepinephrine, 57, 171, 286, 310, 342 Nuclear, 74, 119, 144, 166, 177, 237, 268, 293, 312, 316, 318, 331, 339, 343, 368 Nuclear Family, 316, 343 Nuclei, 41, 160, 287, 288, 290, 312, 316, 331, 333, 336, 342, 343, 353, 373 Nucleic acid, 50, 152, 172, 181, 319, 342, 343, 355 Nucleolus, 343, 358 Nursing Care, 20, 343 Nutritional Support, 122, 263, 343 O Observer Variation, 15, 343 Occult, 122, 343 Ocular, 168, 343 Oculomotor, 43, 335, 343 Ointments, 343, 361, 362 Oligomenorrhea, 343, 350 Oliguria, 329, 333, 343 Opacity, 298, 343 Operating Rooms, 154, 343 Opsin, 343, 358 Optic Chiasm, 324, 343 Optic Disk, 309, 333, 343, 345 Organelles, 307, 334, 337, 344 Orthopaedic, 72, 243, 257, 344 Orthotic Devices, 186, 344 Osmolarity, 334, 344 Osmosis, 344 Osmotic, 52, 324, 336, 344 Osteoarthritis, 170, 184, 255, 344 Osteoporosis, 230, 257, 344, 356 Otitis, 253, 344 Otitis Media, 253, 344 Outpatient, 23, 34, 129, 213, 344 Ovaries, 344, 350 Ovary, 163, 169, 173, 306, 344, 365 Overexpress, 13, 344 Ovum, 306, 331, 344, 352 Oxidation, 285, 290, 291, 306, 307, 331, 344, 345 Oxidative metabolism, 42, 286, 330, 344 Oxidative Stress, 39, 53, 116, 117, 344 Oxides, 176, 342, 345 Oxygen Consumption, 345, 357 Oxygenase, 92, 345 Oxygenation, 18, 46, 87, 91, 345 P Pacemaker, 345 Pachymeningitis, 334, 345 Paediatric, 72, 345

387

Palate, 338, 345 Palliative, 157, 259, 345, 368 Palsy, 49, 151, 158, 186, 230, 345 Pancreas, 285, 327, 345 Pancreatic, 298, 345 Pancreatitis, 184, 345 Papilledema, 324, 345, 353 Paraganglia, Chromaffin, 301, 345 Paralysis, 186, 234, 291, 297, 316, 322, 335, 345, 346, 363 Paranasal Sinuses, 345, 361 Parasitic, 326, 330, 345 Parenchyma, 57, 345 Parenteral, 120, 247, 346 Parenteral Nutrition, 120, 247, 346 Paresis, 316, 346 Parietal, 72, 290, 346, 347 Parietal Lobe, 290, 346 Paroxysmal, 267, 289, 321, 346 Partial response, 148, 346 Particle, 346, 363, 369 Patch, 35, 346 Pathogenesis, 28, 32, 144, 166, 184, 346 Pathologic, 285, 291, 294, 296, 305, 324, 346, 354, 357, 361 Pathologic Processes, 291, 346 Pathologies, 36, 346 Pathophysiology, 18, 19, 29, 50, 63, 79, 92, 138, 197, 203, 346 Patient Education, 234, 276, 278, 283, 346 Pediculosis, 269, 346 Penis, 346, 351 Peptide, 317, 346, 350, 353, 368 Perception, 7, 74, 138, 146, 167, 321, 346, 359 Percutaneous, 186, 346 Perennial, 347, 370 Perforation, 291, 347 Perfusion, 8, 20, 27, 33, 52, 60, 89, 126, 158, 162, 164, 185, 241, 268, 324, 347 Perioperative, 31, 243, 347 Peripheral blood, 185, 327, 347, 351 Peripheral Nerves, 156, 347, 364 Peripheral Nervous System, 179, 308, 311, 340, 345, 347, 365 Peritoneum, 347 Peritonitis, 184, 347 Perivascular, 26, 347 Peroneal Nerve, 347, 359 Petechiae, 321, 347 PH, 10, 268, 347 Phagocytosis, 177, 347

Pharmacodynamic, 24, 347 Pharmacokinetic, 24, 347 Pharmacologic, 13, 20, 36, 43, 120, 262, 289, 347, 369 Pharmacotherapy, 19, 27, 108, 176, 347 Pharyngitis, 246, 262, 347 Pharynx, 324, 326, 338, 347, 372 Phencyclidine, 145, 348 Phenotype, 176, 348 Phenyl, 156, 168, 348 Phenylalanine, 348, 371 Phosphodiesterase, 170, 348 Phospholipases, 348, 361 Phospholipids, 316, 326, 348 Phosphorus, 297, 348 Phosphorylase, 297, 348 Phosphorylated, 63, 302, 341, 348 Phosphorylation, 63, 163, 169, 173, 348 Photocoagulation, 302, 348 Physical Therapy, 6, 19, 105, 161, 199, 348 Physiologic, 20, 33, 52, 57, 287, 294, 309, 329, 334, 335, 339, 348, 352, 356, 357, 370 Physiology, 19, 33, 46, 49, 74, 116, 118, 178, 235, 312, 313, 321, 341, 348, 372 Pigment, 334, 348 Pilot study, 22, 24, 25, 53, 348 Pitch, 348, 374 Pituitary Gland, 34, 317, 349 Pituitary Hormones, 144, 166, 349 Placenta, 349, 352 Plague, 34, 349 Plants, 287, 292, 297, 300, 302, 319, 337, 342, 349, 359, 369, 370, 372 Plaque, 288, 349 Plasma, 178, 290, 295, 299, 313, 315, 317, 318, 319, 322, 323, 324, 329, 337, 338, 349 Plasma cells, 290, 337, 338, 349 Plasma Volume, 295, 349 Plasmin, 317, 349 Plasminogen, 239, 317, 349 Plasminogen Activators, 349 Plasticity, 19, 22, 46, 54, 56, 61, 147, 160, 349 Platelet Activation, 349, 361 Platelet Aggregation, 164, 289, 342, 349, 353, 368 Platelets, 164, 291, 297, 342, 349, 368 Plexus, 350, 359 Poisoning, 157, 308, 314, 328, 339, 350, 360 Polycystic, 149, 163, 169, 173, 183, 350 Polycystic Ovary Syndrome, 163, 169, 173, 350

388


Polymorphic, 308, 350 Polypeptide, 181, 288, 298, 303, 317, 349, 350, 352 Polysaccharide, 290, 350, 353 Pons, 127, 296, 316, 318, 350, 358 Port, 149, 350 Port-a-cath, 350 Posterior, 42, 153, 186, 289, 292, 293, 300, 310, 339, 345, 349, 350, 359, 363 Postherpetic Neuralgia, 288, 350 Postmenopausal, 270, 344, 350, 356 Postnatal, 54, 350 Postoperative, 337, 350 Postsynaptic, 63, 350, 361, 366 Post-traumatic, 9, 17, 19, 23, 32, 34, 49, 50, 158, 162, 164, 176, 187 Post-traumatic stress disorder, 71, 101, 350 Potassium, 27, 41, 57, 148, 149, 177, 178, 182, 183, 262, 350, 362 Potassium Channels, 27, 57, 149, 178, 183, 350 Potentiate, 36, 350 Potentiation, 46, 301, 332, 350, 361 Practice Guidelines, 199, 226, 237, 238, 243, 251, 254, 258, 351 Preclinical, 27, 43, 93, 146, 166, 351 Precursor, 44, 150, 291, 300, 310, 311, 313, 342, 348, 349, 351, 370, 371 Predictive factor, 93, 351 Predisposition, 31, 351 Prefrontal Cortex, 9, 351 Pregnenolone, 44, 351 Preleukemia, 338, 351, 362 Premedication, 351, 359 Presynaptic, 63, 339, 351, 366, 367 Prevalence, 51, 71, 96, 120, 140, 235, 236, 351 Priapism, 238, 351 Primary Prevention, 249, 351 Probe, 46, 335, 351 Problem Solving, 9, 175, 351 Prodrug, 184, 351 Progesterone, 43, 52, 53, 351, 352, 364 Progestogen, 270, 352 Prognostic factor, 108, 352 Progression, 29, 45, 55, 72, 168, 172, 175, 289, 352 Progressive, 45, 49, 56, 62, 155, 158, 168, 174, 189, 299, 301, 308, 310, 320, 337, 339, 340, 344, 349, 352, 357 Projection, 342, 351, 352, 355, 356

Prolactin, 296, 352 Proline, 303, 323, 352 Prone, 23, 38, 160, 352 Prophase, 352, 366 Prophylaxis, 86, 188, 249, 308, 351, 352 Propofol, 95, 352 Proportional, 63, 150, 352 Prospective study, 6, 66, 72, 332, 352 Prostaglandin, 164, 352, 353, 368 Prostaglandin Endoperoxides, 164, 353, 368 Prostaglandins A, 352, 353 Prostate, 294, 353 Prostate gland, 353 Prostatic Hyperplasia, 168, 353 Prosthesis, 151, 161, 353 Protease, 150, 303, 353 Protein Isoforms, 287, 353 Protein S, 54, 288, 295, 319, 353, 358 Proteinuria, 337, 353 Proteoglycan, 184, 353 Proteolytic, 303, 317, 349, 353 Protocol, 25, 36, 64, 254, 255, 257, 353 Protons, 40, 287, 323, 328, 333, 353, 355 Proximal, 310, 351, 353 Pseudotumor Cerebri, 328, 353 Psoriasis, 150, 163, 170, 184, 354 Psychiatric, 43, 72, 102, 137, 147, 156, 158, 192, 213, 256, 262, 263, 303, 335, 354 Psychiatry, 30, 42, 43, 45, 187, 263, 264, 265 Psychic, 341, 354, 360 Psychology, 5, 16, 27, 30, 38, 56, 90, 96, 137, 310, 341, 354 Psychomotor, 307, 340, 354 Psychophysiology, 341, 354 Psychosis, 80, 149, 168, 183, 290, 354 Psychosomatic, 168, 354 Psychotherapy, 128, 203, 354 Psychotomimetic, 288, 309, 354 Psychotropic, 91, 118, 128, 354 Public Health, 16, 27, 32, 47, 189, 195, 226, 272, 354 Public Policy, 225, 354 Publishing, 64, 191, 192, 205, 354 Pulmonary, 185, 269 Pulmonary Artery, 295, 354, 372 Pulmonary Edema, 185, 329, 355 Pulmonary Ventilation, 324, 355 Pulse, 51, 186, 336, 355 Purines, 355, 360 Purpura, 321, 355 Pyramidal Cells, 308, 355

389

Pyrexia, 164, 355 Q Quality of Life, 9, 31, 34, 37, 43, 51, 67, 89, 108, 126, 131, 140, 157, 355 Quaternary, 355, 359 Quiescent, 176, 355 Quisqualic Acid, 145, 355 R Race, 163, 336, 355 Radiation, 178, 238, 262, 289, 293, 310, 312, 318, 324, 328, 355, 356, 359, 365, 374 Radiation therapy, 310, 355 Radioactive, 293, 296, 323, 325, 328, 331, 343, 355, 356, 359, 362 Radiography, 261, 355 Radioimmunotherapy, 355, 356 Radiological, 231, 346, 356 Radiology, 18, 55, 119, 196, 231, 244, 245, 246, 356 Radiopharmaceutical, 319, 356 Radiotherapy, 243, 355, 356, 364 Raloxifene, 356, 360 Randomized, 9, 17, 24, 25, 34, 50, 53, 60, 65, 66, 90, 102, 118, 128, 311, 356 Rape, 350, 356 Reaction Time, 98, 356 Reactive Oxygen Species, 50, 163, 176, 200, 356 Reality Testing, 354, 356 Receptor, 11, 12, 15, 30, 36, 46, 53, 57, 63, 68, 112, 121, 139, 145, 146, 150, 151, 163, 166, 167, 169, 170, 173, 181, 182, 183, 188, 189, 286, 290, 310, 315, 329, 335, 356, 360, 361 Receptors, Serotonin, 356, 360 Recombinant, 150, 356, 372 Recovery of Function, 19, 26, 52, 56, 160, 179, 356 Rectum, 296, 309, 317, 318, 325, 326, 353, 356, 361 Recurrence, 295, 301, 333, 356 Red blood cells, 314, 345, 356, 359 Red Nucleus, 292, 356 Refer, 1, 297, 303, 310, 317, 318, 331, 332, 340, 342, 354, 356 Reflex, 148, 169, 357 Refraction, 357, 363 Refractory, 25, 311, 357 Regeneration, 81, 180, 317, 357 Regimen, 116, 306, 311, 347, 357 Rehabilitative, 17, 36, 108, 137, 203, 357 Reliability, 23, 94, 105, 154, 357

Remission, 295, 333, 356, 357 Renal failure, 308, 357 Reperfusion, 60, 172, 183, 338, 357 Reperfusion Injury, 60, 357 Research Design, 48, 357 Resorption, 184, 323, 357 Respiration, 6, 148, 291, 297, 336, 357 Respiratory distress syndrome, 163, 170, 357 Respiratory failure, 152, 153, 357 Restitution, 17, 357 Restoration, 16, 30, 60, 121, 213, 338, 348, 357, 374 Resuscitation, 59, 62, 87, 102, 118, 152, 153, 164, 298, 357 Reticular, 147, 160, 358 Reticular Formation, 147, 160, 358 Retina, 304, 309, 330, 333, 340, 343, 358, 371 Retinal, 176, 309, 324, 343, 344, 358 Retinal Hemorrhage, 324, 358 Retinol, 358 Retinopathy, 164, 309, 358 Retrospective, 65, 358 Rheumatism, 358 Rheumatoid, 163, 168, 169, 170, 184, 303, 358 Rheumatoid arthritis, 163, 168, 169, 170, 184, 303, 358 Rhinitis, 168, 269, 358 Rhinorrhea, 149, 183, 358 Ribonuclease, 63, 358 Ribose, 286, 358 Ribosome, 54, 358, 370 Rigidity, 188, 328, 349, 358 Risk factor, 65, 109, 111, 129, 139, 206, 213, 250, 352, 358 Rod, 293, 302, 358 S Sagittal, 46, 358 Saline, 52, 60, 90, 102, 358 Salivary, 358, 374 Saponins, 359, 364 Scans, 25, 359 Schizoid, 359, 374 Schizophrenia, 147, 158, 188, 189, 334, 359, 374 Schizotypal Personality Disorder, 359, 374 Sciatic Nerve, 179, 347, 359, 369 Sclera, 304, 359, 371 Sclerosis, 36, 37, 145, 158, 163, 168, 175, 176, 177, 181, 303, 337, 359

390


Scopolamine, 122, 359 Screening, 62, 82, 106, 207, 233, 250, 258, 265, 270, 302, 359 Second Messenger Systems, 341, 359 Secretion, 149, 150, 164, 184, 286, 296, 301, 324, 327, 337, 349, 359 Secretory, 149, 183, 301, 359, 360, 366 Secretory Vesicles, 301, 360 Sedatives, Barbiturate, 293, 360 Seizures, 24, 62, 149, 178, 183, 184, 192, 235, 290, 308, 314, 324, 346, 360, 364 Selective estrogen receptor modulator, 188, 189, 356, 360, 367 Self Care, 285, 360 Sella, 9, 33, 310, 349, 360 Semisynthetic, 296, 360 Senile, 132, 145, 163, 181, 341, 344, 360 Sensibility, 288, 323, 360 Sensitization, 146, 167, 360 Sepsis, 15, 200, 360 Septic, 144, 166, 184, 360 Septicemia, 150, 360 Sequela, 141, 309, 360 Serine, 163, 169, 173, 360 Serotonin, 17, 36, 164, 171, 290, 347, 356, 360, 370 Serous, 313, 360 Sertraline, 17, 360 Serum, 9, 24, 53, 62, 69, 107, 212, 213, 289, 303, 325, 329, 347, 360, 371 Shock, 54, 59, 144, 152, 153, 158, 166, 184, 200, 312, 323, 360, 370 Shoulder Pain, 186, 243, 361 Side effect, 3, 44, 146, 167, 217, 219, 286, 290, 294, 310, 361, 369 Sigmoid, 38, 361 Sigmoid Colon, 361 Signal Transduction, 145, 326, 361 Sinusitis, 246, 361 Skeletal, 301, 302, 337, 338, 361, 363 Skeleton, 329, 352, 361 Skin Care, 254, 361 Skin Tests, 361, 370 Skull, 38, 58, 150, 159, 174, 175, 196, 234, 268, 271, 281, 306, 328, 361, 367 Skull Fracture, Depressed, 361, 362 Skull Fractures, 234, 361 Sleep apnea, 159, 362 Small intestine, 311, 322, 325, 328, 329, 362 Smoldering leukemia, 338, 362 Smooth muscle, 26, 57, 287, 289, 297, 337, 353, 362, 363, 365

Soaps, 361, 362 Social Environment, 14, 355, 362 Social Support, 4, 129, 196, 362 Sodium, 41, 145, 177, 178, 182, 183, 237, 362 Sodium Channels, 177, 178, 362 Sodium Iodide, 237, 362 Soft tissue, 295, 361, 362 Solid tumor, 289, 362 Solitary Nucleus, 160, 293, 362 Solvent, 285, 314, 344, 362 Soma, 355, 362 Somatic, 160, 331, 334, 336, 347, 351, 362, 372 Sorbitol, 333, 363 Sound wave, 304, 363 Spasm, 291, 335, 363 Spastic, 6, 82, 161, 186, 328, 363 Spasticity, 96, 188, 214, 363 Spatial disorientation, 310, 363 Specialist, 273, 363 Species, 176 Specificity, 62, 286, 291, 297, 351, 363 Spectrum, 28, 148, 193, 306, 363 Speech Disorders, 6, 209, 363 Speech Intelligibility, 36, 363 Speech pathologist, 5, 363 Speech-Language Pathology, 5, 6, 207, 363 Sperm, 301, 363, 371 Sphenoid, 345, 360, 363 Spina bifida, 49, 363 Spinal Cord Injuries, 78, 230, 363 Spinal Nerves, 347, 364 Spirochete, 364, 367 Spirometry, 6, 364 Sporadic, 339, 364 Sprains and Strains, 123, 332, 364 Sprue, 247, 364 Squamous, 238, 243, 314, 364 Squamous cell carcinoma, 238, 243, 314, 364 Squamous cells, 364 Stabilization, 263, 364 Staging, 359, 364 Status Epilepticus, 23, 364 Steady state, 53, 364 Steel, 302, 364, 372 Stereotactic, 41, 364 Sterile, 150, 364, 370 Sternum, 153, 364 Steroid, 26, 306, 351, 359, 364 Stimulant, 20, 239, 264, 288, 308, 335, 364

391

Stimulus, 154, 170, 297, 310, 311, 315, 326, 328, 330, 356, 357, 365, 368 Stomach, 285, 293, 309, 314, 318, 322, 339, 348, 362, 365 Stool, 325, 328, 365 Streptococcal, 262, 365 Streptococcus, 365 Striatum, 155, 365 Stroke Volume, 298, 365 Stroma, 346, 365 Stromal, 11, 18, 61, 365 Stromal Cells, 11, 18, 61, 365 Stupor, 330, 365 Subacute, 44, 326, 361, 365 Subarachnoid, 21, 56, 68, 91, 100, 122, 159, 171, 177, 318, 321, 365 Subclinical, 326, 360, 365 Subcutaneous, 311, 346, 365 Subiculum, 322, 365 Subspecies, 363, 365 Substance P, 306, 335, 352, 359, 365 Substrate, 179, 331, 365 Sunburn, 163, 365 Superoxide, 26, 119, 127, 365, 366 Superoxide Dismutase, 119, 127, 366 Supplementation, 27, 212, 366 Support group, 125, 273, 366 Suppression, 149, 183, 184, 366 Survival Rate, 236, 366 Sympathetic Nervous System, 293, 301, 341, 366 Sympathomimetic, 288, 309, 310, 314, 342, 366 Symptomatic, 71, 238, 288, 297, 345, 366 Symptomatic treatment, 238, 288, 366 Symptomatology, 51, 138, 366 Synapses, 26, 46, 301, 332, 342, 366, 367 Synapsis, 366 Synaptic, 28, 35, 49, 54, 146, 149, 166, 179, 184, 332, 341, 342, 361, 366, 367 Synaptic Transmission, 35, 149, 184, 342, 366 Synaptic Vesicles, 366, 367 Syncope, 148, 257, 367 Synergistic, 8, 45, 352, 367, 369 Synovial, 184, 367 Syphilis, 251, 367 Systolic, 324, 367 T Tamoxifen, 171, 360, 367 Tau Proteins, 104, 341, 367 Taurine, 59, 367

Telecommunications, 148, 367 Telemedicine, 37, 50, 367 Temporal, 13, 35, 49, 56, 176, 288, 321, 322, 333, 334, 367 Temporal Lobe, 288, 367 Tetrahydrocannabinol, 297, 367 Thalamic, 41, 161, 292, 367 Thalamic Diseases, 292, 367 Thalamus, 160, 296, 309, 331, 351, 367 Therapeutics, 15, 119, 163, 218, 235, 249, 368 Third Ventricle, 324, 367, 368 Thoracic, 31, 153, 171, 293, 309, 368, 374 Thoracic Surgery, 171, 368 Thorax, 153, 285, 332, 368, 372 Threonine, 163, 169, 173, 360, 368 Threshold, 20, 23, 56, 88, 315, 323, 324, 368 Thrombin, 316, 317, 349, 368 Thrombocytes, 350, 368 Thromboembolism, 263, 368 Thrombolytic, 248, 349, 368 Thrombolytic Therapy, 248, 368 Thrombosis, 28, 111, 353, 365, 368 Thromboxanes, 291, 311, 353, 368 Thrombus, 306, 325, 329, 338, 349, 368 Thymus, 325, 332, 368 Thyroid, 237, 242, 256, 258, 262, 268, 324, 328, 362, 368, 371 Thyroid Gland, 324, 368 Thyrotropin, 324, 368 Tibial Nerve, 359, 369 Tic, 111, 369 Tidal Volume, 324, 369 Tinnitus, 188, 344, 354, 369, 373 Tolerance, 54, 285, 319, 369 Tomography, 25, 41, 83, 231, 268, 333, 369 Tooth Preparation, 286, 369 Topical, 314, 323, 362, 369 Torsion, 326, 369 Toxic, iv, 178, 183, 292, 298, 306, 313, 342, 369 Toxicity, 44, 310, 369 Toxicology, 51, 121, 226, 369 Toxins, 290, 297, 312, 326, 355, 360, 369 Trachea, 296, 315, 330, 348, 368, 369 Traction, 302, 369 Trail Making Test, 110, 369 Transcription Factors, 151, 369 Transduction, 145, 361, 369 Transfection, 295, 370 Transfer Factor, 325, 370 Transfusion, 258, 315, 370

392


Transient Ischemic Attacks, 171, 370 Translation, 54, 370 Translocation, 177, 370 Transmitter, 285, 292, 310, 315, 328, 334, 340, 342, 366, 367, 370 Transplantation, 102, 155, 301, 325, 370 Trauma Centers, 87, 92, 187, 370 Trees, 46, 370 Tremor, 335, 370 Trigeminal, 188, 370 Trisomy, 288, 370 Trophic, 18, 61, 179, 370 Tryptophan, 303, 360, 370 Tubercle, 370 Tuberculin, 242, 370 Tuberculin Test, 242, 370 Tuberculosis, 242, 305, 306, 332, 370 Tubulin, 336, 367, 371 Tumor Necrosis Factor, 144, 165, 176, 371 Type 2 diabetes, 157, 250, 260, 371 Tyrosine, 163, 169, 173, 310, 371 U Ulcer, 266, 307, 371 Ulcerative colitis, 184, 326, 371 Unconscious, 147, 283, 289, 325, 371 Uraemia, 345, 371 Urethra, 294, 346, 353, 371 Urinary, 109, 145, 149, 168, 181, 183, 240, 301, 306, 323, 325, 343, 359, 371 Urinary tract, 306, 371 Urinary tract infection, 306, 371 Urinate, 371, 374 Urine, 294, 295, 305, 306, 310, 325, 343, 353, 371 Uterus, 300, 306, 317, 318, 335, 344, 352, 371 Uvea, 371 Uveitis, 184, 371 V Vaccine, 353, 371 Vagal, 160, 372 Vagus Nerve, 56, 148, 160, 362, 372 Valves, 153, 372 Vanadium, 63, 372 Vascular endothelial growth factor, 11, 372 Vascular Resistance, 26, 185, 372 Vasculitis, 345, 372 Vasoconstriction, 171, 314, 372 Vasodilatation, 57, 372 Vasodilator, 25, 27, 296, 310, 338, 372 Vasomotor, 25, 158, 162, 372

Vasopressor, 9, 34, 92, 372 Vector, 44, 150, 369, 372 Vegetative, 41, 116, 147, 231, 309, 372 Vein, 292, 328, 343, 372 Venereal, 367, 372 Venous, 41, 46, 95, 111, 263, 292, 296, 300, 353, 372 Venous blood, 296, 300, 372 Ventilation, 298, 372 Ventral, 23, 324, 343, 350, 364, 372 Ventricle, 288, 305, 322, 354, 355, 367, 372, 373 Ventricular, 56, 305, 323, 338, 373 Venules, 295, 313, 335, 373 Vertebrae, 327, 363, 373 Vertebral, 153, 294, 363, 373 Vertigo, 132, 246, 344, 373 Vestibulocochlear Nerve, 369, 373 Vestibulocochlear Nerve Diseases, 369, 373 Veterinary Medicine, 225, 373 Viral, 13, 44, 163, 241, 285, 312, 326, 369, 373 Viral vector, 13, 44, 373 Virulence, 292, 369, 373 Virus, 293, 299, 313, 327, 349, 369, 373 Viscera, 362, 373 Visceral, 160, 293, 331, 347, 372, 373 Visceral Afferents, 160, 293, 372, 373 Viscosity, 185, 285, 295, 373 Vitreous Hemorrhage, 309, 373 Vitro, 10, 12, 29, 46, 53, 57, 59, 119, 128, 137, 155, 162, 169, 173, 373 Vivo, 12, 13, 19, 25, 29, 31, 32, 38, 46, 53, 57, 59, 63, 119, 122, 128, 137, 162, 169, 173 Voice Quality, 7, 36, 373 Void, 43, 374 W Wakefulness, 307, 374 War, 350, 374 Weight Gain, 54, 374 Wheelchairs, 161, 374 White blood cell, 290, 294, 295, 301, 330, 332, 337, 338, 342, 349, 374 Windpipe, 348, 368, 374 Withdrawal, 154, 159, 168, 308, 374 Wound Healing, 123, 317, 334, 374 Wounds, Gunshot, 363, 374 X Xenograft, 289, 374 Xerostomia, 4, 238, 374

393

X-ray, 304, 318, 343, 355, 356, 359, 364, 374

Y Yeasts, 318, 348, 374

394


395

396


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