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

HEMORRHAGIC STROKE A 3-IN-1 MEDICAL REFERENCE Medical Dictionary Bibliography & Annotated Research Guide TO I NTERNET R...

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HEMORRHAGIC STROKE A 3-IN-1 MEDICAL REFERENCE Medical Dictionary Bibliography & Annotated Research Guide TO I NTERNET

R EFERENCES

HEMORRHAGIC STROKE 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., 1960Hemorrhagic Stroke: 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: 0-497-00529-8 1. Hemorrhagic Stroke-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 hemorrhagic stroke. 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 HEMORRHAGIC STROKE ........................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Hemorrhagic Stroke ...................................................................... 4 E-Journals: PubMed Central ....................................................................................................... 21 The National Library of Medicine: PubMed ................................................................................ 22 CHAPTER 2. NUTRITION AND HEMORRHAGIC STROKE ................................................................. 35 Overview...................................................................................................................................... 35 Finding Nutrition Studies on Hemorrhagic Stroke ..................................................................... 35 Federal Resources on Nutrition ................................................................................................... 36 Additional Web Resources ........................................................................................................... 37 CHAPTER 3. ALTERNATIVE MEDICINE AND HEMORRHAGIC STROKE ........................................... 39 Overview...................................................................................................................................... 39 National Center for Complementary and Alternative Medicine.................................................. 39 Additional Web Resources ........................................................................................................... 44 General References ....................................................................................................................... 46 CHAPTER 4. PATENTS ON HEMORRHAGIC STROKE........................................................................ 47 Overview...................................................................................................................................... 47 Patents on Hemorrhagic Stroke ................................................................................................... 47 Patent Applications on Hemorrhagic Stroke................................................................................ 49 Keeping Current .......................................................................................................................... 50 CHAPTER 5. PERIODICALS AND NEWS ON HEMORRHAGIC STROKE.............................................. 51 Overview...................................................................................................................................... 51 News Services and Press Releases................................................................................................ 51 Academic Periodicals covering Hemorrhagic Stroke.................................................................... 53 CHAPTER 6. RESEARCHING MEDICATIONS .................................................................................... 55 Overview...................................................................................................................................... 55 U.S. Pharmacopeia....................................................................................................................... 55 Commercial Databases ................................................................................................................. 56 APPENDIX A. PHYSICIAN RESOURCES ............................................................................................ 61 Overview...................................................................................................................................... 61 NIH Guidelines............................................................................................................................ 61 NIH Databases............................................................................................................................. 63 Other Commercial Databases....................................................................................................... 65 APPENDIX B. PATIENT RESOURCES ................................................................................................. 67 Overview...................................................................................................................................... 67 Patient Guideline Sources............................................................................................................ 67 Finding Associations.................................................................................................................... 69 APPENDIX C. FINDING MEDICAL LIBRARIES .................................................................................. 71 Overview...................................................................................................................................... 71 Preparation................................................................................................................................... 71 Finding a Local Medical Library.................................................................................................. 71 Medical Libraries in the U.S. and Canada ................................................................................... 71 ONLINE GLOSSARIES.................................................................................................................. 77 Online Dictionary Directories ..................................................................................................... 81 HEMORRHAGIC STROKE DICTIONARY............................................................................... 83 INDEX .............................................................................................................................................. 121

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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 hemorrhagic stroke 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 hemorrhagic stroke, 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 hemorrhagic stroke, 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 hemorrhagic stroke. 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 hemorrhagic stroke, 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 hemorrhagic stroke. 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 HEMORRHAGIC STROKE Overview In this chapter, we will show you how to locate peer-reviewed references and studies on hemorrhagic stroke.

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

Warning Issued on PPA Source: Healthy Weight Journal. 115(2):18. March/April 2001. Summary: The Food and Drug Administration (FDA) has issued a warning to remove phenylpropanolamine (PPA) from all diet and drug products. PPA is used in many over-the-counter weight loss products and in cough and cold medications. PPA increases the risk of hemorrhagic stroke, or bleeding into the brain. Yale University researchers found an increased risk of hemorrhagic stroke among women within 3 days of taking diet pills. FDA concludes that PPA is not safe for continued use, and although the risk of hemorrhagic stroke is low, use of these products does not warrant the increased risk.

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Preexisting Dementia in Stroke Patients: Baseline Frequency, Associated Factors, and Outcome Source: Stroke. 28(12): 2429-2436. December 1997. Summary: This journal article describes a study of the baseline frequency of dementia in stroke patients, associated factors, and outcomes. The participants were patients admitted to the acute stroke unit of the Lille University Hospital in Lille, France. A total of 202 patients with ischemic or hemorrhagic stroke, aged 42 to 101 years, were enrolled. The patients were assessed for preexisting dementia within 48 hours of stroke onset using a French translation of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Six months later, survivors underwent a battery of neuropsychological tests that assessed a range of cognitive functions, functional impairment, and psychiatric symptoms. Thirty-three patients had preexisting dementia according to the IQCODE; the dementia had been previously diagnosed in only one case. Logistic regression analysis revealed that female gender, a family history of dementia, leukoaraiosis, and cerebral atrophy were independently associated with preexisting dementia. All of the survivors with prestroke dementia met the criteria for dementia at the 6-month neuropsychological evaluation. The authors conclude that some patients with poststroke dementia may have had unrecognized preexisting dementia. 4 tables, 68 references.

Federally Funded Research on Hemorrhagic Stroke The U.S. Government supports a variety of research studies relating to hemorrhagic stroke. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to hemorrhagic stroke. 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 hemorrhagic stroke. The following is typical of the type of information found when searching the CRISP database for hemorrhagic stroke: •

Project Title: A MOUSE MODEL OF CEREBRAL CAVERNOUS MALFORMATIONS Principal Investigator & Institution: Plummer, Nicholas W.; Molecular Genetics and Microbiology; Duke University Durham, Nc 27710 Timing: Fiscal Year 2002; Project Start 01-DEC-2001 Summary: (Verbatim from the Applicant's Abstract) Cerebral cavernous malformations (CCM) are vascular abnormalities in the brain which cause migraines seizures, and hemorrhagic stroke. Recently, mutations in the RAP1A-interacting gene CCM1 (KRIT1)

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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).

Studies

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have been identified in dominant inherited CCM type1. We will develop an animal model of CCM by targeted mutation of the mouse Ccm1 gene. Insertion of a LacZ reporter gene in the Ccm1 locus will allow us to investigate the developmental and cellspecific expression pattern of CCm1. Using heterozygous mutant mice, we will test the "two-hit" hypothesis of lesion formation which predicts that the vascular malformation in heterozygous human patients are due to somatic mutation resulting in complete loss of CCM1 at the site of the lesion. The phenotype of homozygous mutant mice will illuminate unidentified functions of Ccm1 during vasculogenesis or development of other organs. Fibroblast cells cultured from mutant mice will be used to investigate the role of Ccm1 in cell proliferation a Rapla signaling pathways. These experiments will help to explain the formation of CCM in human patients and shed light on basic aspects of vascular morphology and development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: AGING BRAIN--CEREBROVASCULAR MECHANISM & AMYLOID BETA Principal Investigator & Institution: Zlokovic, Berislav V.; Professor and Associate Chair; Neurosurgery; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2002; Project Start 01-MAY-1999; Project End 30-APR-2004 Summary: This proposal represents investigators from the University of Southern California, Columbia University and State University of New York at Stony Brook Schools of Medicine who participate in a multi-disciplinary program on Cerebrovascular Mechanisms in the Aging Brain. The goal of the program is to advance current knowledge regarding the role of vasculature in the aging brain and major CNS disorders in elderly that predispose to cerebrovascular amyloidosis (e.g., Alzheimer's Disease and related amyloid-beta-peptide (Abeta) disorders, such as hereditary cerebral hemorrhage with amyloidosis Dutch type), Abeta-related vascular injury, brain damage and stroke. We will apply concepts and techniques developed in cerebrovascular biology, blood-brain barrier (BBB) and cerebrospinal fluid physiology, molecular biology, molecular genetics, transgene mice with age-dependent vascular risk factors, and tissues and cell cultures from patients diagnosed with AD. The program consists of five Research Projects and three Core resources. Project 1, Dr. Zlokovic will study the role of BBB and brain clearance in regulating Abeta concentrations in cerebral vessel wall and brain. Project the role of BBB and brain clearance in regulating Abeta concentrations in cerebral vessel wall and brain. Project 2, Dr. Van Nostrand will study Abeta production by cerebrovascular smooth muscle cells in relation to amyloidosis. Project, Dr. Stern will study the role of receptor for advanced glycation and end products in acute and chronic cerebrovascular perturbation caused by Abeta and strokerisk factors. Project 44, Drs. Schreiber and Zlokovic will delineate the roles of Abeta dn amyloid in vascular hemostasis in relation to ischemic or hemorrhagic stroke. Project 5, Drs. Kalra and Rhodin will study the role of Abeta in migration of monocytes across the BBB and vascular wall. Core A is the administrative facility. Core B, Dr. Mackic and Kim will provide animal and cell culture facility. Core C, Dr. Miller will provide neuropathologic analysis. The integrated and complementary scientific research projects will provide a molecular and therapeutic rationale to prevent accumulation of Abeta and formation of amyloid in cerebral blood vessels and brain, and counteract agedependent mechanisms responsible for abnormal vascular responses, injury and brain damage. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ANIMAL MODELS FOR CEREBRAL AMYLOID ANGIOPATHY Principal Investigator & Institution: Levy, Efrat; Nathan S. Kline Institute for Psych Res Psychiatric Research Orangeburg, Ny 10962 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 28-FEB-2007 Summary: A L68Q variant cystatin C forms the amyloid deposited in cerebral vessel walls of patients with hereditary cerebral hemorrhage with amyloidosis, Icelandic type. There are several indications that cystatin C also has a pathogenic role in Alzheimer's disease (AD), in cerebral amyloid angiopathy and in cerebral hemorrhage. A) Cystatin C colocalizes with amyloid beta in amyloid deposits in the brains of AD patients. The risk of cerebral hemorrhage increases in AD patients when high levels of cystatin C are present in cerebrovascular amyloid beta deposits. B) Cystatin C binds amyloid beta and its precursor and affects amyloid precursor protein processing. C) Both proteins accumulate in pyramidal neurons within the cerebral cortex. D) Recent genetic data suggest that the human cystatin C gene is a recessive risk gene for late-onset AD. We have generated lines of transgenic mice designed to provide disease models for cystatin C-cerebral amyloid angiopathy. High transgene expression was observed in the brain and plasma of these mice. Several aging transgenic mice overexpressing wild type or L68Q variant human cystatin C exhibited gross- or micro-hemorrhages but fibrillar amyloid deposits were not detectable in the brains of these mice. We hypothesize that accumulation of nonfibrillar cystatin C may contribute to hemorrhagic strokes. We propose to: 1) Characterize these transgenic mice, including: a) determination of cystatin C levels in the brains and peripheral tissues of young, mature, and aged mice; b) perform standard necropsies on a similar panel of mice, including immunostaining for cystatin C and amyloid deposition; c) seek evidence of macro- or micro-hemorrhages using appropriate staining techniques; 2) Study the mechanism by which high concentration of cystatin C causes hemorrhages: test the possibilities that cystatin C accumulation is toxic to vessel walls, alters coagulation and/or complement pathways, or both; and 3) Study the effect of cystatin C on amyloid beta deposition and cerebral hemorrhage in mice overexpressing human amyloid precursor protein, crossbred with cystatin C transgenic mice. The proposed animal models are crucial for understanding the etiology of cerebral amyloid angiopathy and hemorrhage and for the development of rational therapeutic interventions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BLOOD MARKERS OF ACUTE ISCHEMIC STROKE Principal Investigator & Institution: Sharp, Frank R.; Professor; University of Cincinnati 2624 Clifton Ave Cincinnati, Oh 45221 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: The diagnosis of cute stroke is based upon clinical findings and brain imaging. Blood markers of acute ischemic stroke or tPA-induced hemorrhage would be useful for initiating early treatment with tPA (tissue plasminogen activator) and related agents. This proposal will examine white blood cell RNA expression following ischemic compared to hemorrhagic stroke because microarray technology can survey thousands of RNAs at one time and because transcriptional responses can be rapid. Moreover, preliminary data in rodents shows a unique genomic response of white blood cells one day following ischemic stroke and hemorrhagic stroke when compared to each other and when compared to controls. This proposal will demonstrate the blood genomic changes at 24h following ischemic strokes and intracerebral hemorrhages in patients that do or do not receive tPA. The first aim will use human oligonucleotide arrays to

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examine the white blood cell genomic response at 24h after ischemic stroke, 24h after intracerebral hemorrhages, and in age, race and sex-matched control patients without neurological disease. We will show that there is a specific blood genomic profile that correlates with ischemic strokes compared to intracerebral hemorrhage and control patients; and that there is a blood genomic profile that correlates with intracerebral hemorrhages as compared to control and ischemic stroke patients. The second aim will use olgionucleo9tide microarrays to examine the blood genomic response at 24H in ischemic stroke patients that receive tPA+ eptifibatide by 3 hours. The blood genomic expression patterns in patients with tPA associated hemorrhages will be compared to those without hemorrhages as assessed by CT/MRI. One of the long-term goals as to identify, among the genes induced at 24h following an ischemic stroke in order to be able to diagnose ischemic cerebral events between 2 and 24h after the stroke using a blood test. Another long-term goal is to identify a set of genes in peripheral white blood cells at 2h after stroke that would be associated with tPA-associated intracerebral hemorrhages that might help guide the dose or decision to give thrombolytics. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CEREBRAL CONSUMPTION

MICROCIRCULATON

DURING

ALCOHOL

Principal Investigator & Institution: Mayhan, William G.; Professor; Physiology and Biophysics; University of Nebraska Medical Center Omaha, Ne 681987835 Timing: Fiscal Year 2002; Project Start 01-JAN-1999; Project End 31-DEC-2004 Summary: Chronic (heavy) consumption of alcohol has been recognized as a major contributing factor in the pathogenesis of many vascular diseases, including diseases of the brain. A large body of evidence suggests that chronic consumption of alcohol predisposes to the development of both hemorrhagic and thromboembolic stroke. Mechanisms by which chronic consumption of alcohol predispose to cerebrovascular abnormalities, including stroke, however, are not clear. The studies proposed in this application will determine the effects of chronic alcohol consumption on the cerebral microcirculation. The central hypothesis of this application is that chronic alcohol consumption predisposes to cerebrovascular abnormalities by altering cellular processes which modulate reactivity of cerebral blood vessels. To examine this central hypothesis, we will conduct two series of experiments. The first series of experiments will examine the temporal effect of chronic alcohol consumption on important cellular signaling pathways (nitric oxide synthase, ATP-sensitive potassium channels and adenylate cyclase which produce dilatation of cerebral arterioles. We will also determine the mechanisms which may account for impaired dilatation of cerebral arterioles during chronic alcohol consumption and examine the morphology of cerebral arterioles. The second series of experiments will examine the temporal effect of chronic alcohol consumption on the distribution of microvascular pressure in the cerebral circulation. We will examine the distribution of cerebral microvascular pressure under basal conditions and during changes in arterial pressure. We believe that these studies will provide the first comprehensive examination of the effects of chronic alcohol consumption on the cerebral microcirculation and will provide valuable insights into factors which contribute to the pathogenesis of cerebrovascular abnormalities, possibly ischemic and hemorrhagic stroke, during chronic alcohol consumption. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CEREBRAL MICROVASCULAR ENDOTHELIN PRODUCTION Principal Investigator & Institution: Yakubu, Momoh A.; Ctr/Cardiovascular Diseases; Texas Southern University 3201 Wheeler Ave Houston, Tx 77004 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 29-SEP-2004 Summary: (provided by the applicant): Cerebral hemorrhage is the main cause of abnormal cerebral arteriolar constriction resulting in cerebral ischemia that leads to paralysis, mental and physical disabilities, and deaths. Despite progress in the diagnosis of subarachnoid hemorrhage (SAH), SAH-induced cerebral vasospasm remains one of treatable causes of morbidity and mortality in patients. The mechanism(s) by which cerebral arterial narrowing occurs following hemorrhage remain largely unknown, but modification of cerebral microvascular responses is prominent, and characterized by impaired vasodilator and increased vasoconstrictor mechanisms in cerebral arteries. Several factors may contribute to the observed alterations of pial arteriolar reactivity. Increased endothelin-1 (ET-1) production has been consistently observed and ET-1 has been implicated as a possible mediator of cerebral hemorrhage-induced vasospasm. However, the mechanism(s) by which increased ET-1 production occurs are not known. The proposed experiments are designed to test the hypothesis that by-products of hemolyzed blood clots {oxyhemoglobin (OxyHb), lysophosphatidic acid (LPA), or serotonin (5-HT)} stimulate ET-1 production via activation of protein kinase C (PKC). To test this hypothesis, two specific aims will be addressed using primary culture of cerebral microvascular endothelial cells. 1) To characterize the effects of OxyHb, LPA, or 5-HT on El-I production and 2) to determine the cellular mechanism(s) by which these vasospasmogenic agents released from blood clots stimulate El-I production. To accomplish these aims, primary cell culture, molecular biological, immunoblotting, and immunoprecipitation techniques will be employed to investigate the mechanism(s) involved in the regulation of ET-1 production by these blood by-products. The results from the proposed research will have important therapeutic implications for survivors of SAH, who experience complications that include paralysis, mental and physical derangement, loss of sight and hearing. Our understanding of the mechanisms underlying the consequences of SAH will make it possible for early and appropriate intervention to prevent or reduce these complications from hemorrhagic stroke. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CONSTRAINT INDUCED MOVEMENT THERAPY IN SUBACUTE STROKE Principal Investigator & Institution: Grotta, James C.; Professor; University of Texas Hlth Sci Ctr Houston Box 20036 Houston, Tx 77225 Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 31-AUG-2007 Summary: (provided by the applicant): SPECIFIC AIMS: 1. Evaluate the effects of two weeks of treatment with Constraint Induced Movement therapy (CIMT) combined with behavioral training of the paretic upper limb on motor recovery in patients with ischemic or hemorrhagic stroke who are initially treated within 14 days poststroke. 2. Investigate reorganization of cortical motor representation using transcranial magnetic stimulation (TMS) after two weeks of combined CIMT and behavioral training of the paretic upper limb in patients who begin treatment within 14 days after onset of ischemic or hemorrhagic stroke. 3. Using transcranial magnetic stimulation, investigate the relationship between changes in cortical representation and improvement in motor function of the affected upper limb in patients treated within 14 days after sustaining ischemic or hemorrhagic stroke. HYPOTHESES: 1. CIMT given daily for two weeks

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concomitant with behavioral training of the affected upper limb facilitates motor recovery relative to an equal number of sessions of traditional therapy in patients who are initially treated by day 14 after ischemic or hemorrhagic stroke. 2. Combined CIMT and behavioral training of the affected upper limb administered daily for 2 weeks beginning by day 14 post-stroke will increase cortical representation of the affected hand as measured by TMS. 3. Improved motor function of the affected upper limb will be related to the post treatment increase in cortical representation on TMS. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CORE--BLOOD AND TISSUE SPECIMEN Principal Investigator & Institution: Vinters, Harry V.; Professor and Chief; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-MAY-2008 Summary: (provided by the applicant): This Core will serve as a vital resource center for blood and tissue-based studies integral to the completion of investigational projects, related to aggressive, interventional treatment of cerebral hemorrhage and ischemic infarcts. It will bring to analyses of blood and tissues derived from study patients a wealth of expertise in morphoanatomical techniques pertinent to stroke pathogenesis, and provide access to key investigators of samples of brain tissue derived from biopsy and autopsy specimens of study patients. The core will support Project 1, the MR RESCUE trial, in which intravascular thrombus material will be removed in the course of therapeutic thrombectomy. The core will assist investigators studying the biochemical pathogenesis of thrombus formation, and its possible importance in evolution of cerebral infarcts, and will assist investigators in correlating their findings with light microscopic/ultrastructural features of the thrombi. The core will also provide support to Project 2, the HEME Surgery trial, in which brain tissue originating from 'clot' evacuations carried out in patients with spontaneous intracerebral (parenchymal) hemorrhage will be carefully evaluated for both the likely etiology of hemorrhage and the tissue response to intracerebral blood, and readied for studies of differential gene expression employing qualitative, real-time RT-PCR and cDNA arrays. The Core will store blood samples from appropriate patients for DNA analysis, and provide these to researchers following appropriate review of their investigational goals and projects. The Core will serve as an important 'blood and brain tissue' resource to SPOTRIAS investigators at UCLA, and a larger network of investigators with interests in the treatment of acute ischemic and hemorrhagic stroke. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DIETARY PATTERNS AND RISK OF CARDIOVASCULAR DISEASE Principal Investigator & Institution: Hu, Frank B.; Nutrition; Harvard University (Sch of Public Hlth) Public Health Campus Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 01-AUG-1998; Project End 31-JAN-2005 Summary: This new application presents plans to study, prospectively, the association between dietary patterns and risk of coronary heart disease (CHD), ischemic stroke, and hemorrhagic stroke in cohort studies of 121,700 women age 30 to 55 years at baseline in 1976 (the Nurses; Health Study; NHS) and 51,529 men aged 40-75 years at baseline in 1986 (the Health Professionals Follow-up Study; HPFS). Food consumption data were collected through semiquantitative food frequency questionnaires at baseline and during follow-up in each of the cohorts. Dietary patterns are derived from the food consumption data using factor analysis, cluster analysis, and dietary indexes (based on

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prevailing dietary recommendations). In addition, using existing datasets from dietary validation studies in sub-samples of the two cohorts, the investigators propos to evaluate the reproducibility and validity of dietary patterns defined by factor/cluster analysis and dietary indexes. Further, using prospectively collected and stored bloods in the NHS (n-32, 826) during 1989-1990 and the HPFS (n-18, 000) during 1993-1994, we propose to examine whether observed associations between dietary patterns and CHD are explained by (or mediated through) plasma biochemical measurements (including serum lipids, thrombotic factors, antioxidants, fasting insulin, and homocysteine levels) in a nested case-control design; and they propose to assess prospectively the relationship between dietary patterns and these biomarkers in the control samples. The funded NHS and HPFS will provide follow-up and documentation of CHD and stroke in addition to covariate information. Assays of biomarkers in the two cohorts are funded through other grants. Overall, the large size of these cohorts, the prospective design, the high follow-up rates, and the availability of archived blood specimens provide a unique opportunity to study the relationship between overall dietary patterns and cardiovascular disease in an extremely cost-efficient manner. This would be the first study to characterize dietary patterns in large cohorts of men and women and relate dietary patterns to CHD and stroke. Finally, this project will enable evaluation of prevailing dietary recommendations in relation to both biomarkers of risk as well as clinical cardiovascular diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENE MALFORMATIONS

DISCOVERY

FOR

CEREBRAL

CAVERNOUS

Principal Investigator & Institution: Marchuk, Douglas A.; Associate Professor; Molecular Genetics and Microbiology; Duke University Durham, Nc 27710 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2007 Summary: (provided by the applicant): Cerebral cavernous malformations (CCMs) of the brain are vascular lesions, which are present in up to 0.4% of the general population and often are accompanied by seizures, migraine, hemorrhagic stroke and other neurological outcomes. These lesions can occur sporadically, or as an autosomal dominant trait. Our group has recently identified the CCM1 gene, which is responsible for the majority of all familial CCMs and principally the cause for the familial form of CCMs in the Hispanic population (Sahoo et al., 1999). With the discovery of the CCM1 gene, we have developed a significant insight into the pathology of this "familial stroke." There are two additional CCM genes that remain to be identified, CCM2 on chromosome 7p and CCM3 on chromosome 3q. We will utilize our previously successful approach for positional cloning, which employs a strong computational approach to transcript identification in order to identify positional candidates for sequencing. We believe that the resources will have accumulated and the approach we have established will allow us to identify the genes for CCM2 and CCM3. After identifying the genes responsible for CCM2 and CCM3, we will begin to investigate their role in the cell, and in particular, their role in the pathophysiology of CCM. These types of experiments include overall protein expression patterns in the embryo and the adult, cellular compartment localization studies, and a search for interacting proteins using the yeast two-hybrid screen. These data will provide the molecular/cellular framework from which to launch a more detailed analysis of these proteins in a future proposal. Our ultimate objective is to aid in understanding the fundamental mechanisms responsible for different forms of familial neurovascular disease. The availability of a model, where the primary genetic determinates have been identified

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unambiguously, will greatly expedite the search for the basic mechanisms involved in "familial stroke" and to a better understanding of neurovascular disease, in general. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HELICOPTER TRANSPORT AND OUTCOME IN HEMORRHAGIC STROKE Principal Investigator & Institution: Bear, Taylor C.; Akron General Medical Center 400 Wabash Ave Akron, Oh 44307 Timing: Fiscal Year 2003; Project Start 01-SEP-2003 Summary: (provided by applicant): Since its introduction into civilian medicine in the early 1970's, the helicopter has made significant improvements in the care of patients, particularly in rural or isolated areas. The benefit and improved outcomes have been largely demonstrated in victims of trauma or patients suffering acute myocardial infarction. The role of aeromedical transport in non-traumatic hemorrhagic stroke is unknown. This is a retrospective, multi-center, cohort study designed to evaluate the outcome, interventions, and procedural care after helicopter transport in non-traumatic hemorrhagic stroke. Study groups include helicopter-transported (HT) patients with SAH or sICH, which will be compared with non-helicopter-transported (NHT) patients with SAil or sICH. Helicopter-transported patients are selected from a recently completed database of stroke patients transported by on helicopter program. HT and NHT patients will be matched on appropriate socio-demographic variables and diseasespecific indices including GCS grade scores and location of hemorrhage in sICH patients. Charts will be reviewed for TISS scores, hospital procedures, and DNR status. Thirty-day mortality will be determined using the social security death index and state death records. Estimated sample size is 400 patients. Primary endpoint is to determine mortality between HT and NHT patients. Additional endpoints include study of TISS scores, number and type of procedures and the role of DNR in these two patient groups. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: INFLAMMATION MARKERS OVER TIME IN CARDIOVASCULAR DISEASE Principal Investigator & Institution: Tracy, Russell P.; Professor; Pathology; University of Vermont & St Agric College 340 Waterman Building Burlington, Vt 05405 Timing: Fiscal Year 2002; Project Start 13-APR-1992; Project End 30-NOV-2003 Summary: The majority of myocardial infarction and stroke events occur in those over the age of 65. We have demonstrated during the previous grant period that measures of subclinical cardiovascular disease (CVD) and markers of inflammation and blood clotting are powerful risk factors for clinical CVD, myocardial infarction (MI) and CHD death in individuals aged 65+. We believe that measurements of these factors in proximity to the event, together with measures of subclinical disease, will significantly improve the identification of those older individuals most likely to have a clinical CVD event. We have three specific aims: 1) to measure markers of inflammation, such as fibrinogen, C-reactive protein, and ICAM-1 in sequential samples from the Cardiovascular Health Study, representing years 2, 5, 6, 7, 9, 10 of the study; 2) to measure in the same way selected cytokines and cytokine-related factors, such as IL-6, IL-1b and soluble IL-2 receptor; and 3) to measure in the same way markers of hemostatic and fibrinolytic activation, such as factor V/Va. Plasmin-a2 Anti-plasmin Complex, and D-dimer. We will evaluate each of the chosen markers as a risk factor for three outcomes: incident coronary heart disease (CHD) including fatal and non-fatal

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Hemorrhagic Stroke

non-hemorrhagic stroke; and incident cancer of the breast, lung, colon and prostate. With these data we will test two major hypotheses: 1) prediction of events is stronger when measurements are done closer in time ( 1 year); and 2) changes in the levels of markers over time (e.g., between baseline and the most proximate measure, or between the two most proximate measures) will be better predictors of events than a single measurement. We believe that markers will be more closely associated with MI and CHD death than with other manifestations of atherosclerotic disease such as stroke. Since there is growing evidence that inflammatory markers are related to risk of cancer, the cancer comparison group will provide information as to the specificity of these markers for CHD. It is likely our results will have important implications for prevention, diagnosis, and future therapeutic interventions in cardiovascular disease in the elderly. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MELANOCORTIN SIGNALING IN HYPERTENSION Principal Investigator & Institution: Wachira, James; Morgan State University Baltimore, Md 21251 Timing: Fiscal Year 2003; Project Start 01-MAR-2003; Project End 28-FEB-2007 Summary: The long-term objectives of this study are to better understand the role of the brain in hypertension. Hypertension is a major contributor to health disparity among minorities and a major cause for both ischemic or hemorrhagic strokes and chronic brain injury. Currently, the causes for most cases of essential hypertension as well as changes in brain signal tranduction pathways during hypertension are not well understood. However, an aberration in neural blood-pressure control mechanisms is known to be necessary for the persistence of raised blood pressure. Melanocortins have been implicated in autonomic control of blood pressure with gamma-2-MSH demonstrating the highest potency in increasing blood pressure and heart rate. Previous studies have also demonstrated an increase in intracellular Ca2+ and protein kinase C (PKC) translocation in rat brain-stem synaptosomes treated with gamma-2-MSH. Modulation of the PKC signaling pathway by gamma-2-MSH was also observed in a brain-stem neuronal cell line transfected with a neural melanocortin receptor, MC3-R. This study will test the hypothesis that melanocortins function in autonomic neurons by modulating signal transduction systems that are coupled to specific neurotransmitter systems. The first aim is to identify changes in neural melanocortin signal transduction in stroke-prone spontaneous hypertensive rat (SHR-SP) brain. Hypothalamus and brain stem slices from SHR-SP and control Wistar Kyoto (WKY) rats will be treated with melanocortins in the presence of agonists for putative melanocortin-sensitive neurotransmitter systems (adrenergic, serotonergic and dopaminergic) and the phosphorylation patterns of total proteins and specific signal transduction components analyzed. Secondly, changes in second messenger molecules will be assayed using ELISA/RIA procedures. The second aim will seek to characterize signaling through the melanocortin 3-receptor (MC3-R) in vitro. Similar studies will be performed in MC3-R trasfected neuronal cells, followed by the analysis of expression and activation of protein kinase A (PKA), protein kinase B (PKB) and PKC SerFFhr kinases, upon treatment with gamma-2- MSH. This study will therefore provide important insights into the role and mechanism of neural melanocortin signaling system in autonomic functions and also identify neural signal transduction cascades that play a potential role in hypertension. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MR ASSESSMENT OF MAGNESIUM IN ACUTE STROKE Principal Investigator & Institution: Kidwell, Stella M.; Assistant Clinical Professor; Neurology; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 02-APR-1999; Project End 31-MAR-2004 Summary: The objectives of this project are to demonstrate that 1) intravenous magnesium is beneficial in acute ischemic stroke as evidenced by decrease in the growth of infarct volume over time as measured by diffusion weighted magnetic resonance imaging (DWI); 2) DWI is a valuable surrogate outcome measure in acute ischemic stroke clinical trials; 3) diffusion/perfusion mismatch is a useful entry criterion for neuroprotective treatment in acute stroke clinical trials; and 4) intravenous magnesium is safe and potentially beneficial in intracerebral hemorrhage. During the first phase of the project, objectives 1-3 will be assessed by conducting a randomized, double-blind, placebo controlled trial to evaluate the efficacy of intravenous magnesium as a neuroprotective agent in acute ischemic stroke. The trial will use diffusion/perfusion magnetic resonance imaging as a surrogate outcome marker. 150 patients will be enrolled within 12 hours of symptom onset at 3 UCLA-associated hospitals. The second phase of this project will be a parallel pilot randomized, double-blind, placebocontrolled trial to evaluate the safety and explore the efficacy of intravenous magnesium in acute intracerebral hemorrhage, enrolling 40 patients. Additional data will be collected to assess the diffusion/perfusion MR signature of acute intracerebral hemorrhage. The findings of this project will have direct relevance to future treatment of acute ischemic and hemorrhagic stroke as well as to the design of future trials of neuroprotective agents. The results will help establish the utility of novel diffusion/perfusion MR techniques as demonstrating physiologic, objective changes that can be used as entry and outcome criteria in evaluating stroke patients. During the award period, in addition to serving as the principal investigator of these trials, Dr. Kidwell will pursue in-depth didactic multidisciplinary training in biostatistics, epidemiology, clinimetrics and magnetic resonance radiology. She will be mentored by Drs. Jeffrey Saver, Sidney Starkman, Jeffry Alger, and Barbara Vickrey. At the completion of this training, Dr. Kidwell will have acquired all requisite experience and skills to function as an independent investigator in clinical studies of novel magnetic resonance stroke imaging techniques, pivotal trials of promising therapeutic agents, and studies of the pathophysiology of acute human cerebral ischemia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NC-758 HEMORRHAGE

FOR

PREVENTION

OF

RECURRENT

CEREBRAL

Principal Investigator & Institution: Greenberg, Steven M.; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-JAN-2006 Summary: (provided by the applicant): There is no known therapy for Cerebral Amyloid Angiopathy (CAA), an important cause of hemorrhagic stroke and other clinical syndromes in the elderly. The pathologic basis of CAA-related stroke is deposition of the Amyloid B-peptide (AB) in cerebral vessels, and resultant degeneration of the vessel wall. We propose a multi-center, phase II pilot study of the safety, tolerability, and preliminary efficacy of NC-758 for secondary prevention of recurrent CAA-related intracerebral hemorrhage. NC-758 is a small molecule designed to compete with glycosaminoglycans for binding to AB. Preliminary studies have

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Hemorrhagic Stroke

demonstrated that this compound penetrates to the CNS, inhibits AB fibril formation and AB-induced cellular toxicity, and reduces severity of CAA in a transgenic mouse model without evidence for major intrinsic toxicity. The proposed trial builds on progress by the Principal Investigator in the diagnosis and staging of CAA. Participants will be survivors of lobar hemorrhagic stroke, considered at high-risk for recurrence based on baseline gradient-echo MRI scan, or apolipoprotein-E genotype. An anticipated 280 patients will be screened at 20 participating sites, and 210 patients randomized to receive low-dose NC-758, high-dose NC-758, or placebo. Patients will be treated for a 16-month period, and followed for adverse clinical events, laboratory abnormalities, and recurrent stroke or decline in cognitive, functional, or neurologic status. At 8 and 16 months of treatment, subjects will undergo follow-up MRI scans to determine the appearance of new hemorrhagic lesions during treatment. The proposed sample size is calculated to have high likelihood of detecting major adverse effects associated with NC-758, and for detecting a 50% reduction in appearance of new symptomatic and asymptomatic hemorrhages. In addition to testing a promising agent for CAA, the proposed study will generate the organization and pilot data to serve as a springboard for future trials of emerging anti-amyloid treatments. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEW POLYMER CEREBRAL ANEURYSM FILLER DEVICE Principal Investigator & Institution: Lee, Jeffrey A.; Neurovasx, Inc. 2355 Polaris Ln N, Ste 116 Plymouth, Mn 55447 Timing: Fiscal Year 2003; Project Start 30-SEP-2001; Project End 30-NOV-2004 Summary: (provided by applicant): Hemorrhagic stroke following aneurysmal rupture represents 15% to 30% of all strokes, with greater than 40,000 deaths per year attributed to acute aneurysmal rupture in the United States alone. Additionally, another 28,000 to 36,000 acutely ruptured aneurysms are treated per year in the U.S. The incidence of an intracranial aneurysm in the general population has been estimated to be between 1.5% to 8%. Current treatment options for cerebral aneurysm fall into two categories: surgical and interventional. Surgical procedures involve a long, delicate operation that has significant risk and a long period of postoperative rehabilitation and critical care. Recently, with the advent of neuro-interventional devices such as the Guglielmi detachable platinum coils (GDCs), a new endovascular modality for the treatment of cerebral aneurysms has become available. Our goal is to develop an endovascularly placed polymer aneurysm filler technology for treatment of aneurysms that is designed to address the shortcomings of interventional aneurysm treatment with platinum coils. We are developing a polymer filler material to be delivered in much the same way that a meallic coil is implanted. We anticipate that a packing density of at least 70% can be achieved. This substantially greater filling capability combined with the polymeric surface and surface-coating technologies will allow for permanent healing at the neck of the aneurysm. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NON-INVASIVE PNEUMOTHORAX DETECTOR Principal Investigator & Institution: Kelsch, Daniel N.; Engineering Program Mgr; Biomec, Inc. 1771 E 30Th St Cleveland, Oh 441144407 Timing: Fiscal Year 2003; Project Start 30-SEP-2000; Project End 30-APR-2005 Summary: Pneumothorax, while easily treatable, can become life threatening if not detected at any early stage. Current methods for diagnosing pneumothorax (chest x-ray,

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chest CT scan) are not possible for emergency squads and not practical for long-term monitoring of critical care patients. A portable handheld pneumothorax detector that is inexpensive, accurate, and non-invasive therefore would be very attractive. In Phase I, we investigated the feasibility of such a device, based on micropower impulse radar (MIR) technology. In animal studies (swine model), we are determined that pneumothorax as small as 30 ml were clearly detectable by the MIR device. This level of detection is important for the feasibility, since it is below the threshold of clinical significance. In Phase II, we propose to further optimize the MIR characteristics of the device and the signal algorithms. We will then acquire scans on human subjects to confirm the correlation of the MIR measure to the chest x-ray, which is the present standard of care. After finalizing the device parameters, we will continue with device development, miniaturization, and packaging. This research will result in a design ready for commercialization that fulfills the need for a non- invasive pneumothorax detector. PROPOSED COMMERCIAL APPLICATIONS: A handheld inexpensive pneumothorax will be commercially attractive to emergency medical personnel and trauma clinicians. Also, it would be useful for patient monitoring in critical care units. The combined market for these applications if very large. With further development, the device may be tunable to detect other trauma conditions, such as hemotoma and hemorrhagic stroke. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OPTICAL COHERENCE DOMAIN REFLECTOMETRY IN BRAIN PROBES Principal Investigator & Institution: Huang, David; Surgery; Cleveland Clinic Lerner Col/Med-Cwru Cleveland, Oh 44195 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): The goal of this project is to develop optical coherence domain reflectometry (OCDR) for accurate image guided placement of treatment probes in deep-brain structures. Refined guidance would greatly enhance the effectiveness and safety of deep-brain stimulation (DBS) with implanted electrodes. DBS is an FDA-approved treatment for Parkinson's disease and essential tremor that provides long-term relief of symptoms when medications are inadequate. It is also a promising therapy for intractable dystonia, epilepsy, and obsessive-compulsive disorder. Although effective, DBS is not currently a first-line treatment because of difficulties with precise placement, as well as risks of causing hemorrhagic stroke and other complications. Moreover, lengthy intraoperative electrical recordings and stimulus-response observations are currently required to position the probe. An embedded OCDR sensor may provide information on brain structures several millimeters ahead of the probe tip, enabling more precise, rapid, and safe placement. These improvements would allow DBS to benefit more patients. OCDR-guided deepbrain probes could also provide precise delivery of therapeutic vehicles in gene therapy, neurotransplantation, neuro-ablation, and pharmacologic treatments. The investigators include an original developer of OCDR and optical coherence tomography (OCT) in biomedical applications and an expert practitioner and developer of the DBS technique. The combined expertise of this team will take several promising approaches to using OCDR to identify brain tissue types (cortex, tracts, nuclei, and blood vessels) through a miniature probe. The following Specific Aims are proposed: Aim 1: Develop a combined OCDR/microelectrode brain probe. Aim 2: Distinguish brain tissue types using a dualwavelength OCDR system that measures tissue reflectivity, attenuation, hydration, and birefringence. Aim 3: Detect blood vessels by Doppler shift and broadening of OCDR

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Hemorrhagic Stroke

spectrum. Aim 4: Develop analysis & display software to identify tissues and guide probe advance. The OCDR brain probe technology will be validated in the laboratory and tested in a rat model. The practical knowledge gained in this pilot project will be used to develop a clinical OCDR-guided deep-brain probe for human DBS studies. Successful completion of this project would greatly benefit patients with many neurologic and psychiatric disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PORTABLE NON-INVASIVE ACOUSTIC IDENTIFICATION OF STROKE Principal Investigator & Institution: Sewell, John M.; Active Signal Technologies, Inc. 13025 Beaver Dam Rd Cockeysville, Md 21030 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-AUG-2004 Summary: (provided by applicant): Active Signal Technologies, in partnership with the Brain Attack Team of the University of Maryland Medical Center, proposes to refine and test a novel portable, non-invasive system that will enable rapid identification of stroke. Approximately 750,000 people suffer a stroke each year and over 80% of these are ischemic. Yet only 1% of this number receives medical treatment such as TPA that is known to dissolve clots and promote favorable outcome if administered within 3 hours of onset. Among the many causes of this serious health and ultimately economic problem is the inability to rapidly differentiate ischemic from hemorrhagic strokes to allow intervention. The device is a small non-invasive system that measures the acoustic signature of the brain and compares it with the patient's arterial waveform. Active Signal will add code to calculate those signal features identified in Phase I as indicative of the patient's stroke condition, and the team will clinically test on 200 patients the hypotheses for stroke identification determined in Phase I. The system will be miniaturized for EMS units to use at the scene of injury. This would significantly increase the percentage of ischemic stroke patients who would receive time-sensitive therapies, reducing disability and medical costs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: THE RELATIONSHIP OF SERUM PROTEINS TO STROKE SEVERITY Principal Investigator & Institution: Jauch, Edward C.; Asst. Professor; University of Cincinnati 2624 Clifton Ave Cincinnati, Oh 45221 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: The approval of tissue plasminogen activator (tPA) for use in acute ischemic stroke by the FDA in 1996 dramatically changed the treatment of stroke. Yet, many patients who are potential candidates do not receive thrombolytics due to the treating physician's concern of hemorrhage. New diagnostic tests to identify patients at increased risk of tPA-associated hemorrhage, to predict long-term outcome, and to measure therapeutic efficacy would ve very useful to physicians who treat acute stroke patients with tPA or other therapies. This proposal will examine the relationship of serum proteins to baseline stroke severity, clinical and radiographic outcome, response to therapy, and the risk of intracerebral hemorrhage after tPA+/- eptifibatide therapy in the CLEAR Trial. In Aim 1, based on our preliminary findings, two serum proteins, S100 and myelin basic protein (MBP), will be studied over the first 24 hours from presentation. Changes and peaks in S100 and MBP concentrations will be correlated with the severity of neurologic deficit, volume of infarct on CT and magnetic resonance imaging, flow in the middle cerebral artery as measured by magnetic resonance

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angiography, presence of intracerebral hemorrhage, and long-term outcome. Aim 2 will employ a proteomics approach to identify plasma proteins that are associated with intracerebral hemorrhage following administration of tPA. Pretreatment plasma from patients who do not develop intracerebral hemorrhage. A long-term goal of this study is to develop serum marker assays as independent measures of prognosis and therapeutic efficacy. Such tools would be useful in the design of new clinical therapeutic trials and the selection of therapies in acute stroke. Long-term goals associated with the proteomics study include developing rapid assays that could be used to identify patients at increased risk of hemorrhage to better select patients for thrombolytic therapy. Additionally, the protein library created by this project could help identify new proteins associated with ischemic stroke leading to improved diagnostic assays with increased sensitivity, specificity, and accuracy for cerebral ischemia. Overall, this project in conjunction with Project 3, represents a unique opportunity to compare both a proteomics and genomics approach in a single disease condition, thereby complementing each strategy's strengths. We expect this project will lead to the development of further proteomics and genomics studies of ischemic and hemorrhagic stroke. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THE ROLE OF ZINC IN FOCAL ISCHEMIC BRAIN INJURY Principal Investigator & Institution: Lee, Jin-Moo; Neurology; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2003; Project Start 25-SEP-2000; Project End 31-JUL-2005 Summary: (provided by applicant): This is an application for a competitive supplement to the three-year Mentored Clinical Scientist Development (K08) Award. The original K08 grant entitled, "The role of zinc in focal ischemic brain injury," was awarded on 7/1/00. However, in 12/01 (1.5 years into the grant), the applicant's mentor, Dr. Dennis Choi left the institution, prompting a change in mentors (to Dr. Chung Y. Hsu, with comentors, Dr. Mark Goldberg and Dr. David Holtzman) and a change in research direction. For the past 9 months, the applicant has been pursuing this new direction, studying the pathogenesis of spontaneous intracerebral hemorrhage in cerebral amyloid angiopathy (CAA). In particular, he has found that the amyloid beta peptide induces the expression and activity of the extracellular matrix-degrading protease, matrix metalloproteinase-9 (MMP-9), in cultures of cerebral endothelial cells. Furthermore, vascular MMP-9-like immunoreactivity was found in aged mice carrying the double Swedish mutation of the amyloid precursor protein (APPsw, a rodent model of CAA), but not in younger mice. The central hypothesis of this proposal is that amyloid beta, which accumulates in cerebral blood vessels in CAA, induces vascular MMP-9 activity and contributes to the development of spontaneous hemorrhagic stroke. Due to space limitations a complete application detailing the new proposal is not possible; however, Specific Aims, preliminary studies, and a brief outline of research design is included in this proposal. The goal of the applicant during this extension is to pursue the project outlined above and to receive additional training in molecular biology, microscopy and in developing animal models for disease. The additional two years of funding will allow protected time to accumulate data and publications that will put the applicant in a position to apply for independent funding (R21 or R01) and, ultimately, develop into an independent investigator. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TISSUE VIABILITY IN STROKE BY SODIUM MR IMAGING Principal Investigator & Institution: Thulborn, Keith R.; Professor of Medicine; Radiology; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2003; Project Start 20-APR-2000; Project End 31-JAN-2005 Summary: Tissue sodium concentration (TSC), as measured by sodium imaging, will be correlated with diffusion (apparent diffusion coefficient, ADC) and perfusion (relative cerebral blood volume, rCBV; tissue transit time, TTT; arrival time, TA) from proton MRI over the first 12 hours of embolic stroke in a non-human primate model. These quantitative MR imaging parameters will be correlated with histological markers of tissue status including TTC, H&E and TUNEL staining. The goal is to establish if TSC an be used as a measure of tissue viability in assessment of acute stroke. Early intervention with thrombolysis enhances the clinical outcome if the tissue is still viable. As reperfusion of infarcted tissue increases the risk of adverse hemorrhage, the FDA approves a limited window of acceptable risk-benefit ratio of 3 hours from the onset of neurological symptoms in a non-hemorrhagic stroke. A rapid method for assessment of tissue viability in this setting would aid in tailoring clinical management to the pathophysiology of each patient. The central hypothesis is that there is a critical increase in TSC due to loss of sodium ion homeostasis in a region of restricted diffusion (reduced ADC) that indicates a significant loss of tissue viability in stroke. An acute embolic stroke model in a non-human primate is used to determine if a critical threshold of TSC defines tissue viability during the natural progression of stroke thereby predicting recovery following reperfusion after thrombolysis with recombinant tissue plasminogen activator (rt-PA) This animal model is required to establish the magnitude and rate of change of TSC in a well-controlled setting that can be applied in the clinical setting. Other proton MRI parameters used clinically in stroke are water diffusion and perfusion. The same comprehensive, yet efficient MRI protocol as I have used in MRI examinations of both acute and sub-acute stroke patients, allows TSC, ADC and blood pool perfusion parameters or rCBV, TTT and TA to be correlated in this acute stroke model and compared to histological parameters of necrosis and apoptosis. The novel twisted projection imaging acquisition produces high quality, high-resolution sodium images while echo-planar imaging is used for diffusion and perfusion imaging. A dualfrequency, dual-quadrature, 23NA/1H RF coil ensures co-registration of images and maps in minimum time without moving the subject. This well-controlled animal model examines if there is a critical TSC threshold that accurately predicts tissue viability as part of this comprehensive MR imaging protocol being used for clinical management of acute stroke. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TRANSGENIC MODEL FOR CEREBRAL AMYLOID ANGIOPATHY Principal Investigator & Institution: Van Nostrand, William E.; Professor; Medicine; State University New York Stony Brook Stony Brook, Ny 11794 Timing: Fiscal Year 2002; Project Start 01-MAY-1998; Project End 31-JUL-2007 Summary: (provided by applicant): Cerebrovascular deposition of the amyloid a-protein (Aa), a condition known as cerebral amyloid angiopathy (CAA), is a common pathological feature of patients with Alzheimer's disease (AD) and several related hereditary cerebral hemorrhage with amyloidosis (HCHWA) disorders. Aa is proteolytically derived from its parent molecule the amyloid a-protein precursor (AaPP). Apolipoprotein E (ApoE) genotype can facilitate both cerebrovascular Aa deposition and hemorrhagic stroke. It is significant that CAA accounts for up to 20% of

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cases of spontaneous primary intracerebral hemorrhage. Moreover, CAA is most severe in HCHWA patients often resulting in early recurrent and fatal intracerebral hemorrhages. The reason as to why there is preferential cerebrovascular Aa deposition in HCHWA disorders leading to hemorrhagic stroke and how ApoE may facilitate these pathological processes remains unresolved. We have shown that certain HCHWA mutant forms of Aa, which exhibit a loss or change in charge at peptide residues 22 or 23, possess enhanced pathogenic properties towards cultured cerebrovascular cells. In addition, ApoE genotype can further influence the pathogenic effects of Aa in these in vitro paradigms. However, many of these issues can be better studied in valid in vivo models for CAA. Therefore, the overall hypotheses that forms the basis of this proposal is that expression of HCHWA mutant AaPP in transgenic mice will lead to the preferential development of CAA and human ApoE genotype can further influence this pathology and promote cerebral hemorrhage. The broad objectives of this proposal are two-fold. First, we will compare the pathological consequences of neuronal overexpression of several human AaPP forms yielding either wild-type or CAA mutant Aa with regards to the development of CAA. The CAA mutant forms AaPP will contain either a single Dutch E22Q AB substitution or double Dutch/Iowa E22Q,D23N Aa substitutions. Second, the influence of human ApoE genotype on Aa deposition, the development of CAA, and cerebral hemorrhage will be investigated in these in vivo models. These proposed studies stem from our overall focus and continuing work on investigating the role of ABPP and its derived fragment A6 in the development of CAA, loss of vessel wall integrity, and hemorrhagic stroke. Completion of these specific aims will produce valuable models for both the further study of pathogenic mechanisms in CAA and in vivo systems to develop and test therapeutic strategies to mitigate cerebrovascular Aa deposition and the subsequent pathological consequence of hemorrhagic stroke. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: UCLA SPOTRIAS CENTER APPLICATION Principal Investigator & Institution: Saver, Jeffrey L.; Neurology; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-MAY-2008 Summary: Acute stroke is a common and devastating disorder, the 3rd leading cause of death and the leading cause of adult disability in the US. This application to establish a Specialized Program of Translational Research in Acute Stroke Center at UCLA proposes an integrated research/training program to develop innovative therapies for acute ischemic and hemorrhagic stroke. Three research projects are proposed. Project 1, "The MR and Recanalization of Stroke Clots Using Embolectomy (MR RESCUE) Trial," will determine whether diffusion-perfusion MRI can identify patients who will benefit substantially from mechanical embolectomy with the Concentric Clot Retriever device for acute ischemic stroke up to 8 hrs from symptom onset. This study is a multicenter, randomized, controlled phase 2 trial of endovascular clot retrieval versus conventional medical care in 120 patients with large vessel, anterior circulation ischemic stroke 0-8 hrs from onset. Project 2, the "Hemorrhage Evacuation Employing MR-Guided Endoscopic Surgery (HEME-Surgery) Trial," is a phase 2, randomized, controlled, 60 patient trial of magnetic resonance guided endoscopic surgical evacuation vs. medical therapy within 24 h of acute intracerebral hemorrhage. This trial tests an innovative, minimally invasive surgical technique, applied early after onset, utilizing standard and novel clinical measures of outcome. In addition, studies interrogating the fundamental pathophysiology of brain injury in human ICH are proposed delineating differential

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gene expression, tissue morphometrics, and multimodal MR signatures in the perihematomal region. In Project 3, "Optimizing and Accelerating Prehospital Care of Acute Stroke," 3 inter-related studies will: prospectively validate a novel field measure of stroke severity, the Los Angeles Motor Scale (LAMS); improve dispatcher recognition of stroke by testing a new dispatcher-specific version of the Los Angeles Prehospital Stroke Screen (LAPSS-Dispatch); and demonstrate the feasibility, validity, and impact upon care of paramedic use of a novel, point of care test that assays 5 serum biomarkers to distinguish true stroke from nonstroke in the field. Five Cores will support the Projects: A) Patient Access, B) Blood / Tissue Specimen, C) Biostatistics / Data Management, D) Neuroimaging, E) Career Development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: UNRUPTURED INTRACRANIAL ANEURYSMS: NEUROLOGIC OUTCOME Principal Investigator & Institution: Torner, James C.; Professor and Head; Epidemiology; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2004; Project Start 15-MAR-2004; Project End 28-FEB-2008 Summary: (provided by applicant): Unruptured Intracranial Aneurysms (UIA) constitute a significant public health problem in the United States, which is growing in magnitude. The economic and social implications of optimizing clinical practice in this area are striking, given the considerable and escalating frequency with which UIAs are now detected in the population. The prevention of unnecessary death and disability related to UIA depends to a large degree upon a better understanding of the natural history of these lesions, as well as the short- and long-term benefits and risks associated with their repair. The current proposal represents a continuation of the prospective component of the International Study of Unruptured Intracranial Aneurysms (ISUIA). Its primary objectives center around defining the long-term risks of UIA rupture and other UIA natural history outcomes, risk factors associated with these natural history outcomes, long-term outcomes associated with endovascular and surgical repair of these lesions, and predictors of good and poor treatment outcomes. The first two phases of ISUIA have provided substantial and unique information regarding short-term prospective natural history and treatment outcomes, and have established that shortterm prospective natural history rupture rates are different than retrospective natural history rupture rates. The current proposal utilizes the large ISUIA cohort of patients established over the past ten years to provide vital long-term clinical information, which would otherwise be unobtainable. The current proposal involves the follow-up of living cases with UIA among the 4,060 cases in the prospective cohort, including 1,692 cases in the unoperated cohort and 2,368 cases in the cohort, which had UIA repair. The additional follow-up will allow the estimation of ten-year hemorrhage rates, and other outcome measures beyond the currently available five-year rates. It will also provide critical information on the long-term durability and effectiveness of endovascular and surgical treatment procedures, which are important in making clinical decisions regarding optimal management. Primary analyses will examine neurologic outcome, specifically fatal and non-fatal intracranial hemorrhagic strokes, secondary to aneurismal rupture and morbidity/mortality following UIA treatment. Secondary analyses will examine other aneurismal complications, such as ischemic stroke and death from all causes, including retreatment, durability of treatment, and functional endpoints, including Rankin, Barthel, and SF36 scores. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: UNRUPTURED INTRACRANIAL ANEURYSMS--NEUROLOGICAL OUTCOME Principal Investigator & Institution: Wiebers, David O.; Mayo Clinic Coll of Medicine, Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2002; Project Start 19-SEP-1991; Project End 31-AUG-2003 Summary: Unruptured intracranial aneurysms (UIA) constitute a significant public health problem in the United States (which is growing in magnitude). The prevention of hemorrhagic stroke in patients with UIA may be possible with a better understanding of the natural history of these lesions as well as the short and long-term benefits and risks associated with their repair. The current proposal represents a continuation of the first phase of the International Study of Unruptured Intracranial Aneurysms (ISUIA). Its primary objectives are to 1) define a critical aneurysm size above which there is a significant risk of future rupture among patients with UIA and no history of subarachnoid hemorrhage (SAH); 2) compare the risk of future rupture of UIA, disability, and death among patients with and without a history of prior SAH from a different source and to determine whether or not the risk of future rupture varies directly with aneurysmal size among patients with a history of prior SAH; and 3) define the surgical and endovascular morbidity and mortality involved with repair of UIA across a broad spectrum of populations, surgeons, and interventional neuroradiologists with special reference to the size and location of the aneurysm, history of SAH from another source, and other confounding variables such as age and associated medical conditions. The current proposal involves the prospective entry and follow-up of 2400 new cases with UIA (3500 total cases were entered in Phase I), and the continued followup of living cases with UIA entered to date at the 53 participating centers. The primary analysis will examine neurologic outcome, specifically, fatal and non-fatal intracranial hemorrhagic stroke secondary to aneurysmal rupture. Secondary analyses will examine other aneurysmal complications such as ischemic stroke and death from all causes. The prognostic significance of several independent clinical and radiological variables with respect to stroke due to aneurysmal rupture and mortality will also be analyzed using a Cox proportional hazards model. In addition, extensive planning has been undertaken to establish a molecular genetics component to this study to identify specific genetic defects predisposing the development and rupture of intracranial aneurysms. Funding for this component will be requested via a separate proposal submitted as a supplement to the current application. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, 3 4

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

With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.

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

Phenylpropanolamine and hemorrhagic stroke in women. by [No authors listed]; 2001 Mar 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=80844

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Tauroursodeoxycholic acid reduces apoptosis and protects against neurological injury after acute hemorrhagic stroke in rats. by Rodrigues CM, Sola S, Nan Z, Castro RE, Ribeiro PS, Low WC, Steer CJ.; 2003 May 13; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=156330

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

A quality-of-life instrument for young hemorrhagic stroke patients. Author(s): Hamedani AG, Wells CK, Brass LM, Kernan WN, Viscoli CM, Maraire JN, Awad IA, Horwitz RI. Source: Stroke; a Journal of Cerebral Circulation. 2001 March; 32(3): 687-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11239188

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After correcting for worse baseline characteristics, women treated with thrombolytic therapy for acute myocardial infarction have the same mortality and morbidity as men except for a higher incidence of hemorrhagic stroke. The Investigators of the International Tissue Plasminogen Activator/Streptokinase Mortality Study. Author(s): White HD, Barbash GI, Modan M, Simes J, Diaz R, Hampton JR, Heikkila J, Kristinsson A, Moulopoulos S, Paolasso EA, et al. Source: Circulation. 1993 November; 88(5 Pt 1): 2097-103. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8222103

6

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

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Age-related changes in risk factor effects on the incidence of thromboembolic and hemorrhagic stroke. Author(s): Abbott RD, Curb JD, Rodriguez BL, Masaki KH, Popper JS, Ross GW, Petrovitch H. Source: Journal of Clinical Epidemiology. 2003 May; 56(5): 479-86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12812823

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Alcohol and hemorrhagic stroke in Santiago, Chile. A case-control study. Author(s): Diaz V, Cumsille MA, Bevilacqua JA. Source: Neuroepidemiology. 2003 November-December; 22(6): 339-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14557684

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Alcohol and hemorrhagic stroke. The Honolulu Heart Program. Author(s): Donahue RP, Abbott RD, Reed DM, Yano K. Source: Jama : the Journal of the American Medical Association. 1986 May 2; 255(17): 2311-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3959320

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Alcohol drinking and risk of hemorrhagic stroke. Author(s): Klatsky AL, Armstrong MA, Friedman GD, Sidney S. Source: Neuroepidemiology. 2002 May-June; 21(3): 115-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12006774

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alpha(1)-antichymotrypsin polymorphism: a risk factor for hemorrhagic stroke in normotensive subjects. Author(s): Obach V, Revilla M, Vila N, Cervera A A, Chamorro A A. Source: Stroke; a Journal of Cerebral Circulation. 2001 November; 32(11): 2588-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11692021

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Ask the doctor. I am a 70-year-old man with high blood pressure that I control with medication, diet, and exercise. My mother, aunt, and maternal grandfather all died in their 50s after a single stroke. Is there an inherited tendency to hemorrhagic stroke? Are there any precautions I can take? Author(s): Lee TH. Source: Harvard Heart Letter : from Harvard Medical School. 2002 June; 12(10): 8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12079827

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Aspirin and hemorrhagic stroke. Author(s): Mayo NE, Levy AR, Goldberg MS. Source: Stroke; a Journal of Cerebral Circulation. 1991 September; 22(9): 1213-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1926268

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Aspirin and risk of hemorrhagic stroke. Author(s): Desbiens NA, Schmitt CM, Panda ML. Source: Jama : the Journal of the American Medical Association. 1999 August 25; 282(8): 732-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10463704

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Aspirin and risk of hemorrhagic stroke. Author(s): Tokuda Y, Kato J. Source: Jama : the Journal of the American Medical Association. 1999 August 25; 282(8): 732; Author Reply 732-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10463703

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Aspirin and risk of hemorrhagic stroke. Author(s): Colwell JA. Source: Jama : the Journal of the American Medical Association. 1999 August 25; 282(8): 731-2; Author Reply 732-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10463702

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Aspirin and risk of hemorrhagic stroke: a meta-analysis of randomized controlled trials. Author(s): He J, Whelton PK, Vu B, Klag MJ. Source: Jama : the Journal of the American Medical Association. 1998 December 9; 280(22): 1930-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9851479

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Aspirin and the risk of hemorrhagic stroke. Author(s): Rosenberg R. Source: The Journal of Family Practice. 1999 March; 48(3): 169-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10086752

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Asymptomatic pheochromocytoma. Diagnosis after hemorrhagic stroke in a middleaged patient. Author(s): Redman JC, Peloso OA, Milne RL, Kaminsky NI, Ellis SC, Wolfel DA, Martinez PU. Source: Postgraduate Medicine. 1983 April; 73(4): 279, 282-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6835878

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Body mass index and ischemic and hemorrhagic stroke: a prospective study in Korean men. Author(s): Song YM, Sung J, Davey Smith G, Ebrahim S. Source: Stroke; a Journal of Cerebral Circulation. 2004 April; 35(4): 831-6. Epub 2004 March 04. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15001798

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Circadian variability in hemorrhagic stroke. Author(s): Casetta I, Granieri E, Portaluppi F, Manfredini R. Source: Jama : the Journal of the American Medical Association. 2002 March 13; 287(10): 1266-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11886317

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Clinical diagnosis of ischemic versus hemorrhagic stroke: applicability of existing scores in the emergency situation and proposal of a new score. Author(s): Sturmer T, Schlindwein G, Kleiser B, Roempp A, Brenner H. Source: Neuroepidemiology. 2002 January-February; 21(1): 8-17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11744820

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Comparison of effect of glycoprotein IIb/IIIa inhibitors during percutaneous coronary interventions on risk of hemorrhagic stroke in patients >or=75 years of age versus those <75 years of age. Author(s): Iakovou I, Dangas G, Mehran R, Mintz GS, Lansky AJ, Aymong ED, Nikolsky E, Vagaonescu T, Glasser LA, Stone GW, Leon MB, Moses JW. Source: The American Journal of Cardiology. 2003 November 1; 92(9): 1083-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14583360

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Comparison of frequency of hemorrhagic stroke in patients <75 years versus > or =75 years of age among patients receiving glycoprotein IIb/IIIa inhibitors during percutaneous coronary interventions. Author(s): Iakovou I, Dangas G, Mintz GS, Mehran R, Lansky AJ, Aymong ED, Nikolsky E, Vagaonescu T, Glasser LA, Stone GW, Leon MB, Moses JW. Source: The American Journal of Cardiology. 2004 February 1; 93(3): 346-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14759388

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Complications of hemorrhagic stroke in children. Author(s): Humphreys RP. Source: Pediatric Neurosurgery. 1991-92; 17(3): 163-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1819332

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Computed tomography in the diagnosis of hemorrhagic stroke. Author(s): New PF. Source: Adv Neurol. 1977; 16: 145-68. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=868673

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CT and MRI in acute hemorrhagic stroke. Author(s): El-Koussy M, Guzman R, Bassetti C, Stepper F, Barth A, Lovblad KO, Schroth G. Source: Cerebrovascular Diseases (Basel, Switzerland). 2000 November-December; 10(6): 480-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11070382

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Delayed hemorrhagic stroke following accidental aluminium phosphide ingestion. Author(s): Dave HH, Dave TH, Rakholia VG, Kharod PN, Jaju HJ. Source: J Assoc Physicians India. 1994 January; 42(1): 78-9. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7836261

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Depressed platelet status in an elderly patient with hemorrhagic stroke after thrombolysis for acute myocardial infarction. Author(s): Cheung RT. Source: Stroke; a Journal of Cerebral Circulation. 1998 September; 29(9): 2002-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9731631

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Depressed platelet status in an elderly patient with hemorrhagic stroke after thrombolysis for acute myocardial infarction. GUSTO-III Investigators. Author(s): Serebruany VL, Gurbel PA, Shustov AR, Dalesandro MR, Gumbs CI, Grabletz LB, Bahr RD, Ohman EM, Topol EJ. Source: Stroke; a Journal of Cerebral Circulation. 1998 January; 29(1): 235-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9445356

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Differentiation between ischemic and hemorrhagic stroke by transcranial color-coded real-time sonography. Author(s): Becker G, Winkler J, Hofmann E, Bogdahn U. Source: Journal of Neuroimaging : Official Journal of the American Society of Neuroimaging. 1993 January; 3(1): 41-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10148076

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Endocarditis and hemorrhagic stroke caused by Cunninghamella bertholletiae infection after kidney transplantation. Author(s): Zhang R, Zhang JW, Szerlip HM. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 2002 October; 40(4): 842-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12324922

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Extent of pontine pyramidal tract Wallerian degeneration and outcome after supratentorial hemorrhagic stroke. Author(s): Fukui K, Iguchi I, Kito A, Watanabe Y, Sugita K. Source: Stroke; a Journal of Cerebral Circulation. 1994 June; 25(6): 1207-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8202981

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Functional outcome of ischemic and hemorrhagic stroke patients after inpatient rehabilitation: a matched comparison. Author(s): Paolucci S, Antonucci G, Grasso MG, Bragoni M, Coiro P, De Angelis D, Fusco FR, Morelli D, Venturiero V, Troisi E, Pratesi L. Source: Stroke; a Journal of Cerebral Circulation. 2003 December; 34(12): 2861-5. Epub 2003 November 13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14615613

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Hematology-neurology connection: Association between Factor XIII and hemorrhagic stroke in young women through genetic polymorphism. Author(s): Leclerc JR. Source: Stroke; a Journal of Cerebral Circulation. 2001 November; 32(11): 2586-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12619644

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Hematoma removal, heme, and heme oxygenase following hemorrhagic stroke. Author(s): Wagner KR, Dwyer BE. Source: Annals of the New York Academy of Sciences. 2004 March; 1012: 237-51. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15105270

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Hemorrhagic stroke as a complication of bacterial meningitis in adults: report of three cases and review. Author(s): Gironell A, Domingo P, Mancebo J, Coll P, Marti-Vilalta JL. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 1995 December; 21(6): 1488-91. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8749641

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Hemorrhagic stroke associated with the Iowa amyloid precursor protein mutation. Author(s): Greenberg SM, Shin Y, Grabowski TJ, Cooper GE, Rebeck GW, Iglesias S, Chapon F, Tournier-Lasserve E, Baron JC. Source: Neurology. 2003 March 25; 60(6): 1020-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12654973

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Hemorrhagic stroke due to cerebral vasculitis and the role of immunosuppressive therapy. Author(s): Cohen BA, Biller J. Source: Neurosurg Clin N Am. 1992 July; 3(3): 611-24. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1633484

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Hemorrhagic stroke in infancy, childhood, and adolescence. Author(s): Takeshita M, Kagawa M, Izawa M, Kitamura K. Source: Surgical Neurology. 1986 November; 26(5): 496-500. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3764653

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Hemorrhagic stroke: experience of an internal medicine department. Author(s): Vilas AP, Veiga MZ, Santos ME, Abecasis P. Source: Rev Port Cardiol. 2001 February; 20(2): 157-65. English, Portuguese. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11293874

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Hemorrhagic stroke: surgical treatment. Author(s): Graf CJ. Source: J Iowa Med Soc. 1969 July; 59(7): 575-85. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5791241

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Hyperhomocysteinemia as risk factor for ischemic and hemorrhagic stroke in newborn infants. Author(s): Hogeveen M, Blom HJ, Van Amerongen M, Boogmans B, Van Beynum IM, Van De Bor M. Source: The Journal of Pediatrics. 2002 September; 141(3): 429-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12219068

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I am undergoing treatment for hypertension and have been taking 200 mg of vitamin E daily for the past few years. I read that even lower doses might raise my risk of having a hemorrhagic stroke. Is this true? Author(s): Goldfinger SE. Source: Harvard Health Letter / from Harvard Medical School. 1999 January; 24(3): 3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10208116

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Improved functional outcome in patients with hemorrhagic stroke in putamen and thalamus compared with those with stroke restricted to the putamen or thalamus. Author(s): Miyai I, Suzuki T, Kang J, Volpe BT. Source: Stroke; a Journal of Cerebral Circulation. 2000 June; 31(6): 1365-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10835458

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Incidence of first-ever ischemic and hemorrhagic stroke in a well-defined community of southern Italy, 1993-1995. Author(s): Intiso D, Stampatore P, Zarrelli MM, Guerra GL, Arpaia G, Simone P, Tonali P, Beghi E. Source: European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies. 2003 September; 10(5): 559-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12940839

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Induction of mucosal tolerance to E-selectin targets immunomodulation to activating vessel segments and prevents ischemic and hemorrhagic stroke. Author(s): Takeda H, Spatz M, Ruetzler C, McCarron R, Becker K, Hallenbeck J. Source: Ernst Schering Res Found Workshop. 2004; (47): 117-32. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15032057

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Intensive care management of subarachnoid hemorrhage, ischemic stroke, and hemorrhagic stroke. Author(s): Martin NA, Saver J. Source: Clin Neurosurg. 1999; 45: 101-12. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10461507

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Intracranial aneurysm and hemorrhagic stroke in glucocorticoid-remediable aldosteronism. Author(s): Litchfield WR, Anderson BF, Weiss RJ, Lifton RP, Dluhy RG. Source: Hypertension. 1998 January; 31(1 Pt 2): 445-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9453343

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Is it clinically possible to distinguish nonhemorrhagic infarct from hemorrhagic stroke? Author(s): Besson G, Robert C, Hommel M, Perret J. Source: Stroke; a Journal of Cerebral Circulation. 1995 July; 26(7): 1205-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7604415

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Ischemic and hemorrhagic stroke in patients on oral anticoagulants after reconstruction for chronic lower limb ischemia. Author(s): Dawson I, van Bockel JH, Ferrari MD, van der Meer FJ, Brand R, Terpstra JL. Source: Stroke; a Journal of Cerebral Circulation. 1993 November; 24(11): 1655-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8236338

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Labetalol: response and safety in critically ill hemorrhagic stroke patients. Author(s): Patel RV, Kertland HR, Jahns BE, Zarowitz BJ, Mlynarek ME, Fagan SC. Source: The Annals of Pharmacotherapy. 1993 February; 27(2): 180-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8439694

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Leptin is a risk marker for first-ever hemorrhagic stroke in a population-based cohort. Author(s): Soderberg S, Ahren B, Stegmayr B, Johnson O, Wiklund PG, Weinehall L, Hallmans G, Olsson T. Source: Stroke; a Journal of Cerebral Circulation. 1999 February; 30(2): 328-37. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9933268

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Longitudinal changes of metabolites in frontal lobes after hemorrhagic stroke of basal ganglia: a proton magnetic resonance spectroscopy study. Author(s): Kobayashi M, Takayama H, Suga S, Mihara B. Source: Stroke; a Journal of Cerebral Circulation. 2001 October; 32(10): 2237-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11588307

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Low cholesterol in erythrocyte membranes and high lipoperoxides in erythrocytes are the potential risk factors for cerebral hemorrhagic stroke in human. Author(s): Chen HH, Zhou JF. Source: Biomed Environ Sci. 2001 September; 14(3): 189-98. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11723718

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Low serum cholesterol as a risk factor for hemorrhagic stroke in men: a communitybased mass screening in Okinawa, Japan. Author(s): Okumura K, Iseki K, Wakugami K, Kimura Y, Muratani H, Ikemiya Y, Fukiyama K. Source: Japanese Circulation Journal. 1999 January; 63(1): 53-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10084389

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Low total serum cholesterol and intracerebral hemorrhagic stroke: is the association confined to elderly men? The Kaiser Permanente Medical Care Program. Author(s): Iribarren C, Jacobs DR, Sadler M, Claxton AJ, Sidney S. Source: Stroke; a Journal of Cerebral Circulation. 1996 November; 27(11): 1993-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8898804

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Magnetic resonance imaging of cerebral hemorrhagic stroke. Author(s): Zaheer A, Ozsunar Y, Schaefer PW. Source: Topics in Magnetic Resonance Imaging : Tmri. 2000 October; 11(5): 288-99. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11142627

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Management of hemorrhagic stroke. Author(s): Tuhrim S. Source: Current Cardiology Reports. 2002 March; 4(2): 158-63. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11827640

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Medial pontine hemorrhagic stroke. Author(s): Ruhland JL, van Kan PL. Source: Physical Therapy. 2003 June; 83(6): 552-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12775201

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More on thrombolysis and hemorrhagic stroke. Author(s): Neuhaus KL. Source: Circulation. 1995 November 15; 92(10): 2794-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7586242

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Pentanucleotide TTTTA repeat polymorphism of apolipoprotein(a) gene and plasma lipoprotein(a) are associated with ischemic and hemorrhagic stroke in Chinese: a multicenter case-control study in China. Author(s): Sun L, Li Z, Zhang H, Ma A, Liao Y, Wang D, Zhao B, Zhu Z, Zhao J, Zhang Z, Wang W, Hui R. Source: Stroke; a Journal of Cerebral Circulation. 2003 July; 34(7): 1617-22. Epub 2003 June 05. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12791946

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Phenylpropanolamine and hemorrhagic stroke. Author(s): Ernst ME, Hartz A. Source: The New England Journal of Medicine. 2001 April 5; 344(14): 1094; Author Reply 1095. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11291667

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Phenylpropanolamine and hemorrhagic stroke. Author(s): Wolowich WR, Casavant MJ, Ekins BR. Source: The New England Journal of Medicine. 2001 April 5; 344(14): 1094-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11291666

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Phenylpropanolamine and the risk of hemorrhagic stroke. Author(s): Kernan WN, Viscoli CM, Brass LM, Broderick JP, Brott T, Feldmann E, Morgenstern LB, Wilterdink JL, Horwitz RI. Source: The New England Journal of Medicine. 2000 December 21; 343(25): 1826-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11117973

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Polymorphisms of coagulation factor XIII subunit A and risk of nonfatal hemorrhagic stroke in young white women. Author(s): Reiner AP, Schwartz SM, Frank MB, Longstreth WT Jr, Hindorff LA, Teramura G, Rosendaal FR, Gaur LK, Psaty BM, Siscovick DS. Source: Stroke; a Journal of Cerebral Circulation. 2001 November; 32(11): 2580-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11692020

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Prazosin-induced first-dose phenomenon possibly associated with hemorrhagic stroke: a report of three cases. Author(s): Lin MS, Hsieh WJ. Source: Drug Intell Clin Pharm. 1987 September; 21(9): 723-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3652934

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Precipitation of dysphagia due to achalasia cardia by hemorrhagic stroke. Author(s): Mukharia GK, Garg PK, Tandon RK. Source: The American Journal of Gastroenterology. 2002 June; 97(6): 1569-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12094894

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Prospective study on soluble thrombomodulin and von Willebrand factor and the risk of ischemic and hemorrhagic stroke. Author(s): Johansson L, Jansson JH, Boman K, Nilsson TK, Stegmayr B, Hallmans G. Source: Thrombosis and Haemostasis. 2002 February; 87(2): 211-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11858479

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Results in 95 hemorrhagic stroke patients included in CLASS, a controlled trial of clomethiazole versus placebo in acute stroke patients. Author(s): Wahlgren NG, Diez-Tejedor E, Teitelbaum J, Arboix A, Leys D, Ashwood T, Grossman E. Source: Stroke; a Journal of Cerebral Circulation. 2000 January; 31(1): 82-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10625720

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Risk factors for hemorrhagic stroke in Wonju, Korea. Author(s): Park JK, Kim HJ, Chang SJ, Koh SB, Koh SY. Source: Yonsei Medical Journal. 1998 June; 39(3): 229-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9664827

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Scoring systems for the differential diagnosis of ischemic and hemorrhagic stroke. Author(s): Weir CJ, Lees KR, Murray GD. Source: Stroke; a Journal of Cerebral Circulation. 1996 February; 27(2): 337-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8571434

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Serum cholesterol and hemorrhagic stroke in the Honolulu Heart Program. Author(s): Yano K, Reed DM, MacLean CJ. Source: Stroke; a Journal of Cerebral Circulation. 1989 November; 20(11): 1460-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2815179

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Smoking and risk of hemorrhagic stroke in women. Author(s): Kurth T, Kase CS, Berger K, Gaziano JM, Cook NR, Buring JE. Source: Stroke; a Journal of Cerebral Circulation. 2003 December; 34(12): 2792-5. Epub 2003 November 13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14615625

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Smoking and the risk of hemorrhagic stroke in men. Author(s): Kurth T, Kase CS, Berger K, Schaeffner ES, Buring JE, Gaziano JM. Source: Stroke; a Journal of Cerebral Circulation. 2003 May; 34(5): 1151-5. Epub 2003 March 27. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12663877

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Surgery on the carotid system in the treatment of hemorrhagic stroke. Author(s): Yasargil MG, Smith RD. Source: Adv Neurol. 1977; 16: 181-209. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=868675

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The Japanese experience in hemorrhagic stroke. Author(s): Omae T, Oita J, Ueda K. Source: Journal of Hypertension. Supplement : Official Journal of the International Society of Hypertension. 1994 December; 12(10): S19-23. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7769487

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The secular trend in the incidence of hemorrhagic stroke in the region of Osijek, Eastern Croatia in the period 1988-2000--a hospital based study. Author(s): Kadojic D, Barac B, Trkanjec Z, Kadojic M. Source: Coll Antropol. 2002 December; 26(2): 627-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12528292

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Transient elevation of serum bilirubin (a heme oxygenase-1 metabolite) level in hemorrhagic stroke: bilirubin is a marker of oxidant stress. Author(s): Dohi K, Mochizuki Y, Satoh K, Jimbo H, Hayashi M, Toyoda I, Ikeda Y, Abe T, Aruga T. Source: Acta Neurochir Suppl. 2003; 86: 247-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14753445

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Ultra high field MRI at 8 Tesla of subacute hemorrhagic stroke. Author(s): Novak V, Kangarlu A, Abduljalil A, Novak P, Slivka A, Chakeres D, Robitaille PM. Source: Journal of Computer Assisted Tomography. 2001 May-June; 25(3): 431-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11351195

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Underreporting of hemorrhagic stroke associated with phenylpropanolamine. Author(s): La Grenade L, Graham DJ, Nourjah P. Source: Jama : the Journal of the American Medical Association. 2001 December 26; 286(24): 3081. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11754672

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Unified Neurological Stroke Scale is valid in ischemic and hemorrhagic stroke. Author(s): Edwards DF, Chen YW, Diringer MN. Source: Stroke; a Journal of Cerebral Circulation. 1995 October; 26(10): 1852-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7570738

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Use of a heparinoid in patients with hemorrhagic stroke and thromboembolic disease. Author(s): Ten Cate H, Henny CP, Buller HR, Ten Cate JW, Magnani HN. Source: Annals of Neurology. 1984 March; 15(3): 268-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6721448

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CHAPTER 2. NUTRITION AND HEMORRHAGIC STROKE Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and hemorrhagic stroke.

Finding Nutrition Studies on Hemorrhagic Stroke The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements; National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: 301-435-2920, Fax: 301-480-1845, E-mail: [email protected]). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.7 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “hemorrhagic stroke” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

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

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

Cerebral vascular changes associated with hemorrhagic stroke in hypertension. Author(s): Department of Anaesthesia, McMaster University, Hamilton, Ont., Canada. Source: Smeda, J S Can-J-Physiol-Pharmacol. 1992 April; 70(4): 552-64 0008-4212

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Effect of poststroke captopril treatment on mortality associated with hemorrhagic stroke in stroke-prone rats. Author(s): Division of Basic Medical Sciences, Health Sciences Centre, Memorial University of Newfoundland, St. John's, Newfoundland, Canada. [email protected] Source: Smeda, J Vasdev, S King, S R J-Pharmacol-Exp-Ther. 1999 November; 291(2): 569-75 0022-3565

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Induction of mucosal tolerance to E-selectin prevents ischemic and hemorrhagic stroke in spontaneously hypertensive genetically stroke-prone rats. Author(s): Stroke Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Md 20892-4128, USA. Source: Takeda, H Spatz, M Ruetzler, C McCarron, R Becker, K Hallenbeck, J Stroke. 2002 September; 33(9): 2156-64 1524-4628

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Treatment of hemorrhagic stroke with arachidonic acid. Author(s): Institute of Brain Chemistry and Human Nutrition, University of North London, UK. Source: Golfetto, I Crawford Campo, R Nutr-Neurosci. 2001; 4(1): 75-9 1028-415X

Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •

healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

The following is a specific Web list relating to hemorrhagic stroke; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •

Vitamins Vitamin E Source: Prima Communications, Inc.www.personalhealthzone.com

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CHAPTER 3. ALTERNATIVE MEDICINE AND HEMORRHAGIC STROKE Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to hemorrhagic stroke. At the conclusion of this chapter, we will provide additional sources.

National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov/) has created a link to the National Library of Medicine’s databases to facilitate research for articles that specifically relate to hemorrhagic stroke and complementary medicine. To search the database, go to the following Web site: http://www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on PubMed.” Enter “hemorrhagic stroke” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of complementary and alternative medicine that are related to hemorrhagic stroke: •

Activity, participation, and quality of life 6 months poststroke. Author(s): Mayo NE, Wood-Dauphinee S, Cote R, Durcan L, Carlton J. Source: Archives of Physical Medicine and Rehabilitation. 2002 August; 83(8): 1035-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12161823

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Cerebral atheromatous embolism following carotid sinus pressure. Author(s): Beal MF, Park TS, Fisher CM. Source: Archives of Neurology. 1981 May; 38(5): 310-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7224920

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Circadian variation of blood pressure and the assessment of antihypertensive therapy. Author(s): White WB.

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Source: Blood Pressure Monitoring. 1999; 4 Suppl 1: S3-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10822410 •

Circadian variation of blood pressure: clinical relevance and implications for cardiovascular chronotherapeutics. Author(s): White WB. Source: Blood Pressure Monitoring. 1997 December; 2(1): 47-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10234091

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Clinical observation in 45 cases of hemorrhagic apoplexy of the acute stage treated by promoting blood circulation and removing blood stasis. Author(s): Sun G. Source: J Tradit Chin Med. 2003 June; 23(2): 96-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12875062

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Community-based prevention of stroke: nutritional improvement in Japan. Author(s): Yamori Y, Horie R. Source: Health Reports / Statistics Canada, Canadian Centre for Health Information = Rapports Sur La Sante / Statistique Canada, Centre Canadien D'information Sur La Sante. 1994; 6(1): 181-8. English, French. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7919079

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Consumption of fish and fish oils and decreased risk of stroke. Author(s): Skerrett PJ, Hennekens CH. Source: Preventive Cardiology. 2003 Winter; 6(1): 38-41. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12624561

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Delayed high dose contrast CT: identifying patients at risk of massive hemorrhagic infarction. Author(s): Hayman LA, Evans RA, Bastion FO, Hinck VC. Source: Ajr. American Journal of Roentgenology. 1981 June; 136(6): 1151-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6786028

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Diet and heart disease. The role of fat, alcohol, and antioxidants. Author(s): Gaziano JM, Manson JE. Source: Cardiology Clinics. 1996 February; 14(1): 69-83. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9072292

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Differences in stroke subtypes among natives and caucasians in Boston and Buenos Aires. Author(s): Saposnik G, Caplan LR, Gonzalez LA, Baird A, Dashe J, Luraschi A, Llinas R, Lepera S, Linfante I, Chaves C, Kanis K, Sica RE, Rey RC.

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Source: Stroke; a Journal of Cerebral Circulation. 2000 October; 31(10): 2385-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11022068 •

Effects of hemi-thalamic damage on K-complexes evoked by monaural stimuli during midafternoon sleep. Author(s): Weisz J, Soroker N, Oksenberg A, Myslobodsky MS. Source: Electroencephalography and Clinical Neurophysiology. 1995 February; 94(2): 148-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7532574

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Ethanol-induced contractions in cerebral arteries: role of tyrosine and mitogenactivated protein kinases. Author(s): Yang ZW, Wang J, Zheng T, Altura BT, Altura BM. Source: Stroke; a Journal of Cerebral Circulation. 2001 January; 32(1): 249-57. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11136944

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Fish consumption and risk of stroke in men. Author(s): He K, Rimm EB, Merchant A, Rosner BA, Stampfer MJ, Willett WC, Ascherio A. Source: Jama : the Journal of the American Medical Association. 2002 December 25; 288(24): 3130-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12495393

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Fish consumption and stroke: a community case-control study in Asturias, Spain. Author(s): Caicoya M. Source: Neuroepidemiology. 2002 May-June; 21(3): 107-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12006773

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Folate, vitamin B6, and B12 intakes in relation to risk of stroke among men. Author(s): He K, Merchant A, Rimm EB, Rosner BA, Stampfer MJ, Willett WC, Ascherio A. Source: Stroke; a Journal of Cerebral Circulation. 2004 January; 35(1): 169-74. Epub 2003 December 11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14671243

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Hemodynamic effects of 10% dextrose and of dextran 70 on hemorrhagic shock during exposure to hyperbaric air and hyperbaric hyperoxia. Author(s): Gross DR, Dodd KT, Welch DW, Fife WP. Source: Aviation, Space, and Environmental Medicine. 1984 December; 55(12): 1118-28. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6083773

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Hemodynamic effects of aortic occlusion during hemorrhagic shock and cardiac arrest.

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Author(s): Kralovich KA, Morris DC, Dereczyk BE, Simonetti V, Williams M, Rivers EP, Karmy-Jones R. Source: The Journal of Trauma. 1997 June; 42(6): 1023-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9210535 •

Hemodynamic studies of the effect of total alkaloids of datura in experimental hemorrhagic shock in dogs. Author(s): Zeng YM, Liu NH, Shen YT, Yang YF. Source: Resuscitation. 1982 June; 10(2): 129-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6294768

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Hemostatic variables in Japanese and Caucasian men. Plasma fibrinogen, factor VIIc, factor VIIIc, and von Willebrand factor and their relations to cardiovascular disease risk factors. Author(s): Iso H, Folsom AR, Wu KK, Finch A, Munger RG, Sato S, Shimamoto T, Terao A, Komachi Y. Source: American Journal of Epidemiology. 1989 November; 130(5): 925-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2510500

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IGF-I activity may be a key determinant of stroke risk--a cautionary lesson for vegans. Author(s): McCarty MF. Source: Medical Hypotheses. 2003 September; 61(3): 323-34. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12944100

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In vitro characterization of ephedrine-related stereoisomers at biogenic amine transporters and the receptorome reveals selective actions as norepinephrine transporter substrates. Author(s): Rothman RB, Vu N, Partilla JS, Roth BL, Hufeisen SJ, Compton-Toth BA, Birkes J, Young R, Glennon RA. Source: The Journal of Pharmacology and Experimental Therapeutics. 2003 October; 307(1): 138-45. Epub 2003 September 03. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12954796

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Intake of fish and omega-3 fatty acids and risk of stroke in women. Author(s): Iso H, Rexrode KM, Stampfer MJ, Manson JE, Colditz GA, Speizer FE, Hennekens CH, Willett WC. Source: Jama : the Journal of the American Medical Association. 2001 January 17; 285(3): 304-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11176840

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Ischemic stroke after using over the counter products containing ephedra. Author(s): Chen C, Biller J, Willing SJ, Lopez AM.

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Source: Journal of the Neurological Sciences. 2004 January 15; 217(1): 55-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14675610 •

Linoleic acid, other fatty acids, and the risk of stroke. Author(s): Iso H, Sato S, Umemura U, Kudo M, Koike K, Kitamura A, Imano H, Okamura T, Naito Y, Shimamoto T. Source: Stroke; a Journal of Cerebral Circulation. 2002 August; 33(8): 2086-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12154268

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Pharmacology of platelet activation-inhibitory drugs. Author(s): Rao GH, Rao AT. Source: Indian J Physiol Pharmacol. 1994 April; 38(2): 69-84. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8063366

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Pressor effect of electroacupuncture on hemorrhagic hypotension. Author(s): Syuu Y, Matsubara H, Hosogi S, Suga H. Source: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. 2003 December; 285(6): R1446-52. Epub 2003 July 31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12893654

•

The efficacy of combined physical and mental practice in the learning of a footsequence task after stroke: a case report. Author(s): Jackson PL, Doyon J, Richards CL, Malouin F. Source: Neurorehabilitation and Neural Repair. 2004 June; 18(2): 106-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15228806

•

Treatment of hemorrhagic stroke with arachidonic acid. Author(s): Golfetto I, Crawford, Campo R. Source: Nutritional Neuroscience. 2001; 4(1): 75-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11842878

•

Treatment of idiopathic thrombocytopenic purpura (ITP) in patients with refractoriness to or with contraindication for corticosteroids and/or splenectomy with immunosuppressive therapy and danazol. Author(s): Schiavotto C, Castaman G, Rodeghiero F. Source: Haematologica. 1993 November-December; 78(6 Suppl 2): 29-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8039755

•

Treatment of stroke with “five-center needling”: clinical observation of 78 cases. Author(s): Huang Y, Xia DB.

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Source: Di Yi June Yi Da Xue Xue Bao. 2002 July; 22(7): 657-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12376307 •

Use of Ephedra-containing products and risk for hemorrhagic stroke. Author(s): Karch SB. Source: Neurology. 2003 September 9; 61(5): 724-5; Author Reply 725. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12963785

•

Use of Ephedra-containing products and risk for hemorrhagic stroke. Author(s): Morgenstern LB, Viscoli CM, Kernan WN, Brass LM, Broderick JP, Feldmann E, Wilterdink JL, Brott T, Horwitz RI. Source: Neurology. 2003 January 14; 60(1): 132-5. Erratum In: Neurology. 2003 March 25; 60(6): 1055. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12525737

•

Vegan proteins may reduce risk of cancer, obesity, and cardiovascular disease by promoting increased glucagon activity. Author(s): McCarty MF. Source: Medical Hypotheses. 1999 December; 53(6): 459-85. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10687887

•

Vegetable oils high in phytosterols make erythrocytes less deformable and shorten the life span of stroke-prone spontaneously hypertensive rats. Author(s): Ratnayake WM, L'Abbe MR, Mueller R, Hayward S, Plouffe L, Hollywood R, Trick K. Source: The Journal of Nutrition. 2000 May; 130(5): 1166-78. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10801914

•

Vitamin E and beta carotene supplementation in high risk for stroke: a subgroup analysis of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Author(s): Leppala JM, Virtamo J, Fogelholm R, Albanes D, Taylor PR, Heinonen OP. Source: Archives of Neurology. 2000 October; 57(10): 1503-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11030804

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

Alternative Medicine Foundation, Inc.: http://www.herbmed.org/

•

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

•

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

Alternative Medicine 45

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

The following is a specific Web list relating to hemorrhagic stroke; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •

General Overview Atherosclerosis and Heart Disease Prevention Source: Prima Communications, Inc.www.personalhealthzone.com Cancer Prevention (Reducing the Risk) Source: Prima Communications, Inc.www.personalhealthzone.com Cataracts (prevention) Source: Prima Communications, Inc.www.personalhealthzone.com Obesity Source: Integrative Medicine Communications; www.drkoop.com Stroke Source: Healthnotes, Inc.; www.healthnotes.com Stroke Source: Integrative Medicine Communications; www.drkoop.com

•

Herbs and Supplements Phenylpropanolamine Source: Healthnotes, Inc.; www.healthnotes.com

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General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.

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CHAPTER 4. PATENTS ON HEMORRHAGIC STROKE Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.8 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “hemorrhagic stroke” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on hemorrhagic stroke, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Hemorrhagic Stroke By performing a patent search focusing on hemorrhagic stroke, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. 8Adapted

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

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

Substance abuse-induced hemorrhagic stoke in an animal model Inventor(s): Altura; Bella T. (Beechhurst, NY), Altura; Burton M. (Beechhurst, NY) Assignee(s): Research Foundation of the State University of New York (Albany, NY) Patent Number: 5,696,125 Date filed: February 24, 1995 Abstract: The present invention is an substance-induced-hemorrhagic stroke animal model. The substance-induced-hemorrhagic stroke animal model is useful in screening therapeutics for the prevention and/or treatment of stroke. The present invention also encompasses magnesium salt for the prevention and treatment of stroke. Excerpt(s): Despite its reputation as a beverage that can be used socially, acute "bingedrinking" of alcohol (e.g., more than 80 g ingested in <24 h) is associated with an evergrowing number of strokes and sudden death. This type of "binge-drinking" has been shown to result in intracerebral and subarachnoid hemorrhages as well as cerebral infarction (2, 3, 12, 17, 22-24). Onset of symptoms can occur within minutes to hours after this type of drinking. Particularly alarming are the increasing number of reports suggesting that even moderate alcohol elevates the risk of both intracerebral and subarachnoid hemorrhage (3,14). Although it is certain that alcohol "binge drinking" is a clear risk for stroke, it is by no means certain how these strokes are brought about (2, 3, 12, 14, 17, 22-24). Moreover, to our knowledge an animal model for alcohol-induced hemorrhagic stroke is not available. It has been reported that 10% of rats administered alcohol IP, in various doses (0.2-6.6 g/kg), developed hemorrhagic like strokes upon autopsy of the brain (6). Interestingly, this is about the incidence seen in the human experience (2, 3, 12, 14, 17, 22-24). Using direct in vivo microcirculatory studies on the rat brain, it has been shown previously that ethanol can induce concentration-dependent contractions of cerebral arterioles and venules followed by rupture of cerebral microvessels. The concentration range (10-500 mg/ml) used parallels that needed for its graded effects of euphoria, mental haziness, muscular incoordination, stupor, stroke, and coma in humans (5) Recent, preliminary in-situ observations on the rat brain indicate that perfusion of the cortical microcirculation with artificial cerebral spinal fluid containing reduced extracellular Mg.sup.3+ (›Mg.sup.2+ !) can result in spasms of arterioles and venules followed by rupture of venules and postcapillaries, leading to focal hemorrhages and brain edema (7). These results are, thus, very similar to that observed with administration of ethanol in normal, Mg.sup.2+ -sufficient brain preparations. Since it has long been known that chronic alcohol intake can deplete the human body of Mg (18), we hypothesized that alcohol-induced loss of ›Mg.sup.2+ !.sub.1 should precipitate cerebral vasospasm resulting in hypoxia, ischemia, and stroke in the brain, provided the dose of ethanol simulates the high doses in the human experience. In addition, Mg-pretreatment of such susceptible animals, which would yield ›Mg.sup.2+ !.sub.0 concentrations in the blood higher than normal, should protect against acute alcohol-induced stroke. The present invention is a stroke animal model. A method is provided that induces stroke in a mammal. In one aspect of the invention, the animal model is a model for substance abuse-induced hemorrhagic stroke. Web site: http://www.delphion.com/details?pn=US05696125__

Patents 49

Patent Applications on Hemorrhagic Stroke 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 hemorrhagic stroke: •

Microwave hemorrhagic stroke detector Inventor(s): Haddad, Waleed S.; (Dublin, CA), Trebes, James E.; (Livermore, CA) Correspondence: Lawrence Livermore; National Laboratory; 7000 East AVE., L.-703; Livermore; CA; 94550; US Patent Application Number: 20030018244 Date filed: September 23, 2002 Abstract: The microwave hemorrhagic stroke detector includes a low power pulsed microwave transmitter with a broad-band antenna for producing a directional beam of microwaves, an index of refraction matching cap placed over the patients head, and an array of broad-band microwave receivers with collection antennae. The system of microwave transmitter and receivers are scanned around, and can also be positioned up and down the axis of the patients head. The microwave hemorrhagic stroke detector is a completely non-invasive device designed to detect and localize blood pooling and clots or to measure blood flow within the head or body. The device is based on low power pulsed microwave technology combined with specialized antennas and tomographic methods. The system can be used for rapid, non-invasive detection of blood pooling such as occurs with hemorrhagic stoke in human or animal patients as well as for the detection of hemorrhage within a patient's body Excerpt(s): This is a continuation application of U.S. patent application Ser. No. 090/298,342, titled "Microwave Hemorrhagic Stroke Detector, filed Apr. 23, 1999, incorporated herein by reference. The present invention relates to the detection of the presence of blood pooling or blood flow within the body and within the head, and more specifically, it relates to the diagnosis of stroke. The are two forms of stroke: hemorrhagic and ischemic. Hemorrhagic stroke is caused by internal bleeding within the brain. Ischemic stroke is caused by blockage of a blood vessel that feeds the brain or a region of the brain. A stroke attack can occur suddenly and with little or no warning, and can result in severe physical impairment or death. Due to the rapid timescale for potentially severe or fatal damage to the brain these must be treated as rapidly as possible. Surgical intervention can be used to treat hemorrhagic stroke. An anti-clotting agent can be used to treat ischemic stroke. Unfortunately applying an anticlotting agent in the case of hemorrhagic stroke can cause fatal internal bleeding within the brain. At present, there is no non-invasive way to check patients for, and to differentiate between hemorrhagic and ischemic stroke other than computed tomography (CT) and magnetic resonance imaging (MRI). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

9

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

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Hemorrhagic Stroke

Keeping Current In order to stay informed about patents and patent applications dealing with hemorrhagic stroke, 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 “hemorrhagic stroke” (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 hemorrhagic stroke. You can also use this procedure to view pending patent applications concerning hemorrhagic stroke. 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 5. PERIODICALS AND NEWS ON HEMORRHAGIC STROKE Overview In this chapter, we suggest a number of news sources and present various periodicals that cover hemorrhagic stroke.

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

Smoking raises the risk of hemorrhagic stroke in men Source: Reuters Medical News Date: March 27, 2003

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•

Possible susceptibility markers for hemorrhagic stroke in young women identified Source: Reuters Industry Breifing Date: November 02, 2001

•

Low total cholesterol not a risk factor for hemorrhagic stroke in Korean men Source: Reuters Medical News Date: March 26, 2001

•

Seizures more common after hemorrhagic stroke than ischemic stroke Source: Reuters Medical News Date: November 22, 2000

•

Aspirin increases hemorrhagic stroke risk regardless of patient characteristics Source: Reuters Medical News Date: December 09, 1998 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 “hemorrhagic stroke” (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 “hemorrhagic stroke” (or synonyms). If you know the name of a company that is relevant to hemorrhagic stroke, you can go to any stock trading Web site (such as

Periodicals and News

53

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 “hemorrhagic stroke” (or synonyms).

Academic Periodicals covering Hemorrhagic Stroke Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to hemorrhagic stroke. In addition to these sources, you can search for articles covering hemorrhagic stroke 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 6. 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 hemorrhagic stroke. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a non-profit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI Advice for the Patient can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with hemorrhagic stroke. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.).

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The following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to hemorrhagic stroke: Laxatives •

Oral - U.S. Brands: Agoral; Alophen; Alphamul; Alramucil Orange; Alramucil Regular; Bisac-Evac; Black-Draught; Black-Draught Lax-Senna; Carter's Little Pills; Cholac; Citroma; Citrucel Orange Flavor; Citrucel Sugar-Free Orange Flavor; Colace; Constilac; Constulose; Correctol; Correctol Caplets; Correctol Herbal Tea; Correctol Stool Softener Soft Gels; D.O.S. Softgels; DC Softgels; Diocto; Diocto-C; Dioeze; Diosuccin; Docu-K Plus; DOK; DOK Softgels; Dr. Caldwell Senna Laxative; D-S-S; D-S-S plus; Dulcolax; Emulsoil; Enulose; Epsom salts; Equalactin; Evac-U-Gen; Ex-Lax; Ex-Lax Chocolate; FemiLax; Fiberall; Fibercon Caplets; Fiber-Lax; FiberNorm; Fleet Laxative; Fleet Mineral Oil; Fleet Phospho-Soda; Fleet Soflax Gelcaps; Fleet Soflax Overnight Gelcaps; Fletcher's Castoria; Genasoft Plus Softgels; Gentle Laxative; Haley's M-O; Herbal Laxative; Hydrocil Instant; Kondremul Plain; Konsyl; Konsyl Easy Mix; Konsyl-D; KonsylOrange; Konsyl-Orange Sugar Free; Laxinate 100; Liqui-Doss; Mag-Ox 400; Maltsupex; Metamucil; Metamucil Apple Crisp Fiber Wafers; Metamucil Cinnamon Spice Fiber Wafers; Metamucil Orange Flavor; Metamucil Smooth Sugar-Free, Citrus Flavor; Metamucil Smooth Sugar-Free, Orange Flavor; Metamucil Smooth Sugar-Free, Regular Flavor; Metamucil Smooth, Citrus Flavor; Metamucil Smooth, Orange Flavor; Metamucil Sugar-Free, Lemon-Lime Flavor; Metamucil Sugar-Free, Orange Flavor; MiraLax; Modane; Modane Bulk; Mylanta Natural Fiber Supplement; Mylanta Sugar Free Natural Fiber Supplement; Nature's Remedy; Neoloid; Perdiem; Perdiem Fiber; Peri-Colace; Peri-Dos Softgels; Phillips' Chewable; Phillips' Concentrated; Phillips' Milk of Magnesia; Phillips' Stool Softner Laxative Softgels; Prompt; Purge; Reguloid Natural; Reguloid Natural Sugar Free; Reguloid Orange; Reguloid Orange Sugar Free; Senexon; Senna-Gen; Senokot; Senokot Children's Syrup; Senokot-S; SenokotXTRA; Senolax; Serutan; Serutan Toasted Granules; Silace; Silace-C; Sulfolax; Surfak; Syllact; Veracolate; V-Lax; X-Prep Liquid http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202319.html

•

Rectal - U.S. Brands: Bisco-Lax; Ceo-Two; Dacodyl; Deficol; Dulcolax; Fleet Babylax; Fleet Bisacodyl; Fleet Enema; Fleet Enema for Children; Fleet Enema Mineral Oil; Fleet Glycerin Laxative; Fleet Laxative; Sani-Supp; Senokot; Theralax; Therevac Plus; Therevac-SB http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202320.html

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

Mosby’s Drug Consult Mosby’s Drug Consult database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing

Researching Medications

57

information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/. PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee. If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.

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APPENDICES

61

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 Institute10: •

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/

10

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

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Hemorrhagic Stroke

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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.11 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:12 •

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

11

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). 12 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 Gateway13 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.14 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “hemorrhagic stroke” (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 2140 7 887 6 29 3069

HSTAT15 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.16 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.17 Simply search by “hemorrhagic stroke” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

13

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

14

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). 15 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 16 17

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 Biologists18 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.19 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.20 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/.

18 Adapted 19

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. 20 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 hemorrhagic stroke can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internetbased 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 hemorrhagic stroke. 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 hemorrhagic stroke. 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 “hemorrhagic stroke”:

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African-American Health http://www.nlm.nih.gov/medlineplus/africanamericanhealth.html Circulatory Disorders http://www.nlm.nih.gov/medlineplus/circulatorydisorders.html Heart Diseases http://www.nlm.nih.gov/medlineplus/heartdiseases.html Stroke http://www.nlm.nih.gov/medlineplus/stroke.html Transient Ischemic Attack http://www.nlm.nih.gov/medlineplus/transientischemicattack.html You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The 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 hemorrhagic stroke. 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

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Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to hemorrhagic stroke. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with hemorrhagic stroke. 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 hemorrhagic stroke. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “hemorrhagic stroke” (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 “hemorrhagic stroke”. 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 “hemorrhagic stroke” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months.

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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 “hemorrhagic stroke” (or a synonym) into the search box, and click “Submit Query.”

71

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.21

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

21

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

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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)22: •

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/

22

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

Finding Medical Libraries

73

•

Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml

•

Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm

•

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

•

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

•

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

•

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

•

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

Finding Medical Libraries

75

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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•

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

•

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

•

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

•

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

77

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

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

•

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

•

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

•

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

•

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

•

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

•

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

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

Basic Guidelines for Hemorrhagic Stroke Hemorrhagic stroke Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000761.htm

•

Signs & Symptoms for Hemorrhagic Stroke Abnormal sensations Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003206.htm Agitated Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003212.htm Aphasia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003204.htm Breathing difficulties Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003075.htm

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Coma Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003202.htm Comatose Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003202.htm Consciousness changes Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003202.htm Contractures Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003185.htm Dizziness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003093.htm Edema Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003103.htm Eyelid drooping Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003035.htm Headache Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003024.htm High blood pressure Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003082.htm Incontinence Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003142.htm Lethargic 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 Loss of coordination Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003198.htm Loss of memory Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003257.htm Loss of movement Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003190.htm Loss of sensation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003206.htm Loss of vision Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003040.htm

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Muscle spasticity Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003193.htm Numbness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003206.htm Seizures Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003200.htm Sleepy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003208.htm Stuporous Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003202.htm Swallowing difficulties Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003115.htm Swelling Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003103.htm Tingling Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003206.htm Vertigo Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003093.htm Weakness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003174.htm •

Diagnostics and Tests for Hemorrhagic Stroke Bleeding time Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003656.htm CBC Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003642.htm CSF (cerebrospinal fluid) examination Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003625.htm CT Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003330.htm Head CT scan Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003786.htm Head MRI Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003791.htm Kidney function tests Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003435.htm

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Liver function tests Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003436.htm MRI Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003335.htm Orientation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003326.htm Partial thromboplastin time Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003653.htm Platelet count Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003647.htm PT Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003652.htm PTT Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003653.htm •

Surgery and Procedures for Hemorrhagic Stroke Gastrostomy tube Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002937.htm

•

Background Topics for Hemorrhagic Stroke 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 Embolism Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001124.htm Fractures Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000001.htm Hemorrhagic Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002373.htm Intravenous Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002383.htm Kidney function tests Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003435.htm Power of attorney Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001908.htm

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Safety Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001931.htm Stimuli Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002309.htm Unconscious Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000022.htm

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

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

•

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

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

•

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

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HEMORRHAGIC STROKE DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Ablation: The removal of an organ by surgery. [NIH] Acetylgalactosamine: The N-acetyl derivative of galactosamine. [NIH] Acetylglucosamine: The N-acetyl derivative of glucosamine. [NIH] Acoustic: Having to do with sound or hearing. [NIH] Adenylate Cyclase: An enzyme of the lyase class that catalyzes the formation of cyclic AMP and pyrophosphate from ATP. EC 4.6.1.1. [NIH] Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH] Adrenal Glands: Paired glands situated in the retroperitoneal tissues at the superior pole of each kidney. [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] Aeromedical: Pertaining to aviation medicine. [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] 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] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU]

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Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [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] 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] 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: Any organic compound containing an amino (-NH2 and a carboxyl (- COOH) group. The 20 a-amino acids listed in the accompanying table are the amino acids from which proteins are synthesized by formation of peptide bonds during ribosomal translation of messenger RNA; all except glycine, which is not optically active, have the L configuration. Other amino acids occurring in proteins, such as hydroxyproline in collagen, are formed by posttranslational enzymatic modification of amino acids residues in polypeptide chains. There are also several important amino acids, such as the neurotransmitter y-aminobutyric acid, that have no relation to proteins. Abbreviated AA. [EU] 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] Ampulla: A sac-like enlargement of a canal or duct. [NIH] Amygdala: Almond-shaped group of basal nuclei anterior to the inferior horn of the lateral ventricle of the brain, within the temporal lobe. The amygdala is part of the limbic system. [NIH]

Amyloid: A general term for a variety of different proteins that accumulate as extracellular fibrils of 7-10 nm and have common structural features, including a beta-pleated sheet conformation and the ability to bind such dyes as Congo red and thioflavine (Kandel, Schwartz, and Jessel, Principles of Neural Science, 3rd ed). [NIH] Amyloidosis: A group of diseases in which protein is deposited in specific organs (localized amyloidosis) or throughout the body (systemic amyloidosis). Amyloidosis may be either primary (with no known cause) or secondary (caused by another disease, including some types of cancer). Generally, primary amyloidosis affects the nerves, skin, tongue, joints, heart, and liver; secondary amyloidosis often affects the spleen, kidneys, liver, and adrenal glands. [NIH] Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Androgenic: Producing masculine characteristics. [EU]

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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] Aneurysm: A sac formed by the dilatation of the wall of an artery, a vein, or the heart. [NIH] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels from surrounding tissue to a solid tumor. This is caused by the release of chemicals by the tumor. [NIH] Angiopathy: Disease of the blood vessels (arteries, veins, and capillaries) that occurs when someone has diabetes for a long time. There are two types of angiopathy: macroangiopathy and microangiopathy. In macroangiopathy, fat and blood clots build up in the large blood vessels, stick to the vessel walls, and block the flow of blood. In microangiopathy, the walls of the smaller blood vessels become so thick and weak that they bleed, leak protein, and slow the flow of blood through the body. Then the cells, for example, the ones in the center of the eye, do not get enough blood and may be damaged. [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] 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]

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] Anticoagulants: Agents that prevent blood clotting. Naturally occurring agents in the blood are included only when they are used as drugs. [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] Antihypertensive: An agent that reduces high blood pressure. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Antioxidants: Naturally occurring or synthetic substances that inhibit or retard the oxidation of a substance to which it is added. They counteract the harmful and damaging effects of oxidation in animal tissues. [NIH] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Apolipoproteins: The protein components of lipoproteins which remain after the lipids to

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which the proteins are bound have been removed. They play an important role in lipid transport and metabolism. [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] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] 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] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Astigmatism: A condition in which the surface of the cornea is not spherical; causes a blurred image to be received at the retina. [NIH] Asymptomatic: Having no signs or symptoms of disease. [NIH] Atmospheric Pressure: The pressure at any point in an atmosphere due solely to the weight of the atmospheric gases above the point concerned. [NIH] 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] Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Autopsy: Postmortem examination of the body. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] 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] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around

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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] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Beta carotene: A vitamin A precursor. Beta carotene belongs to the family of fat-soluble vitamins called carotenoids. [NIH] Beta-pleated: Particular three-dimensional pattern of amyloidoses. [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] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological Transport: The movement of materials (including biochemical substances and drugs) across cell membranes and epithelial layers, usually by passive diffusion. [NIH] Biomarkers: Substances sometimes found in an increased amount in the blood, other body fluids, or tissues and that may suggest the presence of some types of cancer. Biomarkers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Bladder: The organ that stores urine. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blood 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]

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Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]

Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blotting and transferred to strips of nitrocellulose paper. The blots are then detected by radiolabeled antibody probes. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone scan: A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Brain Stem: The part of the brain that connects the cerebral hemispheres with the spinal cord. It consists of the mesencephalon, pons, and medulla oblongata. [NIH] Bypass: A surgical procedure in which the doctor creates a new pathway for the flow of body fluids. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Captopril: A potent and specific inhibitor of peptidyl-dipeptidase A. It blocks the conversion of angiotensin I to angiotensin II, a vasoconstrictor and important regulator of arterial blood pressure. Captopril acts to suppress the renin-angiotensin system and inhibits pressure responses to exogenous angiotensin. [NIH] Cardia: That part of the stomach surrounded by the esophagogastric junction, characterized by the lack of acid-forming cells. [NIH] Cardiac: Having to do with the heart. [NIH] Cardiac arrest: A sudden stop of heart function. [NIH] 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

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blood pressure). [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] Carotenoids: Substance found in yellow and orange fruits and vegetables and in dark green, leafy vegetables. May reduce the risk of developing cancer. [NIH] Carotid Sinus: The dilated portion of the common carotid artery at its bifurcation into external and internal carotids. It contains baroreceptors which, when stimulated, cause slowing of the heart, vasodilatation, and a fall in blood pressure. [NIH] Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes. [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] 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 Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Division: The fission of a cell. [NIH] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Centrifugation: A method of separating organelles or large molecules that relies upon differential sedimentation through a preformed density gradient under the influence of a gravitational field generated in a centrifuge. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Angiography: Radiography of the vascular system of the brain after injection of a contrast medium. [NIH] Cerebral Arteries: The arteries supplying the cerebral cortex. [NIH] Cerebral Cortex: The thin layer of gray matter on the surface of the cerebral hemisphere that develops from the telencephalon and folds into gyri. It reaches its highest development in man and is responsible for intellectual faculties and higher mental functions. [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 Hemorrhage: Bleeding into a cerebral hemisphere of the brain, including lobar, subcortical white matter, and basal ganglia hemorrhages. Commonly associated conditions include hypertension; intracranial arteriosclerosis; intracranial aneurysm; craniocerebral trauma; intracranial arteriovenous malformations; cerebral amyloid angiopathy; and cerebral infarction. [NIH] Cerebrospinal: Pertaining to the brain and spinal cord. [EU]

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Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] 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] Chest wall: The ribs and muscles, bones, and joints that make up the area of the body between the neck and the abdomen. [NIH] Chin: The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. [NIH] 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] Cholesterol Esters: Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a characteristic feature of atherosclerosis. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chylomicrons: A class of lipoproteins that carry dietary cholesterol and triglycerides from the small intestines to the tissues. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [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] Clot Retraction: Retraction of a clot resulting from contraction of platelet pseudopods attached to fibrin strands that is dependent on the contractile protein thrombosthenin. Used as a measure of platelet function. [NIH] Cluster Analysis: A set of statistical methods used to group variables or observations into strongly inter-related subgroups. In epidemiology, it may be used to analyze a closely grouped series of events or cases of disease or other health-related phenomenon with welldefined distribution patterns in relation to time or place or both. [NIH] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH]

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

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Compress: A plug used to occludate an orifice in the control of bleeding, or to mop up secretions; an absorbent pad. [NIH] Compulsions: In psychology, an irresistible urge, sometimes amounting to obsession to perform a particular act which usually is carried out against the performer's will or better judgment. [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] Confounding: Extraneous variables resulting in outcome effects that obscure or exaggerate the "true" effect of an intervention. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constriction: The act of constricting. [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] Contrast Media: Substances used in radiography that allow visualization of certain tissues. [NIH]

Convulsions: A general term referring to sudden and often violent motor activity of cerebral or brainstem origin. Convulsions may also occur in the absence of an electrical cerebral discharge (e.g., in response to hypotension). [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH]

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Corpuscle: A small mass or body; a sensory nerve end bulb; a cell, especially that of the blood or the lymph. [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] Criterion: A standard by which something may be judged. [EU] Critical Care: Health care provided to a critically ill patient during a medical emergency or crisis. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] 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] Danazol: A synthetic steroid with antigonadotropic and anti-estrogenic activities that acts as an anterior pituitary suppressant by inhibiting the pituitary output of gonadotropins. It possesses some androgenic properties. Danazol has been used in the treatment of endometriosis and some benign breast disorders. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] 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] Diagnostic procedure: A method used to identify a disease. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Diencephalon: The paired caudal parts of the prosencephalon from which the thalamus, hypothalamus, epithalamus, and subthalamus are derived. [NIH] Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Disparity: Failure of the two retinal images of an object to fall on corresponding retinal

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points. [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] Double-blind: Pertaining to a clinical trial or other experiment in which neither the subject nor the person administering treatment knows which treatment any particular subject is receiving. [EU] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Duodenum: The first part of the small intestine. [NIH] 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] Dysphagia: Difficulty in swallowing. [EU] Echo-Planar Imaging: A type of magnetic resonance imaging that uses only one nuclear spin excitation per image and therefore can obtain images in a fraction of a second rather than the minutes required in traditional MRI techniques. It is used in a variety of medical and scientific applications. [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] 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] Electroacupuncture: A form of acupuncture using low frequency electrically stimulated needles to produce analgesia and anesthesia and to treat disease. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Elementary Particles: Individual components of atoms, usually subatomic; subnuclear

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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] Embolectomy: Surgical removal of an obstructing clot or foreign material which has been transported from a distant vessel by the bloodstream. Removal of a clot at its original site is called thrombectomy. [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] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endorphins: One of the three major groups of endogenous opioid peptides. They are large peptides derived from the pro-opiomelanocortin precursor. The known members of this group are alpha-, beta-, and gamma-endorphin. The term endorphin is also sometimes used to refer to all opioid peptides, but the narrower sense is used here; opioid peptides is used for the broader group. [NIH] Endoscope: A thin, lighted tube used to look at tissues inside the body. [NIH] Endoscopic: A technique where a lateral-view endoscope is passed orally to the duodenum for visualization of the ampulla of Vater. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxins: Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells. [NIH] Enkephalins: One of the three major families of endogenous opioid peptides. The enkephalins are pentapeptides that are widespread in the central and peripheral nervous systems and in the adrenal medulla. [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] Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. [NIH] Ephedrine: An alpha- and beta-adrenergic agonist that may also enhance release of norepinephrine. It has been used in the treatment of several disorders including asthma, heart failure, rhinitis, and urinary incontinence, and for its central nervous system stimulatory effects in the treatment of narcolepsy and depression. It has become less

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extensively used with the advent of more selective agonists. [NIH] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Erythrocyte Membrane: The semipermeable outer portion of the red corpuscle. It is known as a 'ghost' after hemolysis. [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] Essential Tremor: A rhythmic, involuntary, purposeless, oscillating movement resulting from the alternate contraction and relaxation of opposing groups of muscles. [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] Euphoria: An exaggerated feeling of physical and emotional well-being not consonant with apparent stimuli or events; usually of psychologic origin, but also seen in organic brain disease and toxic states. [NIH] Evacuation: An emptying, as of the bowels. [EU] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] 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 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] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] 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 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

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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] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fibril: Most bacterial viruses have a hollow tail with specialized fibrils at its tip. The tail fibers attach to the cell wall of the host. [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] Filler: An inactive substance used to make a product bigger or easier to handle. For example, fillers are often used to make pills or capsules because the amount of active drug is too small to be handled conveniently. [NIH] Fish Oils: Oils high in unsaturated fats extracted from the bodies of fish or fish parts, especially the livers. Those from the liver are usually high in vitamin A. The oils are used as dietary supplements, in soaps and detergents, as protective coatings, and as a base for other food products such as vegetable shortenings. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Fractionation: Dividing the total dose of radiation therapy into several smaller, equal doses delivered over a period of several days. [NIH] Frontal Lobe: The anterior part of the cerebral hemisphere. [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] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Therapy: The introduction of new genes into cells for the purpose of treating disease by restoring or adding gene expression. Techniques include insertion of retroviral vectors, transfection, homologous recombination, and injection of new genes into the nuclei of single cell embryos. The entire gene therapy process may consist of multiple steps. The new genes may be introduced into proliferating cells in vivo (e.g., bone marrow) or in vitro (e.g.,

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fibroblast cultures) and the modified cells transferred to the site where the gene expression is required. Gene therapy may be particularly useful for treating enzyme deficiency diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug sensitivity, particularly for leukemia. [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genomics: The systematic study of the complete DNA sequences (genome) of organisms. [NIH]

Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] 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] Globus Pallidus: The representation of the phylogenetically oldest part of the corpus striatum called the paleostriatum. It forms the smaller, more medial part of the lentiform nucleus. [NIH] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] 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] 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] 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] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [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] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH]

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Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Heartbeat: One complete contraction of the heart. [NIH] 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 prosthetic group in many hemeproteins. [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] Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. [NIH] Hemolysis: The destruction of erythrocytes by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]

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] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hydration: Combining with water. [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] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU]

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Hyperbaric: Characterized by greater than normal pressure or weight; applied to gases under greater than atmospheric pressure, as hyperbaric oxygen, or to a solution of greater specific gravity than another taken as a standard of reference. [EU] Hyperbaric oxygen: Oxygen that is at an atmospheric pressure higher than the pressure at sea level. Breathing hyperbaric oxygen to enhance the effectiveness of radiation therapy is being studied. [NIH] Hyperopia: Farsightedness; ability to see distant objects more clearly than close objects; may be corrected with glasses or contact lenses. [NIH] Hyperoxia: An abnormal increase in the amount of oxygen in the tissues and organs. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hypotension: Abnormally low blood pressure. [NIH] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Idiopathic: Describes a disease of unknown cause. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunoblotting: Immunologic methods for isolating and quantitatively measuring immunoreactive substances. When used with immune reagents such as monoclonal antibodies, the process is known generically as western blot analysis (blotting, western). [NIH]

Immunoglobulins: Glycoproteins present in the blood (antibodies) and in other tissue. They are classified by structure and activity into five classes (IgA, IgD, IgE, IgG, IgM). [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive therapy: Therapy used to decrease the body's immune response, such as drugs given to prevent transplant rejection. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] 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] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic

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clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Ingestion: Taking into the body by mouth [NIH] 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] 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] Intracellular: Inside a cell. [NIH] Intracranial Aneurysm: A saclike dilatation of the walls of a blood vessel, usually an artery. [NIH]

Intracranial Arteriosclerosis: Vascular diseases characterized by thickening, hardening, and remodeling of the walls of intracranial arteries. There are three subtypes: (1) atherosclerosis, marked by fatty depositions in the innermost layer of the arterial walls, (2) Monckeberg's sclerosis, which features calcium deposition in the media and (3) arteriolosclerosis, which refers to sclerosis of small caliber arteries. Clinically, this process may be associated with transient ischemic attack, brain infarction, intracranial embolism and thrombosis, or intracranial aneurysm. [NIH] Intravascular: Within a vessel or vessels. [EU] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

Involuntary: Reaction occurring without intention or volition. [NIH] 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] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Ischemic stroke: A condition in which the blood supply to part of the brain is cut off. Also called "plug-type" strokes. Blocked arteries starve areas of the brain controlling sight, speech, sensation, and movement so that these functions are partially or completely lost. Ischemic stroke is the most common type of stroke, accounting for 80 percent of all strokes. Most ischemic strokes are caused by a blood clot called a thrombus, which blocks blood flow in the arteries feeding the brain, usually the carotid artery in the neck, the major vessel bringing blood to the brain. When it becomes blocked, the risk of stroke is very high. [NIH] 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]

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Kidney Transplantation: The transference of a kidney from one human or animal to another. [NIH] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Least-Squares Analysis: A principle of estimation in which the estimates of a set of parameters in a statistical model are those quantities minimizing the sum of squared differences between the observed values of a dependent variable and the values predicted by the model. [NIH] Lenses: Pieces of glass or other transparent materials used for magnification or increased visual acuity. [NIH] Lesion: An area of abnormal tissue change. [NIH] Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Likelihood Functions: Functions constructed from a statistical model and a set of observed data which give the probability of that data for various values of the unknown model parameters. Those parameter values that maximize the probability are the maximum likelihood estimates of the parameters. [NIH] Linear Models: Statistical models in which the value of a parameter for a given value of a factor is assumed to be equal to a + bx, where a and b are constants. The models predict a linear regression. [NIH] 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] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Lipoprotein(a): A family of lipoprotein particles varying in density and size depending on the protein-lipid ratio and the protein composition. These particles consist of apolipoprotein B-100 covalently linked to apolipoprotein-a by one or two disulfide bonds. There is a correlation between high plasma levels of this lipoprotein and increased risk for atherosclerotic cardiovascular disease. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver scan: An image of the liver created on a computer screen or on film. A radioactive substance is injected into a blood vessel and travels through the bloodstream. It collects in the liver, especially in abnormal areas, and can be detected by the scanner. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH]

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Logistic Models: Statistical models which describe the relationship between a qualitative dependent variable (that is, one which can take only certain discrete values, such as the presence or absence of a disease) and an independent variable. A common application is in epidemiology for estimating an individual's risk (probability of a disease) as a function of a given risk factor. [NIH] Low-density lipoprotein: Lipoprotein that contains most of the cholesterol in the blood. LDL carries cholesterol to the tissues of the body, including the arteries. A high level of LDL increases the risk of heart disease. LDL typically contains 60 to 70 percent of the total serum cholesterol and both are directly correlated with CHD risk. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [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] Magnetic Resonance Angiography: Non-invasive method of vascular imaging and determination of internal anatomy without injection of contrast media or radiation exposure. The technique is used especially in cerebral angiography as well as for studies of other vascular structures. [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] Malformation: A morphologic developmental process. [EU]

defect

resulting

from

an

intrinsically

abnormal

Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]

Mass Screening: Organized periodic procedures performed on large groups of people for the purpose of detecting disease. [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] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Medullary: Pertaining to the marrow or to any medulla; resembling marrow. [EU] Melanin: The substance that gives the skin its color. [NIH]

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Membrane: A very thin layer of tissue that covers a surface. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] 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] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Health: The state wherein the person is well adjusted. [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] Meta-Analysis: A quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with application chiefly in the areas of research and medicine. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] 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] 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] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Middle Cerebral Artery: The largest and most complex of the cerebral arteries. Branches of the middle cerebral artery supply the insular region, motor and premotor areas, and large regions of the association cortex. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [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] Mitogen-Activated Protein Kinase Kinases: A serine-threonine protein kinase family whose members are components in protein kinase cascades activated by diverse stimuli. These MAPK kinases phosphorylate mitogen-activated protein kinases and are themselves phosphorylated by MAP kinase kinase kinases. JNK kinases (also known as SAPK kinases) are a subfamily. EC 2.7.10.- [NIH] Mitogen-Activated Protein Kinases: A superfamily of protein-serine-threonine kinases that

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are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by mitogen-activated protein kinase kinases which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP kinase kinase kinases). Families of these mitogen-activated protein kinases (MAPKs) include extracellular signal-regulated kinases (ERKs), stress-activated protein kinases (SAPKs) (also known as c-jun terminal kinases (JNKs)), and p38-mitogen-activated protein kinases. EC 2,7,1.- [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] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monoclonal antibodies: Laboratory-produced substances that can locate and bind to cancer cells wherever they are in the body. Many monoclonal antibodies are used in cancer detection or therapy; each one recognizes a different protein on certain cancer cells. Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to a tumor. [NIH] Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. [NIH] Mononuclear: A cell with one nucleus. [NIH] 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] Myelin: The fatty substance that covers and protects nerves. [NIH] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myopia: That error of refraction in which rays of light entering the eye parallel to the optic axis are brought to a focus in front of the retina, as a result of the eyeball being too long from front to back (axial m.) or of an increased strength in refractive power of the media of the eye (index m.). Called also nearsightedness, because the near point is less distant than it is in emmetropia with an equal amplitude of accommodation. [EU] Narcolepsy: A condition of unknown cause characterized by a periodic uncontrollable tendency to fall asleep. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes

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that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Neostriatum: The phylogenetically newer part of the corpus striatum consisting of the caudate nucleus and putamen. It is often called simply the striatum. [NIH] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nerve Endings: Specialized terminations of peripheral neurons. Nerve endings include neuroeffector junction(s) by which neurons activate target organs and sensory receptors which transduce information from the various sensory modalities and send it centrally in the nervous system. Presynaptic nerve endings are presynaptic terminals. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] 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] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] 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] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]

Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a

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widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Normotensive: 1. Characterized by normal tone, tension, or pressure, as by normal blood pressure. 2. A person with normal blood pressure. [EU] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Obsessive-Compulsive Disorder: An anxiety disorder characterized by recurrent, persistent obsessions or compulsions. Obsessions are the intrusive ideas, thoughts, or images that are experienced as senseless or repugnant. Compulsions are repetitive and seemingly purposeful behavior which the individual generally recognizes as senseless and from which the individual does not derive pleasure although it may provide a release from tension. [NIH] Omega-3 fatty acid: A type of fat obtained in the diet and involved in immunity. [NIH] Opacity: Degree of density (area most dense taken for reading). [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] 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]

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] Pachymeningitis: Inflammation of the dura mater of the brain, the spinal cord or the optic nerve. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Paralysis: Loss of ability to move all or part of the body. [NIH] Paramedic: An emergency medical technician (EMT) who received further training for the delivery of some aspects of advanced life support (ALS) care. [NIH] Particle: A tiny mass of material. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

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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] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Pelvic: Pertaining to the pelvis. [EU] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Percutaneous: Performed through the skin, as injection of radiopacque material in radiological examination, or the removal of tissue for biopsy accomplished by a needle. [EU] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Perfusion magnetic resonance imaging: A type of magnetic resonance imaging (MRI) used to check the flow of blood to normal tissue and diseased tissue. [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] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] 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] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phenylpropanolamine: A sympathomimetic that acts mainly by causing release of norepinephrine but also has direct agonist activity at some adrenergic receptors. It is most commonly used as a nasal vasoconstrictor and an appetite depressant. [NIH] 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] 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] 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

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skin, eyes, and hair. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU] 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] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]

Pneumonia: Inflammation of the lungs. [NIH] Pneumothorax: Accumulation of air or gas in the space between the lung and chest wall, resulting in partial or complete collapse of the lung. [NIH] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called

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tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Pons: The part of the central nervous system lying between the medulla oblongata and the mesencephalon, ventral to the cerebellum, and consisting of a pars dorsalis and a pars ventralis. [NIH] Postoperative: After surgery. [NIH] Post-synaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potassium Channels: Cell membrane glycoproteins selective for potassium ions. [NIH] Practicability: A non-standard characteristic of an analytical procedure. It is dependent on the scope of the method and is determined by requirements such as sample throughout and costs. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] 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] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] 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] 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] Prone: Having the front portion of the body downwards. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostaglandins: A group of compounds derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway. They are extremely potent mediators of a diverse group of physiological processes. [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] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a

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protein). [EU] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Kinase C: An enzyme that phosphorylates proteins on serine or threonine residues in the presence of physiological concentrations of calcium and membrane phospholipids. The additional presence of diacylglycerols markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by phorbol esters and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters. EC 2.7.1.-. [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] Protein-Serine-Threonine Kinases: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors. EC 2.7.10. [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] 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] 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] Purpura: Purplish or brownish red discoloration, easily visible through the epidermis, caused by hemorrhage into the tissues. [NIH] Putamen: The largest and most lateral of the basal ganglia lying between the lateral

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medullary lamina of the globus pallidus and the external capsule. It is part of the neostriatum and forms part of the lentiform nucleus along with the globus pallidus. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radar: A system using beamed and reflected radio signals to and from an object in such a way that range, bearing, and other characteristics of the object may be determined. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radioactive: Giving off radiation. [NIH] 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] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Randomized Controlled Trials: Clinical trials that involve at least one test treatment and one control treatment, concurrent enrollment and follow-up of the test- and control-treated groups, and in which the treatments to be administered are selected by a random process, such as the use of a random-numbers table. Treatment allocations using coin flips, odd-even numbers, patient social security numbers, days of the week, medical record numbers, or other such pseudo- or quasi-random processes, are not truly randomized and trials employing any of these techniques for patient assignment are designated simply controlled clinical trials. [NIH] 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] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] 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] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH]

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Regression Analysis: Procedures for finding the mathematical function which best describes the relationship between a dependent variable and one or more independent variables. In linear regression (see linear models) the relationship is constrained to be a straight line and least-squares analysis is used to determine the best fit. In logistic regression (see logistic models) the dependent variable is qualitative rather than continuously variable and likelihood functions are used to find the best relationship. In multiple regression the dependent variable is considered to depend on more than a single independent variable. [NIH]

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] Renin: An enzyme which is secreted by the kidney and is formed from prorenin in plasma and kidney. The enzyme cleaves the Leu-Leu bond in angiotensinogen to generate angiotensin I. EC 3.4.23.15. (Formerly EC 3.4.99.19). [NIH] Renin-Angiotensin System: A system consisting of renin, angiotensin-converting enzyme, and angiotensin II. Renin, an enzyme produced in the kidney, acts on angiotensinogen, an alpha-2 globulin produced by the liver, forming angiotensin I. The converting enzyme contained in the lung acts on angiotensin I in the plasma converting it to angiotensin II, the most powerful directly pressor substance known. It causes contraction of the arteriolar smooth muscle and has other indirect actions mediated through the adrenal cortex. [NIH] Reperfusion: Restoration of blood supply to tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. It is primarily a procedure for treating infarction or other ischemia, by enabling viable ischemic tissue to recover, thus limiting further necrosis. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing reperfusion injury. [NIH] Reperfusion Injury: Functional, metabolic, or structural changes, including necrosis, in ischemic tissues thought to result from reperfusion to ischemic areas of the tissue. The most common instance is myocardial reperfusion injury. [NIH] 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] Retreatment: The therapy of the same disease in a patient, with the same agent or procedure repeated after initial treatment, or with an additional or alternate measure or follow-up. It does not include therapy which requires more than one administration of a therapeutic agent or regimen. Retreatment is often used with reference to a different modality when the original one was inadequate, harmful, or unsuccessful. [NIH] Retrospective: Looking back at events that have already taken place. [NIH] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [NIH] Rhinitis: Inflammation of the mucous membrane of the nose. [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

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attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] 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] Screening: Checking for disease when there are no symptoms. [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] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Sensor: A device designed to respond to physical stimuli such as temperature, light, magnetism or movement and transmit resulting impulses for interpretation, recording, movement, or operating control. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] 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] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]

Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH]

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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 Security: Government sponsored social insurance programs. [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] 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] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] 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] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Splenectomy: An operation to remove the spleen. [NIH] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH]

Stasis: A word termination indicating the maintenance of (or maintaining) a constant level; preventing increase or multiplication. [EU]

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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] Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] 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] 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]

Sudden death: Cardiac arrest caused by an irregular heartbeat. The term "death" is somewhat misleading, because some patients survive. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Supratentorial: Located in the upper part of the brain. [NIH] Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Synapse: The region where the processes of two neurons come into close contiguity, and the nervous impulse passes from one to the other; the fibers of the two are intermeshed, but, according to the general view, there is no direct contiguity. [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]

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Synaptosomes: Pinched-off nerve endings and their contents of vesicles and cytoplasm together with the attached subsynaptic area of the membrane of the post-synaptic cell. They are largely artificial structures produced by fractionation after selective centrifugation of nervous tissue homogenates. [NIH] Systemic: Affecting the entire body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Telencephalon: Paired anteriolateral evaginations of the prosencephalon plus the lamina terminalis. The cerebral hemispheres are derived from it. Many authors consider cerebrum a synonymous term to telencephalon, though a minority include diencephalon as part of the cerebrum (Anthoney, 1994). [NIH] 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] Thalamic: Cell that reaches the lateral nucleus of amygdala. [NIH] Thalamus: Paired bodies containing mostly gray substance and forming part of the lateral wall of the third ventricle of the brain. The thalamus represents the major portion of the diencephalon and is commonly divided into cellular aggregates known as nuclear groups. [NIH]

Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] 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] Thrombectomy: Surgical removal of an obstructing clot or foreign material from a blood vessel at the point of its formation. Removal of a clot arising from a distant site is called embolectomy. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [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] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]

Thromboplastin: Constituent composed of protein and phospholipid that is widely distributed in many tissues. It serves as a cofactor with factor VIIa to activate factor X in the extrinsic pathway of blood coagulation. [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]

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Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Plasminogen Activator: A proteolytic enzyme in the serine protease family found in many tissues which converts plasminogen to plasmin. It has fibrin-binding activity and is immunologically different from urinary plasminogen activator. The primary sequence, composed of 527 amino acids, is identical in both the naturally occurring and synthetic proteases. EC 3.4.21.68. [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] Tone: 1. The normal degree of vigour and tension; in muscle, the resistance to passive elongation or stretch; tonus. 2. A particular quality of sound or of voice. 3. To make permanent, or to change, the colour of silver stain by chemical treatment, usually with a heavy metal. [EU] 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] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] 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] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy,

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effectiveness, safety, practicability, etc., of these interventions in individual cases or series. [NIH]

Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] 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] Unsaturated Fats: A type of fat. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary Plasminogen Activator: A proteolytic enzyme that converts plasminogen to plasmin where the preferential cleavage is between arginine and valine. It was isolated originally from human urine, but is found in most tissues of most vertebrates. EC 3.4.21.73. [NIH]

Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasculitis: Inflammation of a blood vessel. [NIH] Vasodilatation: A state of increased calibre of the blood vessels. [EU] Vasodilator: An agent that widens blood vessels. [NIH] VE: The total volume of gas either inspired or expired in one minute. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [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] 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]

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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] 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]

Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH]

121

INDEX A Ablation, 15, 83 Acetylgalactosamine, 83, 98 Acetylglucosamine, 83, 98 Acoustic, 16, 83 Adenylate Cyclase, 7, 83 Adolescence, 28, 83 Adrenal Glands, 83, 84 Adrenal Medulla, 83, 95, 96, 106 Adrenergic, 12, 83, 94, 95, 96, 108, 116 Adverse Effect, 14, 83, 114 Aeromedical, 11, 83 Affinity, 83, 115 Agonist, 83, 94, 95, 108 Albumin, 83, 109 Algorithms, 15, 84, 87 Allylamine, 84 Alternative medicine, 52, 84 Amine, 42, 84 Amino acid, 84, 86, 96, 98, 108, 109, 111, 114, 116, 118, 119 Ammonia, 84 Ampulla, 84, 95 Amygdala, 84, 117 Amyloid, 5, 6, 13, 17, 18, 27, 84, 89 Amyloidosis, 5, 6, 18, 84 Anaphylatoxins, 84, 91 Anatomical, 84, 90, 100 Androgenic, 84, 93 Anesthesia, 85, 94 Aneurysm, 14, 21, 29, 85 Angiogenesis, 85, 103 Angiopathy, 6, 13, 17, 18, 85, 89 Animal model, 5, 6, 17, 18, 48, 85 Antibacterial, 85, 115 Antibiotic, 85, 115 Antibody, 83, 85, 88, 91, 99, 100, 103, 105, 115 Anticoagulants, 29, 85 Antigen, 83, 85, 91, 99, 100, 103 Antigen-Antibody Complex, 85, 91 Antihypertensive, 39, 85 Anti-inflammatory, 85, 98 Antioxidants, 10, 40, 85 Anus, 85, 91 Anxiety, 85, 107 Apolipoproteins, 85, 102 Apoptosis, 18, 22, 86

Applicability, 25, 86 Arachidonic Acid, 36, 43, 86, 110 Arginine, 84, 86, 106, 119 Arterial, 7, 8, 16, 84, 86, 88, 90, 100, 101, 111, 117 Arteries, 85, 86, 87, 89, 92, 101, 103, 104, 105, 117 Arterioles, 7, 48, 86, 87, 88, 104 Arteriovenous, 86, 89, 104 Artery, 85, 86, 89, 92, 95, 101, 104, 113 Astigmatism, 86, 112 Asymptomatic, 14, 24, 86 Atmospheric Pressure, 86, 100 Atrophy, 4, 86 Attenuation, 15, 86 Autonomic, 12, 86, 107, 108 Autopsy, 9, 48, 86 B Bacteria, 85, 86, 95, 99, 104, 115, 118 Bactericidal, 86, 96 Bacteriophage, 86, 118 Basal Ganglia, 30, 86, 89, 111 Basement Membrane, 86, 96 Benign, 87, 93 Beta carotene, 44, 87 Beta-pleated, 84, 87 Bile, 87, 102, 116 Bilirubin, 33, 83, 87 Biochemical, 9, 10, 87, 114 Biological Transport, 87, 93 Biomarkers, 10, 20, 87 Biopsy, 9, 87, 108 Biosynthesis, 86, 87, 114 Biotechnology, 21, 22, 52, 63, 87 Bladder, 87, 100, 110, 119 Blood Coagulation, 87, 88, 117 Blood Platelets, 87, 114 Blood pressure, 12, 23, 39, 40, 78, 85, 87, 88, 89, 100, 107, 115 Blood vessel, 5, 7, 15, 17, 49, 85, 87, 88, 90, 95, 101, 102, 108, 115, 116, 117, 119 Blood Volume, 18, 87 Blood-Brain Barrier, 5, 87 Blot, 88, 100 Blotting, Western, 88, 100 Body Fluids, 87, 88, 115, 119 Bone Marrow, 88, 97, 103, 105 Bone scan, 88, 114

122

Hemorrhagic Stroke

Bradykinin, 88, 106, 109 Brain Stem, 12, 88 Bypass, 88, 117 C Calcium, 88, 91, 101, 103, 111 Capillary, 88, 119 Capsules, 88, 97 Captopril, 36, 88 Cardia, 32, 88 Cardiac, 41, 84, 88, 96, 105, 116 Cardiac arrest, 41, 88, 116 Cardiovascular, 8, 10, 11, 40, 42, 44, 88, 102, 114 Cardiovascular disease, 10, 11, 42, 44, 88, 102 Carotene, 44, 87, 89, 113 Carotenoids, 87, 89 Carotid Sinus, 39, 89 Carrier Proteins, 89, 109 Case report, 43, 89 Cause of Death, 19, 89 Cell Death, 86, 89, 106 Cell Division, 86, 89, 105, 109 Cell proliferation, 5, 89 Central Nervous System, 89, 95, 98, 106, 110, 114 Centrifugation, 89, 117 Cerebral Angiography, 89, 103 Cerebral Arteries, 8, 41, 89, 104 Cerebral Cortex, 6, 89, 96 Cerebral hemispheres, 86, 88, 89, 90, 117 Cerebral Hemorrhage, 5, 6, 8, 9, 18, 89 Cerebrospinal, 5, 79, 89, 90 Cerebrospinal fluid, 5, 79, 90 Cerebrovascular, 5, 6, 7, 18, 26, 88, 90 Cerebrum, 89, 90, 117 Chemotactic Factors, 90, 91 Chest wall, 90, 109 Chin, 40, 90, 104 Cholesterol, 30, 32, 52, 87, 90, 92, 102, 103, 116 Cholesterol Esters, 90, 102 Chromatin, 86, 90 Chromosome, 10, 90, 102 Chronic, 5, 7, 12, 29, 48, 90, 100, 116 Chylomicrons, 90, 102 Clinical Medicine, 90, 110 Clinical trial, 4, 13, 63, 90, 94, 111, 112 Cloning, 10, 87, 90 Clot Retraction, 90, 109 Cluster Analysis, 9, 90 Cofactor, 90, 111, 117

Cohort Studies, 9, 91 Collagen, 84, 87, 91, 97, 103, 109 Collapse, 91, 109 Colon, 12, 91 Complement, 6, 84, 91, 98, 109 Complementary and alternative medicine, 39, 46, 91 Complementary medicine, 39, 91 Compress, 92 Compulsions, 92, 107 Computational Biology, 63, 92 Computed tomography, 25, 49, 92, 114 Computerized axial tomography, 92, 114 Computerized tomography, 92 Concomitant, 9, 92 Confounding, 21, 92 Consciousness, 78, 92, 93 Constriction, 8, 92, 101 Contraindications, ii, 92 Contrast Media, 92, 103 Convulsions, 92, 106 Coordination, 78, 92 Coronary, 9, 11, 25, 88, 92, 104, 105 Coronary heart disease, 9, 11, 88, 92 Coronary Thrombosis, 92, 104, 105 Corpuscle, 93, 96 Cortex, 15, 93, 104, 113 Cortical, 8, 48, 93, 96, 114 Criterion, 13, 93 Critical Care, 14, 15, 93 Curative, 93, 117 Cyclic, 83, 93, 98, 106 Cytokine, 11, 93 Cytoplasm, 86, 93, 95, 98, 105, 113, 117 D Danazol, 43, 93 Deletion, 86, 93 Dementia, 4, 93 Dendrites, 93, 106 Density, 14, 89, 93, 102, 107 Detergents, 93, 97 Diagnostic procedure, 47, 52, 93 Diastolic, 93, 100 Diencephalon, 93, 117 Diffusion, 13, 18, 19, 87, 93 Direct, iii, 13, 48, 55, 90, 93, 94, 108, 112, 116 Disinfectant, 93, 96 Disparity, 12, 93 Dopamine, 94, 106, 108 Double-blind, 13, 94 Drug Interactions, 57, 94

123

Drug Tolerance, 94, 118 Duodenum, 87, 94, 95, 116 Dura mater, 94, 104, 107 Dyes, 84, 94 Dysphagia, 32, 94 E Echo-Planar Imaging, 18, 94 Edema, 48, 78, 94 Effector, 91, 94 Efficacy, 13, 16, 43, 94, 118 Electroacupuncture, 43, 94 Electrolyte, 94, 110, 115 Electrons, 94, 101, 103, 107, 112 Elementary Particles, 94, 103, 111 Embolectomy, 19, 95, 117 Embolism, 39, 80, 95, 101 Embolus, 95, 100 Embryo, 10, 95 Endogenous, 94, 95, 96, 106 Endorphins, 95, 106 Endoscope, 95 Endoscopic, 19, 95 Endothelial cell, 8, 17, 87, 95, 117 Endothelium, 95, 106, 109 Endothelium-derived, 95, 106 Endotoxins, 91, 95 Enkephalins, 95, 106 Environmental Health, 62, 64, 95 Enzymatic, 84, 88, 89, 91, 95, 97, 113 Enzyme, 83, 94, 95, 98, 107, 109, 110, 111, 113, 117, 118, 119, 120 Enzyme Inhibitors, 95, 109 Ephedrine, 42, 95 Epidermis, 96, 111 Epinephrine, 83, 94, 96, 106, 119 Erythrocyte Membrane, 30, 96 Erythrocyte Volume, 87, 96 Erythrocytes, 30, 44, 88, 96, 99, 112 Essential Tremor, 15, 96 Ethanol, 41, 48, 96 Euphoria, 48, 96 Evacuation, 19, 96 Evoke, 96, 116 Excitation, 94, 96, 106 Excitatory, 96, 98, 106 Excitatory Amino Acids, 96, 106 Exogenous, 88, 95, 96 Extracellular, 17, 48, 84, 96, 97, 103, 105, 115 Extracellular Matrix, 17, 96, 103 Extracellular Matrix Proteins, 96, 103 Extracellular Space, 96, 97

F Family Planning, 63, 97 Fat, 40, 85, 86, 87, 88, 89, 92, 95, 97, 102, 107, 119 Fibril, 14, 97 Fibrinogen, 11, 42, 97, 109, 117 Fibrinolytic, 11, 97, 117 Fibrinolytic Agents, 97, 117 Filler, 14, 97 Fish Oils, 40, 97 Fold, 19, 97 Forearm, 87, 97 Fractionation, 97, 117 Frontal Lobe, 30, 97 G Gas, 84, 93, 97, 99, 106, 109, 119 Gastrointestinal, 88, 96, 97, 114, 116, 119 Gastrointestinal tract, 96, 97, 114, 119 Gene, 4, 6, 9, 10, 15, 20, 31, 87, 97, 98 Gene Expression, 9, 20, 97 Gene Therapy, 15, 97 Genetic Engineering, 87, 90, 98 Genetics, 4, 5, 10, 21, 98 Genomics, 17, 98 Genotype, 14, 18, 98, 108 Gland, 83, 98, 107, 110, 116, 118 Globus Pallidus, 98, 112 Glucocorticoid, 29, 98 Glucose, 98, 99, 101 Glutamic Acid, 98, 106 Glycine, 84, 98, 106, 114 Glycoprotein, 25, 97, 98, 117 Glycosaminoglycans, 13, 97, 98 Governing Board, 98, 110 Grade, 11, 98 Granulocytes, 98, 120 Guanylate Cyclase, 98, 106 H Heart attack, 88, 98 Heart failure, 95, 99 Heartbeat, 99, 116 Hematoma, 27, 99 Heme, 27, 33, 87, 99, 107 Hemoglobin, 96, 99 Hemoglobinopathies, 98, 99 Hemolysis, 96, 99 Hemorrhage, 6, 8, 9, 11, 13, 16, 17, 18, 19, 20, 21, 29, 48, 49, 99, 111, 116 Hemostasis, 5, 99, 114 Hereditary, 5, 6, 18, 99 Heredity, 97, 98, 99 Homeostasis, 18, 99

124

Hemorrhagic Stroke

Homologous, 97, 99, 116 Hormonal, 86, 99 Hormone, 96, 99, 101, 118 Hybrid, 10, 99 Hydration, 15, 99 Hydrogen, 84, 96, 99, 105, 107, 111 Hydrophobic, 93, 99, 102 Hyperbaric, 41, 100 Hyperbaric oxygen, 100 Hyperopia, 100, 112 Hyperoxia, 41, 100 Hypertension, 12, 28, 29, 33, 36, 88, 89, 100 Hypotension, 43, 92, 100 Hypoxia, 48, 100 I Idiopathic, 43, 100 Immune response, 85, 100, 116, 119 Immune system, 100, 103, 120 Immunoblotting, 8, 100 Immunoglobulins, 100, 109 Immunosuppressive, 28, 43, 98, 100 Immunosuppressive therapy, 28, 43, 100 Impairment, 4, 49, 100 In vitro, 12, 19, 42, 97, 100 In vivo, 19, 48, 97, 100, 117 Incision, 100, 101 Incontinence, 78, 95, 100 Infancy, 28, 100 Infarction, 11, 40, 48, 89, 100, 101, 113 Infection, 26, 90, 100, 103, 116, 120 Inflammation, 11, 83, 85, 101, 104, 107, 109, 113, 119 Ingestion, 26, 101 Insight, 10, 101 Insulin, 10, 101 Insulin-dependent diabetes mellitus, 101 Intracellular, 12, 100, 101, 106, 110, 112 Intracranial Aneurysm, 14, 20, 21, 89, 101 Intracranial Arteriosclerosis, 89, 101 Intravascular, 9, 101 Intravenous, 13, 80, 101 Intrinsic, 14, 83, 87, 101 Invasive, 15, 16, 19, 49, 101, 103 Involuntary, 96, 101, 105 Ions, 94, 99, 101, 110 Ischemia, 8, 13, 17, 29, 48, 86, 101, 106, 113 Ischemic stroke, 6, 9, 13, 16, 19, 20, 21, 29, 42, 49, 52, 101 K Kb, 62, 101 Kidney Transplantation, 26, 102

L Labile, 91, 102 Least-Squares Analysis, 102, 113 Lenses, 100, 102, 112 Lesion, 5, 102 Leukemia, 98, 102 Leukocytes, 88, 90, 98, 102, 105 Ligament, 102, 110 Likelihood Functions, 102, 113 Linear Models, 102, 113 Linkages, 98, 99, 102 Lipid, 86, 101, 102 Lipoprotein, 31, 102, 103 Lipoprotein(a), 31, 102 Liver, 80, 83, 84, 86, 87, 97, 102, 113, 114 Liver scan, 102, 114 Localization, 10, 102 Localized, 84, 99, 100, 102, 109 Logistic Models, 103, 113 Low-density lipoprotein, 102, 103 Lymph, 93, 95, 103 Lymphatic, 95, 101, 103, 115 Lymphocyte, 85, 103 M Magnetic Resonance Angiography, 17, 103 Magnetic Resonance Imaging, 13, 16, 30, 49, 94, 103, 108, 114 Magnetic Resonance Spectroscopy, 30, 103 Malformation, 5, 103 Malnutrition, 83, 86, 103 Mass Screening, 30, 103 Matrix metalloproteinase, 17, 103 Mediator, 8, 103, 114 MEDLINE, 63, 103 Medullary, 103, 112 Melanin, 103, 108, 119 Membrane, 91, 104, 107, 108, 110, 111, 113, 117 Memory, 78, 93, 104 Meninges, 89, 94, 104 Meningitis, 27, 104 Mental, iv, 4, 8, 43, 48, 62, 64, 89, 90, 93, 104, 111 Mental Health, iv, 4, 62, 64, 104, 111 Mentors, 17, 104 Meta-Analysis, 24, 104 Metabolite, 33, 104 Metastasis, 103, 104 MI, 11, 81, 104 Microbe, 104, 118

125

Microcirculation, 7, 48, 104, 109 Microorganism, 90, 104, 120 Middle Cerebral Artery, 16, 104 Migration, 5, 104 Mitochondrial Swelling, 104, 106 Mitogen-Activated Protein Kinase Kinases, 104, 105 Mitogen-Activated Protein Kinases, 41, 104 Mitosis, 86, 105 Modification, 8, 84, 98, 105, 112 Molecular, 4, 5, 8, 10, 17, 21, 63, 65, 87, 92, 97, 105, 109, 112, 118 Molecule, 13, 18, 85, 91, 94, 95, 96, 99, 105, 107, 112, 119 Monoclonal, 100, 105 Monoclonal antibodies, 100, 105 Monocytes, 5, 102, 105 Mononuclear, 105 Morphological, 95, 105 Morphology, 5, 7, 105 Motility, 105, 114 Myelin, 16, 105 Myocardial infarction, 11, 22, 26, 92, 104, 105 Myocardium, 104, 105 Myopia, 105, 112 N Narcolepsy, 95, 105 Necrosis, 18, 86, 100, 104, 105, 113 Neostriatum, 106, 112 Nerve, 83, 85, 90, 93, 103, 106, 107, 110, 116, 117, 118 Nerve Endings, 106, 117 Nervous System, 89, 103, 106, 108, 116 Neural, 12, 43, 84, 106 Neurologic, 14, 16, 20, 21, 106 Neurology, 13, 17, 19, 27, 28, 29, 34, 39, 44, 106 Neuronal, 12, 19, 106 Neurons, 6, 12, 93, 96, 106, 116 Neuroprotective Agents, 13, 106 Neuropsychological Tests, 4, 106 Neurotransmitter, 12, 84, 88, 94, 96, 98, 106, 107, 116 Nitric Oxide, 7, 106 Nitrogen, 84, 96, 106, 119 Norepinephrine, 42, 83, 94, 95, 106, 108 Normotensive, 23, 107 Nuclear, 86, 94, 106, 107, 117 Nuclei, 15, 84, 94, 97, 98, 103, 105, 107, 111

Nucleus, 86, 90, 93, 95, 98, 105, 106, 107, 111, 112, 117 O Obsessive-Compulsive Disorder, 15, 107 Omega-3 fatty acid, 42, 107 Opacity, 93, 107 Organelles, 89, 93, 105, 107 Oxidation, 85, 107 Oxygenase, 27, 33, 107 Oxygenation, 107 P Pachymeningitis, 104, 107 Palliative, 107, 117 Pancreas, 87, 101, 107, 119 Paralysis, 8, 107 Paramedic, 20, 107 Particle, 107, 118 Pathogenesis, 7, 9, 17, 107 Pathologic, 13, 86, 87, 92, 108 Pathologic Processes, 86, 108 Pathophysiology, 10, 13, 18, 19, 108 Pelvic, 108, 110 Peptide, 5, 13, 17, 19, 84, 108, 109, 110, 111 Percutaneous, 25, 108 Perfusion, 13, 18, 19, 48, 100, 108 Perfusion magnetic resonance imaging, 13, 108 Peripheral Nervous System, 95, 106, 108, 116 Pharmacologic, 15, 85, 108, 118 Phenotype, 5, 108 Phenylalanine, 108, 119 Phenylpropanolamine, 3, 22, 31, 34, 45, 108 Phospholipids, 97, 102, 108, 111 Phosphorus, 88, 108 Phosphorylation, 12, 105, 108, 111 Physiologic, 13, 83, 87, 108, 112 Physiology, 5, 7, 43, 108 Pigment, 87, 108 Pilot study, 13, 109 Plants, 98, 105, 107, 109, 118 Plasma, 6, 10, 17, 31, 42, 83, 87, 90, 97, 99, 102, 109, 113, 114 Plasma protein, 17, 83, 109 Plasma Volume, 87, 109 Plasmin, 11, 97, 109, 118, 119 Plasminogen, 97, 109, 118, 119 Plasminogen Activators, 109 Platelet Activation, 43, 109 Platelet Aggregation, 84, 106, 109, 117 Platelets, 106, 109, 117

126

Hemorrhagic Stroke

Platinum, 14, 109 Pneumonia, 92, 109 Pneumothorax, 14, 109 Polymorphism, 23, 27, 31, 109 Polypeptide, 84, 91, 97, 109 Pons, 88, 110 Postoperative, 14, 110 Post-synaptic, 110, 117 Potassium, 7, 110, 115 Potassium Channels, 7, 110 Practicability, 110, 119 Practice Guidelines, 64, 110 Precursor, 6, 17, 18, 27, 86, 87, 94, 95, 106, 108, 109, 110, 119 Prenatal, 95, 110 Presynaptic, 106, 110 Probe, 15, 110 Progression, 18, 85, 110 Progressive, 93, 94, 105, 109, 110 Projection, 18, 107, 110 Prone, 12, 36, 44, 110 Prospective study, 24, 32, 110 Prostaglandins, 86, 110 Prostate, 12, 87, 110, 119 Protease, 17, 110, 118 Protein C, 83, 85, 86, 102, 111 Protein Kinase C, 104, 105, 111 Protein S, 87, 111, 113 Proteins, 6, 10, 12, 16, 44, 84, 85, 86, 88, 89, 90, 91, 96, 103, 105, 106, 108, 109, 111, 112, 114 Protein-Serine-Threonine Kinases, 104, 111 Proteolytic, 91, 97, 109, 111, 118, 119 Protocol, 18, 111 Protons, 99, 103, 111, 112 Psychiatric, 4, 6, 16, 111 Psychiatry, 111, 116 Psychic, 104, 111, 114 Public Health, 9, 20, 21, 64, 111 Public Policy, 63, 111 Publishing, 21, 111 Pulmonary, 87, 111, 119 Pulmonary Artery, 87, 111, 119 Purpura, 43, 111 Putamen, 28, 106, 111 Q Quality of Life, 39, 112 R Race, 7, 104, 112 Radar, 15, 112 Radiation, 95, 97, 100, 103, 112, 114, 120

Radioactive, 88, 99, 102, 105, 107, 112, 114 Radiological, 21, 108, 112 Radiology, 13, 18, 112 Randomized, 13, 14, 19, 24, 94, 112 Randomized Controlled Trials, 24, 112 Receptor, 5, 11, 12, 85, 94, 111, 112, 114 Receptors, Serotonin, 112, 114 Recombinant, 18, 112, 119 Recombination, 97, 112 Rectum, 85, 91, 97, 100, 110, 112 Recurrence, 14, 112 Red blood cells, 96, 107, 112 Refer, 1, 91, 95, 102, 112, 118 Refraction, 49, 105, 112, 115 Regimen, 94, 112, 113 Regression Analysis, 4, 113 Remission, 112, 113 Renin, 88, 113 Renin-Angiotensin System, 88, 113 Reperfusion, 18, 113 Reperfusion Injury, 113 Retinal, 93, 113 Retreatment, 20, 113 Retrospective, 11, 20, 113 Retroviral vector, 97, 113 Rhinitis, 95, 113 Ribosome, 113, 118 Risk factor, 5, 11, 20, 23, 28, 30, 32, 42, 52, 103, 110, 114 S Scans, 14, 15, 114 Screening, 48, 90, 114 Seizures, 4, 10, 52, 79, 114 Semen, 110, 114 Sensor, 15, 114 Sequencing, 10, 114 Serine, 104, 111, 114, 118 Serotonin, 8, 106, 112, 114, 119 Serum, 10, 16, 20, 30, 32, 33, 83, 84, 91, 103, 114 Sex Characteristics, 83, 114 Shock, 41, 42, 114, 118 Side effect, 55, 83, 114, 118 Skull, 114, 117 Smooth muscle, 5, 84, 113, 115, 116 Soaps, 97, 115 Social Environment, 112, 115 Social Security, 11, 112, 115 Sodium, 18, 115 Solvent, 96, 115 Soma, 115 Somatic, 5, 83, 105, 108, 115

127

Specialist, 69, 115 Species, 96, 99, 104, 105, 112, 115, 119, 120 Specificity, 12, 17, 83, 115 Spectrum, 16, 21, 115 Sperm, 90, 115 Spinal cord, 88, 89, 90, 94, 104, 106, 107, 108, 115 Spleen, 84, 103, 115 Splenectomy, 43, 115 Staging, 14, 114, 115 Stasis, 40, 115 Steroid, 93, 116 Stimulus, 15, 96, 116, 117 Stomach, 88, 97, 99, 115, 116 Stool, 56, 91, 100, 116 Stress, 33, 105, 116 Stupor, 48, 116 Subacute, 33, 100, 116 Subarachnoid, 8, 21, 29, 48, 116 Subclinical, 11, 100, 114, 116 Subcutaneous, 94, 116 Substance P, 104, 116 Sudden death, 48, 116 Supplementation, 44, 116 Supratentorial, 27, 116 Sympathomimetic, 94, 96, 107, 108, 116 Symphysis, 90, 110, 116 Symptomatic, 14, 116 Synapse, 83, 110, 116, 118 Synaptic, 106, 116 Synaptosomes, 12, 117 Systemic, 84, 87, 96, 101, 117 Systolic, 100, 117 T Telencephalon, 86, 89, 117 Temporal, 7, 84, 117 Thalamic, 41, 117 Thalamus, 28, 93, 117 Therapeutics, 42, 48, 57, 117 Threshold, 15, 18, 100, 117 Thrombectomy, 9, 95, 117 Thrombin, 97, 109, 111, 117 Thrombolytic, 17, 22, 109, 117 Thrombolytic Therapy, 17, 22, 117 Thrombomodulin, 32, 111, 117 Thromboplastin, 80, 117 Thrombosis, 32, 101, 111, 116, 117 Thromboxanes, 86, 117 Thrombus, 9, 92, 100, 101, 109, 117 Thyroid, 118, 119

Tissue Plasminogen Activator, 6, 16, 18, 22, 118 Tolerance, 29, 36, 118 Tomography, 15, 33, 103, 118 Tone, 107, 118 Topical, 96, 115, 118 Torsion, 100, 118 Toxic, iv, 6, 96, 118 Toxicity, 14, 94, 118 Toxicology, 64, 118 Toxin, 118 Transduction, 12, 118 Transfection, 87, 97, 118 Translation, 4, 84, 118 Translocation, 12, 118 Transmitter, 49, 94, 96, 103, 107, 118 Trauma, 11, 15, 42, 89, 106, 118 Treatment Outcome, 20, 118 Tryptophan, 91, 114, 119 Tumor marker, 87, 119 Tyrosine, 41, 94, 119 U Unsaturated Fats, 97, 119 Urethra, 110, 119 Urinary, 95, 100, 118, 119 Urinary Plasminogen Activator, 118, 119 V Vascular, 4, 5, 7, 10, 17, 36, 84, 89, 95, 100, 101, 103, 104, 106, 109, 117, 119 Vasculitis, 28, 119 Vasodilatation, 89, 119 Vasodilator, 8, 88, 94, 119 VE, 16, 119 Vector, 118, 119 Vein, 85, 86, 101, 107, 119 Ventricle, 84, 111, 117, 119 Venules, 48, 87, 88, 104, 119 Veterinary Medicine, 63, 119 Viral, 118, 119 Virulence, 118, 119 Virus, 86, 98, 113, 118, 119 Viscera, 115, 119 Vitro, 120 Vivo, 19, 120 W White blood cell, 6, 85, 102, 103, 120 Wound Healing, 103, 120 X Xenograft, 85, 120 X-ray, 14, 92, 107, 112, 114, 120 Y Yeasts, 108, 120

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