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

PULMONARY EMBOLISM A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES J...

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PULMONARY EMBOLISM 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., 1960Pulmonary Embolism: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-84569-7 1. Pulmonary Embolism-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 pulmonary embolism. 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 PULMONARY EMBOLISM........................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Pulmonary Embolism ................................................................... 4 E-Journals: PubMed Central ....................................................................................................... 24 The National Library of Medicine: PubMed ................................................................................ 25 CHAPTER 2. NUTRITION AND PULMONARY EMBOLISM ................................................................. 71 Overview...................................................................................................................................... 71 Finding Nutrition Studies on Pulmonary Embolism .................................................................. 71 Federal Resources on Nutrition ................................................................................................... 74 Additional Web Resources ........................................................................................................... 74 CHAPTER 3. CLINICAL TRIALS AND PULMONARY EMBOLISM ....................................................... 75 Overview...................................................................................................................................... 75 Recent Trials on Pulmonary Embolism ....................................................................................... 75 Keeping Current on Clinical Trials ............................................................................................. 77 CHAPTER 4. PATENTS ON PULMONARY EMBOLISM ....................................................................... 79 Overview...................................................................................................................................... 79 Patents on Pulmonary Embolism ................................................................................................ 79 Patent Applications on Pulmonary Embolism........................................................................... 100 Keeping Current ........................................................................................................................ 108 CHAPTER 5. BOOKS ON PULMONARY EMBOLISM ......................................................................... 109 Overview.................................................................................................................................... 109 Book Summaries: Online Booksellers......................................................................................... 109 Chapters on Pulmonary Embolism ............................................................................................ 110 CHAPTER 6. PERIODICALS AND NEWS ON PULMONARY EMBOLISM ........................................... 113 Overview.................................................................................................................................... 113 News Services and Press Releases.............................................................................................. 113 Academic Periodicals covering Pulmonary Embolism............................................................... 116 CHAPTER 7. RESEARCHING MEDICATIONS .................................................................................. 117 Overview.................................................................................................................................... 117 U.S. Pharmacopeia..................................................................................................................... 117 Commercial Databases ............................................................................................................... 120 Researching Orphan Drugs ....................................................................................................... 120 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 125 Overview.................................................................................................................................... 125 NIH Guidelines.......................................................................................................................... 125 NIH Databases........................................................................................................................... 127 Other Commercial Databases..................................................................................................... 129 APPENDIX B. PATIENT RESOURCES ............................................................................................... 131 Overview.................................................................................................................................... 131 Patient Guideline Sources.......................................................................................................... 131 Finding Associations.................................................................................................................. 146 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 149 Overview.................................................................................................................................... 149 Preparation................................................................................................................................. 149 Finding a Local Medical Library................................................................................................ 149 Medical Libraries in the U.S. and Canada ................................................................................. 149 ONLINE GLOSSARIES................................................................................................................ 155 Online Dictionary Directories ................................................................................................... 157

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PULMONARY EMBOLISM DICTIONARY............................................................................. 159 INDEX .............................................................................................................................................. 215

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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 pulmonary embolism 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 pulmonary embolism, 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 pulmonary embolism, 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 pulmonary embolism. 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 pulmonary embolism, 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 pulmonary embolism. 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 PULMONARY EMBOLISM Overview In this chapter, we will show you how to locate peer-reviewed references and studies on pulmonary embolism.

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

Chronic Dialysis Patients Have High Risk for Pulmonary Embolism Source: American Journal of Kidney Diseases. 39(5): 1011-1017. May 2002. Contact: Available from W.B. Saunders Company. Periodicals Department, 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452 or (407) 345-4000. Summary: Pulmonary embolism (a blood clot in the lungs) has been considered uncommon in chronic dialysis patients, but has not been adequately studied in a large population. In the United States Renal Data System (USRDS), 76,718 patients presenting with end stage renal disease (ESRD) between January 1996 and December 1996 were analyzed in a historical cohort study. The outcome was hospitalizations with a primary discharge diagnosis of pulmonary embolism occurring within 1 year of the first ESRD

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treatment and excluding those occurring after renal (kidney) transplantation. For dialysis patients, hospitalization rates for pulmonary embolism were obtained from the National Hospital Discharge Survey for 1996. In 1996, the overall incidence rate of pulmonary embolism was 149.90 per 100,000 dialysis patients compared with 24.62 per 100,000 persons in the U.S. population, with an age adjusted incidence ratio of 2.34 in dialysis patients. Younger dialysis patients had the greatest relative risk for pulmonary embolism. The age-adjusted incidence ratio of pulmonary embolism after excluding dialysis patients with known risk factors for pulmonary embolism was 2.11. Ninety-five percent confidence intervals for all age categories in both models were statistically significant. The authors conclude that chronic dialysis patients have high risk for pulmonary embolism, independent of comorbidity (the presence of other illnesses). 2 tables. 37 references.

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

Project Title: ANTITHROMBOTIC GLYCOSAMINOGLYCANS

ACTIVITY

OF

ASCIDIAN

Principal Investigator & Institution: Tollefsen, Douglas M.; Professor; Internal Medicine; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 01-JAN-2002; Project End 31-DEC-2004 Summary: (provided by applicant) Heparin from porcine or bovine tissues is used to treat diseases such as venous thrombosis, pulmonary embolism, and coronary artery thrombosis. The anticoagulant effects of heparin result from binding to antithrombin and heparin cofactor II (HCII), which are thereby activated to inhibit thrombin and other coagulation enzymes. Dermatan sulfate is a related polymer that specifically activates HCII. Dermatan sulfates and heparin isolated from the marine invertebrates Styela plicata and Ascidia nigra differ from mammalian glycosaminoglycans in the degree and position of sulfation. These differences have profound effects on their anticoagulant properties in vitro, including their ability to activate antithrombin and HCII. In the present study, ascidian glycosaminoglycans will be compared with their mammalian 2

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

Studies

5

counterparts to determine the relative contributions of HCII and antithrombin to the antithrombotic activities of heparin and dermatan sulfate. The specific aims are as follows: (1) Prepare low molecular weight derivatives of ascidian glycosaminoglycans, characterize their structures by nuclear magnetic resonance spectroscopy, and determine their anticoagulant activities in vitro. (2) Compare the anticoagulant properties of ascidian dermatan sulfate and heparin with their low molecular weight derivatives in vivo. (3) Investigate the antithrombotic activity of the ascidian glycosaminoglycans in experimental venous and arterial thrombosis models in rats and in normal or HCII-deficient mice. (4) Study the effects of the ascidian glycosaminoglycans and their low molecular weight derivatives on platelet function and determine the hemorrhagic effects of these polymers in vivo. These studies will provide insight into the antithrombotic mechanisms of glycosaminoglycans and may lead to development of anticoagulants with fewer side effects, improved pharmacokinetics, or greater potency than standard heparin preparations. This research will be done primarily in Brazil as an extension of NIH grant 5 R0l HL 55520-05. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CIRCADIAN ROLE IN DIURNAL PATTERN OF CARDIOVASCULAR RISK Principal Investigator & Institution: Stanley, H Eugene.; Physics; Boston University Charles River Campus 881 Commonwealth Avenue Boston, Ma 02215 Timing: Fiscal Year 2002; Project Start 10-SEP-2002; Project End 30-JUN-2004 Summary: (provided by applicant): Numerous epidemiological studies demonstrate that sudden cardiac death, pulmonary embolism, myocardial infarction, and stroke have a 24-hour daily pattern with a broad peak between 9:00 to 11:00 AM. The mechanisms underlying this daily pattern are unknown. As an important first step to elucidate mechanisms, we propose an innovation that combines circadian cardiovascular physiology with analysis of a unique existing data set using novel statistical approaches that we have developed and shown to be sensitive indicators of cardiac dynamics and cardiac risk. Our primary mechanistic aim is to distinguish the separate effects upon cardiac dynamics of (i) the intrinsic circadian rhythm and (ii) the daily pattern in behavior related to the sleep-wake cycle and activity level. We will analyze existing data sets of four physiologically related variables (heart rate, blood pressure, temperature and activity level) that were simultaneously recorded in ostensibly healthy individuals throughout two complementary circadian protocols in which subjects' behaviors (including activity level and sleep-wake cycle) are controlled and the environment is constant. The protocols were: (i) a 10day Forced Desynchrony protocol (wherein subjects' sleep-wake cycles are adjusted to 28 hours so that their behaviors occur across all circadian phases) and (ii) a 38 hour constant routine protocol (wherein subjects remain awake and semi-recumbent). Core body temperature will be used as a circadian phase marker. From these data we will extract complementary statistical indices of dynamical structure and synchronization with our novel and sensitive analysis tools: (i) Detrended Fluctuation Analysis; (ii) Magnitude and Sign Analysis; (iii) Wavelet Transform; (iv) Hilbert Transform; (v) Fractal and Multifractal Analysis; (vi) Phase Synchronization Analysis. Analyses of these statistics in relation to the phase of the circadian rhythm, or separately the behavioral pattern may reveal cardiac dynamics related to the daily pattern of cardiovascular vulnerability. Furthermore, analysis of synchronization patterns among the physiologically related variables will enable us to deduce mechanistic links among variables that could underlie the cardiac dynamics.

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Our future aim (beyond this application) would be to determine whether the results in healthy individuals relate to patients with known cardiovascular risk. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INHIBITOR

DEVELOPMENT

OF

AN

ANTIDOTE-CONTROLLED

FIXA

Principal Investigator & Institution: Rusconi, Christopher P.; Regado Biosciences, Inc. 7030 Kit Creek Rd, Ste 250 Morrisville, Nc 27560 Timing: Fiscal Year 2004; Project Start 15-JAN-2004; Project End 14-JUL-2004 Summary: (provided by applicant): Anticoagulant therapy is required to perform a number of clinical procedures including coronary artery bypass graft (CABG) surgery and other "open-heart" surgeries, percutaneous coronary interventions (PCI, "angioplasties"), and dialysis; and is also used as a treatment for a number of thrombotic diseases including acute coronary syndromes (heart attacks and unstable angina), deep vein thrombosis, pulmonary embolism, and peripheral vascular disease. The major toxicity and limitation of anticoagulant therapy is serious drug-induced bleeding. For example, transfusions due to blood loss are required in upwards of 50 percent of CABG surgeries and 10-15 percent of PCI procedures. Thus, there is a critical need for safer anticoagulants, particularly agents whose activity can be readily controlled, to reduce the number and magnitude of such bleeding events. Regado Biosciences, Inc. is addressing this unmet need by developing the first generation of regulatable (i.e., antidote-controlled) therapeutics. In Regado's Regulatable Drug Discovery Platform, the drug is comprised of a nucleic acid aptamer, and the antidote is comprised of an oligonucleotide that is complementary to a portion of the drug. The Company's primary focus is the discovery and development of antidote-controlled antithrombotics, and its lead drug discovery program is its Regulatable Anticoagulants Program. The Company is currently developing an antidote-controlled antagonist, REG1 and its matched antidote, REG1 AD, against coagulation factor IXa (FlXa) for use in open-heart surgeries and angioplasties. In 2000, there were more than 500,000 CABG surgeries and greater than 1,000,000 PCI procedures performed in the U.S., and FIXa is a validated target for anticoagulant development for these indications. The REG1 drug-antidote pair has been validated in the test tube and in patient plasma samples (Rusconi et al, Nature 419, p. 90-94, 2002), and more recently in a small-animal model of arterial thrombosis and in small and large animal models of anticoagulation and drug neutralization (see preliminary data). While the REG1 drug-antidote pair has performed well in these studies, REG1 has not been fully stabilized to prevent its degradation by bodily endonucleases, nor has it been fully minimized to enable more cost-effective manufacturing. Therefore, in its current form, REG1 may require higher doses to maintain a needed biologic effect over time and have higher manufacturing costs as compared to a fully optimized compound. Our Overall Goal is to fully optimize the REG1 drug-antidote pair to generate candidate compounds for preclinical and clinical testing. The Specific Aims of this proposal are 1) To optimize the coagulation FlXa inhibitor REG1, leading to the selection of a preclinical/clinical candidate anticoagulant and 2) To optimize the neutralization activity of the antidote for REG1, leading to the selection of a preclinical/clinical candidate REG1 antidote. Completion of the experiments proposed will position the Company to initiate IND-enabling non-clinical studies and ultimately human clinical studies with fully optimized candidate compounds. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

Studies

•

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Project Title: EICOSANOIDS AND PULMONARY VASCULAR TONE Principal Investigator & Institution: Pfister, Sandra L.; Pharmacology and Toxicology; Medical College of Wisconsin Po Box26509 Milwaukee, Wi 532260509 Timing: Fiscal Year 2002; Project Start 01-JAN-1998; Project End 31-DEC-2003 Summary: (Applicant's abstract): In recent years, the importance of various factors synthesized and released from the blood vessel endothelium that contribute to the regulation of vascular tone has become apparent. In pulmonary vessels, these investigators have identified an endothelium-dependent contracting factor as the vasoconstrictor thromboxane A2. There are a number of incidences where an increased synthesis of thromboxane A2 is associated with pulmonary disease, including pulmonary hypertension and sudden death. Therefore, the long term objective of the proposed studies is to investigate the hypothesis that arachidonic acid is metabolized by pulmonary blood vessels to thromboxane A2 and that thromboxane A2 is an important mediator involved in the regulation of pulmonary vascular tone under both normal and pathophysiological states. Specifically, it is known that arachidonic acid and methacholine-induced contractions of pulmonary arteries are mediated by thromboxane A2 and removal of the endothelial layer abolishes the contractions. Yet, endothelial cells isolated from pulmonary arteries do not synthesize thromboxane A2. Experiments described by specific aim 1 will investigate the hypothesis that thromboxane A2 synthesis in pulmonary vessels requires the interaction between the endothelial cells and adherent cells. Possible candidates for the adherent cells include platelets, polymorphonuclear leukocytes or monocytes. Studies have shown that thromboxane A2-induced platelet aggregation and vascular smooth muscle vasoconstriction is mediated via activation of a membrane-bound receptor. One limitation to studying the role of thromboxane A2 in pulmonary disease is the inability to differentiate the contribution of the platelet and the vascular smooth muscle receptor to the observed hemodynamic responses because the available thromboxane receptor antagonists are unfortunately non-selective and block both the platelet and vascular receptors. The investigators have identified a subset of rabbits that are deficient in vascular, but not platelet, thromboxane A2 receptors. Experiments described by specific aim 2 will use these rabbits to investigate the hypothesis that thromboxane A2 and its vascular receptor are important to the regulation of pulmonary vascular tone. Specifically, they will investigate the influence of age and gender on the vascular responsiveness to thromboxane agonist and thromboxane A2 receptor density, characterize the differences in receptor number and functional responses in vascular cells cultured from responder and nonresponder pulmonary arteries and assess the role of the vascular thromboxane A2 receptor in a model of pulmonary embolism. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EPIDEMIOLOGY OF VENOUS THROMBOSIS AND PULMONARY EMBOLISM Principal Investigator & Institution: Folsom, Aaron R.; Professor; Epidemiology; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2003; Project Start 01-FEB-1998; Project End 31-DEC-2006 Summary: (provided by applicant): Venous thromboembolism (VTE), comprising deep venous thrombosis and pulmonary embolism, is a major contributor to morbidity and mortality in the US. We propose here a 4-year continuation of our unique and informative Longitudinal Investigation of Thromboembolism Etiology (LITE), a prospective study within the ARIC and CHS cohorts. We have several important

8

Pulmonary Embolism

findings from the previous project period, the three most important being (1) identification for the first time in a prospective study that plasma fibrin fragment Ddimer, a marker of fibrin turnover, is positively and strongly associated with risk of future VTE, (2) verification, again for the first time prospectively, that factor VIII and von Willebrand factor are strong risk factors for VTE, and (3) demonstration that obesity and diabetes are important VTE risk factors, but that most other arterial disease risk factors, including fibrinogen and C-reactive protein, are not. We plan to build upon these findings during LITE continuation, by adding new cases and testing new hypotheses. Our aims are 1. To extend VTE event follow-up in the LITE Study for 4 more years, which is expected to increase the current number of VTE events (n=335) by 47 percent (to n=493), and to sample 1 control per case. In the new cases and controls, we will measure analytes found to be important in LITE already (factor V Leiden, prothrombin G20210A variant, D-dimer, and TAFI), to serve as covariates in combined analyses. 2. To conduct nested case-control studies in the entire sample of 493 VTE cases and 828 controls, using prediagnosis blood and DNA specimens, to determine the prospective associations of VTE with several novel plasma hemostatic factors and genetic markers. 3. To conduct longitudinal analyses of VTE incidence and potential risk factors (or interaction) that we have not yet fully explored: diet, frailty, hormone replacement therapy, and obesity interactions. 4. To study serial blood levels of Ddimer and homocysteine, to better understand their associations with VTE occurrence. Continuation of this comprehensive prospective study will provide additional important epidemiologic insights into the etiology of VTE. This could lead to new strategies for prevention or treatment of VTE. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HEME OXYGENASE-1 IN LUNG ISCHEMIA-REPERFUSION INJURY Principal Investigator & Institution: Lee, Patty J.; Internal Medicine; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 29-FEB-2008 Summary: (provided by applicant): Oxidant injury is a major contributor to the pathogenesis of many disease processes including acute lung injury. Anoxiareoxygenation (A-R) In cells and ilschemia-reperfusion (I-R) in lungs are common models of oxidant injury. Lung I-R is likely the inciting injury during lung transplantation/surgery, thromboembolectomy, pulmonary embolism, and reexpansion pulmonary edema. These disorders have high mortalities with limited therapeutic options. This is largely due to our limited knowledge of underlying pathogenesis. We also lack appreciation of the degree to which regulatory events in vitro (A-R) are predictive of the events in vivo (I-R). Heme oxygenase (HO) catalyzes the initial and rate-limiting step in the oxidative degradation of heme to biliverdin with generation of carbon monoxide (CO) and iron. A variety of oxidant stressors strongly induce expression of HO-1, an inducible isoform of HO. Studies from our laboratory and others have demonstrated that HO-1 can protect against oxidant-induced lung injury. However, the ability of HO-1 to confer protection and the processes regulating its production in this setting has not been adequately addressed. In addition, the pivotal cell-type responsible for HO-1-mediated protection against oxidant lung injury is unknown. To begin to understand the processes that regulate A-R/I-R we examined the effects of HO-1 in these injury models. We have demonstrated that HO-1 is markedly induced in endothelial cells and mouse lung after A-R/I-R. In addition, the mitogenactivated protein kinases (MAPKs) are responsible for A-R-induced HO-1 expression. We now show that HO-1 overexpression significantly diminishes A-R/I-R-induced

Studies

9

apoptosis in cultured lung endothelial cells and in mouse lung. Our data has led us to propose the following hypotheses: 1) in A-R, HO-1 is induced via novel activation pathways that involve MAPKs and cooperative transcription factor interactions; 2) in IR, similar pathways are activated and are cytoprotective; and 3) in I-R, p38 MAPK activation of endothelial cell HO-1 is a critical event in cytoprotection. To test these hypotheses we will: 1) characterize the cis- and trans-acting elements that mediate HO-1 induction and define the consequences in vitro; 2) determine whether A-R regulates the relevant transcription factors via p38 or JNK MAPKs and define the consequences in vitro; 3) determine whether the processes identified in Aims I and 2 are important in vivo; and 4) define the role of endothelial cell p38 MAPK and HO-1 in HO-1-mediated cytoprotection in vivo. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HOMOCYST(E)INE RESPONSE TO CEREAL FORTIF W/ FOLIC ACID Principal Investigator & Institution: Malinow, M R.; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2002 Summary: Numerous observational studies have shown that an elevated level of total plasma (tHCY) is an independent risk factor for arterial occlusive disease, and is associated with venous thrombosis and pulmonary embolism. Moreover, we have reported that experimental elevation of tHCY in nonhuman primates shows acetycholine-induced arterial relaxation, indicating that elevated tHCY alters vascular function. In the majority of cases, elevated tHCY levels are lowered by treatment with supplemental folic acid. On January 1, 1998, due to such folic acid as known to reduce the risk for neural tube defects (NTD) in the developing fetus, the FDA recommended the fortification of certain foods with folic acid by ~100 ?g/day. Further, to test this hypothesis that nationwide fortification of food with folic acid might reduce tHCY, Malinow et al. conducted a clinical trial using breakfast cereal fortified with different levels of folic acid. Results indicated that such cereals containing folic acid (499 ?g and 655 ?g per 30 g of cereal) lowered similarly tHCY in subjects with coronary heart disease, suggesting that ~400 ?g of folic acid provides maximum effect to lower tHCY. The above study will determine whether folic acid fortification (40 ?g/day) has similar effects as supplementation (2.5 mg/day). In a metanalysis, it has been shown that folic acid supplementation between 0.5 and 5.0 mg/day have similar effects on tHCY levels. FUNDING Homocyst(e)ine testing funds PUBLICATIONS None Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: IMAGING THROMBOEMBOLISM WITH FIBRIN AVID TC-99MPEPTIDE Principal Investigator & Institution: Thakur, Mathew L.; Professor of Radiology; Palatin Technologies, Inc. 214 Carnegie Center, Ste 100 Princeton, Nj 08540 Timing: Fiscal Year 2002; Project Start 30-SEP-1998; Project End 29-FEB-2004 Summary: (Applicant's abstract verbatim): Each year in the USA, more than 500,000 patients are hospitalized with venous thrombosis (VT) and pulmonary embolism (PE). Of these patients, nearly 200,000 die. Despite the magnificent advances in imaging techniques, diagnosis of VT and PE continues to be challenging. Because scintigraphic imaging technique is simple, non-invasive, and permits rapid scanning of the entire body, the FDA has recently approved Tc-99m-AcuTect for imaging clots. AcuTect, however, can neither image old clots nor detect most PE. Fibrin is a major, integral part

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of VT, fresh or old, as well as of PE. During our NIH Phase I study we have developed Tc-99m-fibrin specific peptide, with which in vitro and in vivo imaging results are promising. Our primary goals in the Phase II studies are to evaluate the ability of this agent (Tc-99m/ TP 850) i) to image up to 96 hr old VT and PE, ii) to compare the efficacy of Tc-99m-TP 850 with Tc 99m-AcuTect to image VT and PE, iii) to examine the efficacy of Tc-99m-TP 850 to image fresh and old VT and PE treated in vivo with anticoagulating agent heparin, and iv) to perform pharmacokinetics and radiation dosimetry studies in 10 healthy human volunteers. We believe that the results of these studies will allow us to determine the full potential of Tc-99m-TP 850 and permit us to rapidly initiate clinical trials. PROPOSED COMMERCIAL APPLICATIONS: Following the proposed evaluation in swine and Phase I studies in humans, the agent should be ready to be examined in patients with DVT and PE. Because there are no agents currently available than can scintigraphically provide "hot spot" images of old (24 hr or older) clots and PE, the commercial potential for this agent is very high. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LFM-A13 FOR PREVENTION OF FATAL THROMBOEMBOLISM Principal Investigator & Institution: Mahajan, Sandeep; Paradigm Pharmaceuticals, Llc 2685 Patton Rd St. Paul, Mn 55113 Timing: Fiscal Year 2002; Project Start 15-AUG-2002; Project End 15-FEB-2003 Summary: (provided by applicant): The development of a platelet-rich thrombus on damaged endothelium or atherosclerotic plaques can severely impair the blood flow to vital organs, including the brain, heart, lungs, and kidneys. The contribution of platelets to the pathogenesis of potentially fatal ischemic and/or thromboembolic events, including stroke, myocardial infarct, and pulmonary embolism, is well documented. Therefore, the discovery of effective modulators of platelet function that can prevent thrombus formation is the focus of intensified efforts in translational hematology and cardiovascular biology research.The rationally designed small molecule chemical compound a-cyano-Beta-hydroxy-Beta-methyl-N-(2,5-dibromophenyl)-propenamide (LFM-A13) is a specific inhibitor of the TEC family protein tyrosine kinases, Bruton's tyrosine kinase (BTK) and TEC. Both BTK and TEC play an important role in platelet physiology by regulating the glycoprotein GPVI-FcRy-coupled collagen receptor signaling pathway. We have recently found that LFM-A13 inhibits (a) collagen-induced BTK/TEC stimulation, (b) BTK/TEC-dependent downstream signaling events, (c) biochemical and ultrastructural changes indicative of platelet activation, and (d) collagen-induced platelet aggregation. LFM-A13 was not toxic to mice when administered systemically at dose levels ranging from 1 mg/kg to 100 mg/kg. At nontoxic dose levels, LFM-A13 prolonged the tail bleeding times of mice and improved event-free survival in two mouse models of fatal pulmonary thromboembolism.An oral capsule formulation of LFM-A13 (LFM-A13-F) was developed and showed excellent bioavailability both in mice and dogs. We are now proposing to test the activity of this clinically applicable oral formulation in a mouse model of collagen-induced fatal thromboembolism. After establishing the single agent activity of LFM-A 13-F, we will also examine its antithrombotic effects in combination with the standard antiplatelet agents, dipyndamole or aspirin (alone or in combination). Also examined will be the effect of LFM-A13 alone or in combination with other drugs on the bleeding/clotting times in mice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MANAGEMENT OF PATIENTS WITH SUSPECTED PULMONARY EMBOLISH Principal Investigator & Institution: Rathbun, Suman W.; Medicine; University of Oklahoma Hlth Sciences Ctr Health Sciences Center Oklahoma City, Ok 73126 Timing: Fiscal Year 2002; Project Start 15-FEB-2001; Project End 31-JAN-2006 Summary: The specific aim of this outcomes research project is to obtain the research training and experience necessary to become an independent investigator in clinical research. This training will include both a formal didactic component leading to a Masters of Clinical Epidemiology, and individualized mentoring by the designated sponsor. Training and hands- on experience in research study design, execution, and the responsible conduct Of research win be accomplished by implementing a prospective study to evaluate the effectiveness and safety of a strategy for the management of patients with suspected pulmonary embolism (PE) and non-diagnostic lung scans, which is practical for community hospitals, and which avoids the need for invasive testing with pulmonary angiography in most patients. The hypothesis is that in patients with clinically suspected PE, non-diagnostic lung scans, and adequate cardiorespiratory reserve, clinically important venous thromboembolism (VTE) on follow-up is rare provided that (a) the results of D-dimer and compression ultrasound (C-US) are normal at presentation or (b) if D- dimer is positive, but C-US is normal on serial testing. Those patients with non-diagnostic lung scans, and adequate cardiorespiratory reserve defined by objective, reproducible and previously validated criteria will be eligible and entered into one of three experimental cohorts: VTE negative cohort includes patients with negative C-US and D-dimer results in whom anticoagulant therapy is withheld, Serial testing cohort includes patients with positive D-dimer but negative C-US who are managed by serial C-US testing, and VTE positive cohort includes patients with positive C-US results who are treated with anticoagulant therapy. The primary outcome measure will be the incidence of new symptomatic venous thromboembolism confirmed by objective testing, during a 3 month follow-up period. The analysis will compare the incidences of VTE on follow-up between each of the VTE negative and serial testing cohorts with the VTE positive cohort. If our hypothesis is correct, clinicians will have a safe, practical approach for the management of patients with clinically suspected PE, and non-diagnostic lung scans, which can be easily applied in community hospitals or the outpatient clinic. Completion of this research will be excellent preparation for the submission of an independent Investigator Grant (R-series), and establishment of the investigator as an expert consultant in the area of venous thromboembolic disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MOLECULAR BIOLOGY OF HUMAN COAGULATION FACTOR V Principal Investigator & Institution: Kane, William H.; Associate Professor; Medicine; Duke University Durham, Nc 27706 Timing: Fiscal Year 2002; Project Start 01-JAN-1991; Project End 30-JUN-2005 Summary: (Investigator's abstract) In the United States, cardiovascular disease results in one death every 30 seconds. Clinical disorders such as myocardial infarction, deep vein thrombosis and pulmonary embolism, and stroke are usually precipitated by thrombotic events. Although basic research in thrombosis has lead to significant advances in the diagnosis and treatment of thrombotic disorders current approaches remain sub optimal. Generation of thrombin by the prothrombinase complex plays a particularly important role in the pathogenesis venous thrombosis. The prothrombinase complex consists of the enzyme factor Xa, the cofactor factor Va and a phospholipid

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Pulmonary Embolism

membrane surface. The interaction of factor Xa with the factor Va requires cofactor activation for expression of factor Xa binding sites. The interaction of factor Va with platelet membranes requires expression of phosphatidylserine on the surface of activated platelets or endothelial cells. The binding sites for factor Xa and phospholipid membranes are discontinuous and are located in several different domains. The complexity of these binding sites may allow for the fine regulation of the prothrombinase complex. The molecular bases for these interactions remain poorly understood. The long-term goal of this project is to use integrated molecular, structural and biophysical approaches to understand the interaction of factor Va with biological membranes. During the previous funding period the factor C2 domain was expressed using insect cells and the structures of two crystal forms were elucidated. Expression of factor Va mutants in mammalian cells demonstrated that glycosylation of the C2 domain modulates membrane binding and that two tryptophans located in a mobile solvent exposed loop play a critical role in high affinity binding of factor V to phospholipid membranes containing low concentrations of phosphatidylserine. The specific aims of the present proposal are to further define the binding sites in the factor Va light chain for phospholipid membranes and cellular membranes. Binding sites will be localized using recombinant factor Va mutants, recombinant light chain domains, domain specific and monoclonal antibodies. Experiments will be designed using available crystal structures or molecular models for individual domains. Binding interactions will be characterized using surface plasmon resonance and fluorescence binding assays. This information will provide important new insights into regulation of the prothrombinase complex and may identify sites that could be exploited as novel targets for anti-thrombotic therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OCCUPATIONAL PHYSICAL ACTIVITY AND CIRCULATORY DISEASES Principal Investigator & Institution: Krause, Niklas; Medicine; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2006 Summary: (provided by applicant): Low levels of physical activity have been identified as a major risk factor for cardiovascular disease. However, the evidence for this observation is primarily based on leisure time physical activity. The literature regarding occupational physical activity is controversial. The long-term health effects of different levels of energy expenditure and of different types of activity at work are unknown for most circulatory diseases. However, recent epidemiological research has shown a strong association between prolonged standing at work and hospitalization due to varicose veins, 4-year progression of carotid atherosclerosis, all-cause mortality, and a trend for cardiovascular mortality. The aim of the proposed research is to determine the longterm health effects of different types and levels of occupational physical activity on chronic circulatory diseases. This will be accomplished by an 11-year follow-up of 2682 middle-aged men enrolled in the population-based Kuopio Ischemic Heart Disease Risk Factor Study (KIHD). The KIHD study has the most comprehensive set of biological, behavioral, social, and psychological risk factors of any study, allowing for the control of virtually all known possible confounders. For the first time, the impact of occupational physical activity will be evaluated prospectively on 11-year progression of carotid atherosclerosis and a wide range of specific circulatory diseases, including myocardial infarction, stroke, intermittent claudicating, hypertension, thrombophlebitis, and pulmonary embolism. Specifically, the following questions will be addressed: 1) Is the

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level of daily energy expenditure during work activities associated with circulatory disease and death? 2) Is the ratio of static/dynamic work predictive of morbidity and mortality? 3) Is a predominantly standing working position a risk factor for arteriovascular and venous diseases? 4) Is the impact of occupational physical activity on persons with existing is chemic heart disease or peripheral vascular disease different from the impact on healthy individuals? The long-term goals of this project are to yield useful information for (1) the primary prevention of chronic diseases of the circulatory system, associated disability, and premature death in the aging working population, and (2) the development of evidence-based recommendations for the optimal balance between static and dynamic work, working postures, and overall levels of occupational and leisure time physical activity, for both healthy people and those diagnosed with cardiovascular disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PIOPED II-DATA COORDINATING CENTER Principal Investigator & Institution: Fowler, Sarah E.; Research Professor; Statistics; George Washington University 2121 I St Nw Washington, Dc 20052 Timing: Fiscal Year 2002; Project Start 01-SEP-2000; Project End 31-JUL-2004 Summary: This is a multi-center collaborative study to determine the sensitivity, specificity, positive predictive value, and negative predictive value of contrast enhanced spiral computed tomography (spiral CT) for the diagnosis of acute pulmonary embolism (PE). Pulmonary embolism is common, yet frequently undiagnosed and fatal. Ventilation/perfusion scan is the most frequently used test, but is non-diagnostic in 72 percent of patients with suspected PE, and in 57 percent of patients with proven PE. Pulmonary angiography is the currently definitive diagnostic test, but there is hesitancy to use it because of morbidity,' discomfort, cost, and lack of availability in community hospitals. Contrast enhanced spiral CT is a nearly noninvasive test that offers the possibility of a definitive diagnosis of PE by showing the outline of the thrombus in a pulmonary artery. However, its utility in the diagnosis of PE is unknown. Even though spiral CT has not been adequately validated, many physicians now use it as a definitive and only diagnostic test for PE, or as a definitive test in patients in whom the ventilation/perfusion lung scan is non-diagnostic. This could lead to over treatment or under treatment, and potential serious complications. The role of spiral CT in the diagnosis of PE requires the accurate evaluation that will be made in this investigation. In response to reviewer suggestions on the original application, this revised application proposes to use a composite reference standard based on ventilation / perfusion lung scan, compression ultrasound of the lower extremities, and angiography. The strengths of the proposal are: 1) the importance of the problem of PE in terms of lives lost from under diagnosis, and major bleeding from over diagnosis; 2) the potential applicability of a new technology for the diagnosis of PE that will have widespread availability; and 3) the investigator team. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PLASMINOGEN ACTIVATION & SK: STRUCTURE-FUNCTION Principal Investigator & Institution: Reed, Guy L.; Associate Professor; Medicine; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 01-JUL-1998; Project End 30-JUN-2006 Summary: (provided by applicant): The plasminogen (Pg) system dissolves the thrombi (blood clots) that cause heart attacks and strokes. The Pg system is tightly regulated by

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Pulmonary Embolism

protein-protein interactions with inhibitors, activators, substrates, etc. The cleavage of Pg to plasmin by streptokinase (SK), and other Pg activators, initiates fibrinolysis (clot dissolution) which saves the lives of heart attack patients. Recent studies have suggested that mechanistic insights into the regulation of the Pg system could further reduce the mortality from heart attacks, and improve the treatment of strokes, pulmonary embolism, etc. Because of its physiologic and therapeutic importance, our long term goal is to help elucidate the protein-protein interactions that regulate and modify the activity of the Pg system. The interactions between Pg and the indirect Pg activator SK are among the most biologically and medically important of these contacts. Studies performed in the first phase of this grant have helped to delineate the elegant interactions through which SK converts Pg (without cleavage) into the most catalytically efficient Pg activator, Insights have been made into defining the mechanisms through which: 1) SK forms a tight stable 'activator complex' with Pg (or plasmin), 2) SK nonproteolytically generates the latent active site in Pg creating a 'virgin enzyme' (Pg*), and 3) SK modifies the substrate specificity of Pg* or plasmin so that the complex can cleave Pg molecules. This continuation proposal is directed towards further dissecting the process of indirect Pg activation, in order to determine the novel mechanisms by which SK becomes a fibrin-dependent (or t-PA-like enzyme), to define whether fibrindependent SKs have the potential to be superior fibrinolytic agents, to understand the role of the Pg kringle domains in indirect Pg activation and, to define the intermolecular interactions that occur in the SK-Pg complex which are required for a SK-type of mechanism. In a broad scientific sense, insights into this unique process of indirect Pg activation should enlarge our understanding of how the catalytic activity and specificity of Pg system is regulated, and could suggest rational ways to alter the indirect Pg activators so as to improve their therapeutic value for patients with thrombosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROSPECTIVE INVESTIGATION OF PE DX-II Principal Investigator & Institution: Leeper, Kenneth V.; Associate Professor of Medicine; Medicine; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2002; Project Start 01-SEP-2000; Project End 31-JUL-2004 Summary: This is a multi-center collaborative study to determine the sensitivity, specificity, positive and negative predictive value of contrast enhanced spiral-computed tomography (spiral CT) scan for the diagnosis of acute pulmonary embolism (PE). PE is common, yet frequently undiagnosed and fatal. Ventilation/perfusion lung scans, the usual initial test are non- diagnostic in 72 percent of patients with suspected PE, and 57 percent of patients with subsequently proven PE. Pulmonary angiography is the definitive diagnostic test, but there is associated with morbidity, discomfort, cost, and lack of availability in community hospitals. Noninvasive leg tests, particularly venous ultrasonography, permit a strategy of management by identifying deep venous venous thrombosis (DVT) and potentially obviating the need for pulmonary angiography. Spiral CT is nearly a noninvasive test that offers the possibility of a definitive diagnosis of PE by showing the outline of the thrombus in a pulmonary artery. However, its utility in the diagnosis of PE is unknown. Even though spiral CT has not been adequately validated, its use is becoming widespread as a definitive diagnostic test for PE, or diagnostic arbiter for non-diagnostic lung scans in many hospitals. This cold lead to over treatment and under treatment, both of which have serious potential complications. This investigation will accurately evaluate the role of spiral CT scan in the diagnosis of PE by comparison with pulmonary angiography, V/Q lung scan in patients without prior PE, pulmonary angiography, or compression ultrasound of the

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lower extremities in patients with no prior deep venous thrombosis. PE will be diagnosed based on a high probability lung scan in patients with no prior PE, pulmonary angiography, or compression ultrasound of the lower extremities in patients with no prior DVT. DVT detected by venous ultrasound will serve as a surrogate for the diagnosis of PE. Pulmonary embolism will be excluded by pulmonary angiography or nearly normal lung scans with no adverse outcome (i.e. PE or DVT) on follow-up treated patients. Among patients with a low probability lung scan, PE will be excluded by 2 negative venous compression ultrasound studies at 1 week intervals followed by 6 months of follow-up with no treatment and no recurrent PE or DVT. The strengths of this proposal are: 1) the importance of the problem of PE in terms of lives lost from under-diagnosis, and major bleeding from over-diagnosis 2) potential applicability of a new technology for the diagnosis of PE that will have widespread availability, 3) protocol parallels standard diagnostic strategy without subjecting the patients to risk entirely for the acquisition of data. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROSPECTIVE INVESTIGATION OF PULMONARY EMBOLISM DX II Principal Investigator & Institution: Hales, Charles A.; Professor of Medicine; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 01-SEP-2000; Project End 31-JUL-2004 Summary: This is a multicenter collaborative study to determine the sensitivity, specificity, positive predictive value, and negative predictive value of contrast enhanced spiral computed tomography (spiral CT) for the diagnosis of acute pulmonary embolism (PE). Pulmonary embolism is common, yet frequently undiagnosed and fatal. Ventilation/perfusion lung scans are the most commonly used test. However, they are nondiagnostic in 72 percent of patients with suspected PE, and in 57 percent of patients with proven PE. Pulmonary angiography is the currently definitive diagnostic test, but there is hesitancy to use it because of morbidity, discomfort, cost, and lack of availability in community hospitals. Contrast enhance spiral CT is a nearly noninvasive test that offers the possibility of a definitive diagnosis of PE by showing the outline of the thrombus in a pulmonary artery. However, its utility in the diagnosis of PE is unknown. Even though spiral CT has not been adequately validated, physicians at many hospitals now use it as a definitive and only diagnostic test for PE, or as a definitive test in patients in whom the ventilation/perfusion lung scan is nondiagnostic. This could lead to overtreatment or undertreatment, both of which have serious potential complications. The role of spiral CT in the diagnosis of PE requires an accurate evaluation which will be made in this investigation by comparison with pulmonary angiography. The strengths of this proposal are: 1) the importance of the problem of PE in terms of lives lost from underdiagnosis, and major bleeding from overdiagnosis 2) the potential applicability of a new technology for the diagnosis of PE that will have widespread availability and 3) the investigator team. Noninvasive leg tests, particularly venous ultrasonography, permit a strategy of management by treatment on the basis of venous thromboembolic disease (PE or deep venous thrombosis), ventilation/perfusion lung scan, or compression ultrasound of the lower extremities. Pulmonary embolism will be diagnosed on the basis of a high probability ventilation/perfusion lung scan in patients with no prior PE, pulmonary angiography, or compression ultrasound of the lower extremities in patients with no prior deep venous thrombosis. Deep venous thrombosis detected by venous ultrasound will serve as a surrogate for the diagnosis of PE. Pulmonary embolism will be excluded by pulmonary angiography, or a nearly

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normal or normal ventilation/perfusion lung scna with no adverse outcome (i.e. PE or DVT) on follow-up of untreated patients. Among patients with a low probability ventilation/perfusion lung scan, PE will be excluded by 2 negative venous compression ultrasound studies at 1 week intervals followed by 6 months of follow-up with no treatment and at 1 week intervals, followed by 6 months of follow-up with no treatment and no recurrent PE or DVT. The protocol parallels standard diagnostic strategy, without subjecting the patients to risk entirely for the acquisition of data. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROSPECTIVE INVESTIGATION OF PULMONARY EMBOLISM DXII Principal Investigator & Institution: Sostman, Henry D.; Chairman; Radiology; Weill Medical College of Cornell Univ New York, Ny 10021 Timing: Fiscal Year 2003; Project Start 01-SEP-2000; Project End 31-JUL-2004 Summary: This is a multicenter collaborative study to determine the sensitivity, specificity and predictive values of contrast enhanced spiral computed tomography (spiral CT) for the diagnosis of acute pulmonary embolism (PE). Pulmonary embolism is common, yet frequently undiagnosed and fatal. Ventilation/ perfusion lung scans are the most commonly used test. However, they are nondiagnostic in 72 percent of patients with suspected PE and in 57 percent of patients with subsequently proven PE. Pulmonary angiography is the definitive diagnostic test in such patients, but there is hesitancy to use it because of morbidity, discomfort, cost, and lack of availability is community hospitals. Noninvasive leg tests, particularly venous ultrasound, permit a strategy of management by treatment on the basis of venous thromboembolic disease (PE or DVT). Spiral CT is a nearly noninvasive test that offers the possibility of a definitive diagnosis of PE by showing the outline of the thrombus in a pulmonary artery. However, its utility in the diagnosis of PE is not established. Even though spiral CT has not been adequately validated, many hospitals now use it as a first diagnostic test for PE, or as a definitive test in patients in whom the ventilation/perfusion lung scan is nondiagnostic. This could lead to over- or undertreatment, which have serious potential complications. In view of the potential applicability of spiral CT, this investigation is proposed to test its sensitivity, specificity, positive and negative predictive values, using contemporary diagnostic reference standard methods. The strengths of this proposal are: 1) the importance of the problem of PE diagnosis, 2) the potential of a widely available technology for the diagnosis, 3) a protocol that parallels standard diagnostic strategy without subjecting patients to risk only for data acquisition, 4) a strong team of investigators, which has collaborated previously in successful research in PE. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PROSPECTIVE INVESTIGATION OF PULMONARY EMBOLISM DXII Principal Investigator & Institution: Woodard, Pamela K.; Radiology; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 01-SEP-2000; Project End 31-JUL-2004 Summary: (Adapted from the applicant's abstract) This is a multicenter collaborative study to determine the sensitivity, specificity, positive and negative predictive value of contrast enhanced spiral computed tomography (spiral CT) for the diagnosis of acute pulmonary embolism (PE). Pulmonary embolism is common, yet frequently

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undiagnosed and fatal. Spiral CT is a nearly noninvasive test that offers the possibility of a definitive diagnosis of PE by showing the outline of the thrombus in a pulmonary artery. However, its utility in the diagnosis of PE is unknown. Even though spiral CT has not been adequately validated, physicians at many hospitals now use it as a definitive and only diagnostic test. This could lead to overtreatment or undertreatment, both of which have serious potential complications. The role of spiral CT in the diagnosis of PE requires an accurate evaluation which will be made in this investigation by a composite of diagnostic tests including pulmonary angiography, ventilation/perfusion lung scans, venous compression ultrasound, and outcome analysis. The strengths of this proposal are: 1) the importance of the problem of PE in terms of lives lost from underdiagnosis and major bleeding from overdiagnosis; 2) the potential applicability of a new technology for the diagnosis of PE that will have widespread availability; 3) the protocol parallels standard diagnostic strategy without subjecting the patients to risk entirely for the acquisition of data and 4) the team of investigators is strong and has collaborated previously in successful research in PE. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROSPECTIVE INVESTIGATION OF PULMONARY EMBOLISM DXII Principal Investigator & Institution: Popovich, John; Medicine; Case Western Reserve Univ-Henry Ford Hsc Research Administraion Cfp-046 Detroit, Mi 48202 Timing: Fiscal Year 2002; Project Start 01-SEP-2000; Project End 31-JUL-2004 Summary: This application is part of a multicenter clinical trial titled the Prospective Investigation of Pulmonary Embolism Diagnosis-II (PIOPED-II). Pulmonary embolism (PE) is common, yet frequently undiagnosed. Pulmonary angiography is the definite diagnostic test in such patients, but there is hesitancy to use it because of morbidity, discomfort, cost and lack of availability in community hospitals. Serial noninvasive leg doppler examinations reduce the need for pulmonary angiography, and many physicians, incorporate their use in diagnostic algorithms. Irrespective, large numbers of patients would require pulmonary angiography. Contrast enhanced spiral computed tomography (CT) is minimally invasive test that offers the possibility of a definite diagnosis of PE by showing the outline of the thrombus in a pulmonary artery. It requires only an intravenous injection of contrast material, and, therefore, is safe for most patients. Several small investigations have shown marked differences in the sensitivity of spiral CT for the detection of acute PE. In view of the potential applicability of spiral CT, this investigation is proposed to study its role in the diagnosis of venous thromboembolic disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PROSPECTIVE INVESTIGATION OF PUMONARY EMBOLISM DX II Principal Investigator & Institution: Hull, Russell D.; University of Calgary 2500 University Dr Nw Calgary, Timing: Fiscal Year 2002; Project Start 01-SEP-2000; Project End 31-JUL-2004 Summary: A multi-center collaborative study to determine the sensitivity, specificity, positive predictive value and negative predictive value of contrast enhanced spiral computed tomography (spiral CT) for diagnosis of acute pulmonary embolism (PE). Pulmonary embolism is common, yet frequently undiagnosed and fatal. Ventilation/perfusion lung scans are the most commonly used test. However, they are non-diagnostic in 72% of patients with suspected PE and in 57% of patients with proven

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PE. Currently, Pulmonary Angiography is the definitive diagnostic test, but, there is hesitancy to use it because of morbidity, discomfort, discomfort, cost and lack of availability in community hospitals. Contrast enhanced spiral CT is a nearly noninvasive test that offers the possibility of a definitive diagnosis of PE by showing the outline of the thrombus in a pulmonary artery. However, its utility in the diagnosis of PE is unknown. Although spatial CT has not been adequately validated, physicians at many hospitals now use it as a definitive and only diagnostic test for PE, or as a definitive test in patients in whom the ventilation/perfusion lung scan is nondiagnostic. This could lead to over-treatment or under- treatment, of which, both have potential for serious complications. The role of spiral CT in the diagnosis of PE requires an accurate angiography. The strengths of this proposal are: 1) the importance of the problem of PE in terms of lives lost from under-diagnosis 2) the potential applicability of a new technology for the diagnosis of PE that will have widespread availability 3) the investigation team. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: P-SELECTIN PATHOGENESIS

IS

CENTRAL

TO

VENOUS

THROMBOSIS

Principal Investigator & Institution: Wakefield, Thomas W.; Surgery; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2006 Summary: Venous thrombosis (VT) is a national health concern, occurring at a constant rate over the past 20 years, with an annual incidence of at least 250,000 cases. It is estimated that deep venous thrombosis and pulmonary embolism are associated with approximately 300,000 to 600,000 hospitalizations and as many as 50,000 deaths per year. Chronic venous insufficiency, the sequela of venous thrombosis, affects approximately 400,000 to 500,000 patients with skin ulceration, 6 to 7 million patients with skin stasis changes, and up to 28 percent of patients with significant iliofemoral DVT over time will develop severe edema and skin changes which may lead to venous ulceration. VT in short costs the health system billions of dollars. Selectins are mucin like glycoprotein cell adhesion molecules that are expressed by activated endothelial cells and platelets and mediate leukocyte-platelet, leukocyte-endothelial cell, and leukocyteleukocyte interactions. Preliminary data suggest that P-selectin is temporally related to the initiation and maintenance of the inflammatory and thrombotic response associated with VT. Our research hypotheses include: P-selectin is casually related to VT inflammation and thrombosis amplification; inhibition of P-selectin alone or augmented with other agents will decrease inflammation and thrombosis without systemic anticoagulant complications; and P-selectin inhibition will stimulate thrombolysis of thrombus that does form, augmenting other fibrinolytic agents. We will address these hypotheses with three specific aims: Specific Aim 1: To determine if the mechanism of inflammation associated with venous thrombosis involves P-selectin. This will be investigated using genetically altered mice which express high levels of circulating soluble P-selectin, and the effect of blocking the excess soluble P-selectin. They will then be contrasted to wild type mice administered soluble P-selectin, and mice genetically lacking P- selectin. Specific Aim 2: To assess P-selectin inhibition and to test the efficacy of other antithrombotic agents for VT treatment, agents with different mechanisms of action including inhibition of factor Xa and direct thrombin inhibition. Additionally, to combine agents to determine which agent or agents offer the best treatment for VT without anticoagulant activity. Specific Aim 3: To determine if direct P-selectin inhibition augments both spontaneous and pharmacologically induced thrombolysis

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and specifically to determine if P-selectin inhibition impairs fibrin deposition or increases fibrinolysis. These studies will define the role of P-selectin in VT pathogenesis, treatment and thrombolysis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REACTION AND TRANSPORT DYNAMICS IN HUMAN BLOOD Principal Investigator & Institution: Diamond, Scott L.; Associate Professor; Chemical Engineering; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 15-JUL-1996; Project End 31-MAR-2005 Summary: (Verbatim from Applicant's Abstract): In the context of a given genotype and phenotype, the dynamics of blood clot assembly ultimately dictate: thrombosis; thrombolytic susceptibility of clots; stroke during cardiopulmonary bypass; restenosis after angioplasty; wound healing/inflammation; and pathogenesis of deep vein thrombosis or pulmonary embolism. During blood coagulation, activated platelets and neutrophils from homotypic and heterotypic aggregates through over ten receptormediated pathways while triggering thrombin formation and fibrin polymerization. Yet less is known quantitatively about the strengths and kinetics of platelet-platelet and platelet-neutrophil bonding that leads to aggregation or deposition under coagulating whole blood flow conditions or the biochemical reactivity of these aggregates. Furthermore, temporal resolution of events lasting only a few milliseconds is rarely achieved in most experiments. In vitro high speed imaging experiments will utilize human blood cells and proteins for kinetic studies of these interactions under controlled hemodynamic and coagulation conditions. Probability distributions and kinetic data from these experiments will be used to gain improved mechanistic understanding of human blood phenomena from receptor dynamics to vessel occlusion, in the hemodynamic setting. By defining the molecular dynamics of how blood clots are assembled under flow conditions as well as defining the flow regulation of various clotting scenarios, the risks of unregulated clotting, bleeding, and embolism will be more quantitatively understood for a given disease progression. Specific aims are: Aim 1 High speed imaging of platelet bonding dynamics that regulate thrombosis in clotting blood with emphasis on bond life dynamics. Aim 2 High speed imaging of neutrophil bonding dynamics that enhance cellular deposition with emphasis on selectin mediated pathways, erythrocyte interactions and membrane tethering. Aim 3 Quantifying mechanisms by which neutrophils act as procoagulant participants during clot assembly under defined flow conditions. Aim 4 Develop a set of generalized computational tools for the study of heterotypically aggregating-reacting blood. Overall, these studies seek to provide fundamental insight into cell-cell interactions and coagulation biochemistry that occur under flow. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: OVERLOAD

RIGHT

VENTRICULAR

DYSFUNCTION

AFTER

PRESSURE

Principal Investigator & Institution: Greyson, Clifford R.; Medicine; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2007 Summary: (provided by applicant): Right ventricular (RV) contractile failure from acute RV pressure overload is an important cause of morbidity and mortality in conditions such as massive pulmonary embolism, hypoxic pulmonary vasoconstriction, and following cardiopulmonary bypass and cardiac transplantation. The applicant

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Pulmonary Embolism

previously demonstrated that intrinsic RV contractile function is depressed following a brief period of pressure overload, even after restoration of normal loading conditions. The overall purpose of the proposed research is to determine the mechanism of impaired RV contractile function following acute RV pressure overload. RV dysfunction following pressure overload is qualitatively similar to left ventricular stunning after ischemia-reperfusion, and to skeletal muscle dysfunction after strenuous exercise; these have been hypothesized to result from proteolysis of myofibrillar or cytoskeletal proteins by the calcium-sensitive cysteine protease calpain, or from degradation of the extracellular collagen matrix. Therefore, we plan to test the following hypotheses: #1. RV dysfunction from acute RV pressure overload is associated with and temporally related to proteolytic degradation of myofibrillar proteins, cytoskeletal proteins, and/or the extracellular collagen matrix (ECM). #2. Such proteolytic degradation is manifested by alterations in myofibrillar ATPase activity, disruption of myocardial sarcomere architecture, and or morphologic alterations in the extracellular collagen weave. #3. Degradation of myofibrillar proteins, cytoskeletal proteins, and or the ECM is caused by stress-related activation of calpain and/or of matrix metalloproteinases (MMPs). We plan to determine whether calpain and/or MMPs are activated during acute RV pressure overload, and whether RV dysfunction following acute RV pressure overload can be prevented by specific inhibitors of calpain or MMPs; use 1D and 2D polyacrylamide gel electrophoresis (PAGE), Western blotting and mass spectrometry/peptide fingerprinting to determine the time course of degradation and/or phosphorylation of major myofibrillar and cytoskeletal proteins during acute RV pressure overload; measure changes in RV myofibrillar ATPase activity; and assess myocardial ultrastructure following acute pressure overload. Even if the hypothesized mechanism is not confirmed, the methods employed (so-called proteomics) are likely to identify other potential mechanisms of RV contractile dysfunction, and will contribute to the development of a more complete 2D-PAGE map of porcine myocardial proteins. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SURROGATE MARKERS FOR SEVERE PULMONARY EMBOLISM Principal Investigator & Institution: Kline, Jeffrey A.; Carolinas Medical Center Box 32861 Charlotte, Nc 28203 Timing: Fiscal Year 2003; Project Start 08-JUL-2003; Project End 30-JUN-2006 Summary: (provided by applicant): Echocardiography can help risk-stratify the severity of pulmonary embolism (PE) diagnosed in normotensive patients. However, because echocardiography is not uniformly available in U.S. hospitals, more accessible surrogate criteria are needed: to facilitate the immediate recognition of disabling PE in hemodynamically stable patients. Prior work by the Pi has led to the hypothesis that cardiopulmonary stress from severe PE can be recognized by abnormalities in vital signs, the 12- lead ECG and the serum troponin measurement. For this project, a screening instrument to rule out severe PE has been defined asthe combination of a shock index (pulse/systolic blood pressure) 91 percent, a Daniel ECG score <8 points, and a troponin I <0.4 ng/mh The hypothesis of this project is that patients with a negative screening instrument will not have right ventricular (RV) strain on echocardiography and are at very low risk of death or cardiopulmonary disability from PE treated with standard: anticoagulation. The first specific aim of the project is to test the diagnostic accuracy of the proposed screening instrument, using RV strain on transthoracic echocardiography as the criterion standard. The second aim will compare the diagnostic accuracy of the screening instrument with echocardiography for the prediction of an adverse outcome from PE. Because the screening instrument may

Studies

21

notpredict RV damage from recurrent or unresolved PE, the second hypothesis is that nonmalignant thrombophilic conditions will increase risk of an adverse outcomefrom PE. Accordingly, :the third aim will test if patients with PE complicated by an adverse outcome are more likely to have antiphospholipid antibodies, or factor V Leiden G1691A, prothrombin G20210A, methylenetetrahydrofolate reductase C677T mutations, or low red blood cell methylfolate or high :plasma homocysteine concentrations, compared with patients with PE and no adverse outcome. An adverse clinical outcome will include death or anoxic brain insult :within 30 :days of diagnosis, recurrent PE, or cardiopuimonary disability, determined six months after diagnosis. Cardiopulmonary disability will be defined by New York Heart Association functional class II or worse, a repeat transthoracic echocardiogram with persistent RV strain, and a six-minute walk distance less than 330 meters. This study will determine if criteria that are widely and immediately available in most hospitals can be used to risk-stratify severity of PE and to clarify the role of nonmalignant thrombophilias on the prognosis of PE. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TAMOXIFEN--RISK THROMBOEMBOLISM

OF

MI,

STROKE

AND

VENOUS

Principal Investigator & Institution: Bernstein, Leslie; Professor; Preventive Medicine; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2001; Project Start 15-SEP-1997; Project End 30-JUN-2004 Summary: (Adapted from Investigator's Abstract) Tamoxifen, a synthetic, non-steroidal antiestrogen in breast tissue, has been successfully used to treat breast cancer and is now being evaluated as a breast cancer chemopreventive agent. Tamoxifen produces some estrogen-like effects. It has a favorable impact on lipid profiles, but whether it reduces risk of coronary heart disease and stroke or increases risk of venous thromboembolic events (VTE: deep venous thrombophlebitis and pulmonary embolism) is uncertain. In the U.S., the Breast Cancer Prevention Trial was designed to address heart disease and stroke prevention, but recruitment has been suboptimal due to lower than expected subject accrual especially among older women. Thus, the trial lacks statistical power to pursue these issues. As tamoxifen is already widely used in the treatment of breast cancer and may become widely used in disease-free women, the investigators note that it is important to assess its potential risks and benefits. The overall objectives of this HMO-based case-control study are as follow: 1) to determine whether tamoxifen treatment for breast cancer reduces the risk of incident myocardial infarction (MI) and stroke and increases the risk of incident VTE; 2) to determine whether any tamoxifen effects are restricted to current users and to quantify any dose, duration or latency effects; and 3) to determine whether any observed effects of tamoxifen on risk of these events are explained by or modified by relevant disease risk factors. Cases will be breast cancer patients diagnosed at a Los Angeles County Kaiser Permanente Southern California (KPSC) health care centers who subsequently are diagnosed with incident MI, stroke or VTE. Cases will be identified by linking data from the population-based cancer registry for Los Angeles County to the KPSC discharge database. Two controls will be individually matched to each case. Controls will be KPSC members diagnosed with breast cancer who have not had the case-defining event, who matched the cases on year of diagnosis and year of birth within 3 years. Neither cases nor controls can have had other cancer diagnoses except a second primary breast cancer. Controls must be alive at the time their matched case experienced her case-defining event. Breast cancer treatment and relevant risk factor data will be collected and analyzed for 160 breast cancer patients diagnosed with MI and 320 controls, for 260 breast cancer patients diagnosed with

22

Pulmonary Embolism

stroke and 520 controls, and 210 breast cancer patients diagnosed with VTE and 420 controls. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THROMBOSIS TARGETED MRI CONTRAST AGENT Principal Investigator & Institution: Danilich, Michael J.; Luna Innovations, Inc. 2851 Commerce St Blacksburg, Va 24060 Timing: Fiscal Year 2003; Project Start 22-AUG-2003; Project End 31-JUL-2004 Summary: (provided by applicant): This proposal addresses the need for a minimally invasive diagnostic assay for the evaluation of pathological blood clots in patients suspected of developing intravascular blood clots that may manifest themselves as pulmonary embolism (PE), deep vein thrombosis (DVT) or thrombotic stroke. Indeed, thrombosis (the formation of blood clots) remains the leading cause of morbidity and mortality in the United States. Luna Innovations proposes to develop a trimetasphere based magnetic resonance imaging contrast agent for site directed thrombosis imaging. Luna Innovations will manufacture an appropriate trimetasphere nanomaterial (such as like Gd2ScN@C80) and functionalize it in preparation for conjugation to a monoclonal antibody with the highest specificity to a neo-epitope on the blood clot. Following this the trimetasphere-antibody complex will be evaluated in vitro experiments for the capability of the complex to target, image and destroy the blood clot. In phase I, Luna will demonstrate the ability of this complex to perform this task and optimize the complex for in vivo diagnostic imaging for phase II Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: THROMBUS RESOLUTION IS CXC CHEMOKINE DEPENDENT Principal Investigator & Institution: Henke, Peter K.; Surgery; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 30-JUN-2007 Summary: (provided by applicant): Long term objectives: The proposed studies, coupled with closely mentored laboratory guidance, seminars and course work will significantly broaden the applicant's scientific education and lead to an independent investigator status. Research: Unlike much arterial vascular disease, venous thrombotic disease lacks a consistently effective therapeutic approach outside of anticoagulation prophylaxis and treatment. Deep venous thrombosis resolution involves inflammatory mediator and cellular responses similar to the wound healing process. Chemokines are central to many inflammatory processes. The CXC subfamily are primary chemoattractants and activators of PMNs, and are directly proangiogenic. This proposal will utilize cell culture and two small animal models of DVT to answer the following specific aims: 1) To define the role of CXC chemokines and their effector leukocytes on molecular and cellular deep vein thrombosis resolution, 2) To determine the in vitro role of CXC chemokines on neutrophil derived fibrincilytic and angiogenic mediators, and 3) To determine the role of neutrophils and the effect of exogenous proangiogenic and angiostatic CXC chemokines on physiological deep vein thrombosis resolution. Molecular biological, immunological, as well as in vitro and in vivo angiogenesis bioassays, in conjunction with physiologic assays, will be used to achieve the above aims. Defining the basic chemokine mediated DVT resolution pathophysiology will potentially yield phamacologic or cellular based therapies to hasten DVT resolution for decreased peri-thrombotic inflammation, decreased vein wall damage, and decreased risk of pulmonary embolism.

Studies

23

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

Project Title: VENOUS THROMBOEMBOLISM AMONG CALIFORNIA CANCER PATIENTS Principal Investigator & Institution: Chew, Helen K.; Internal Medicine; University of California Davis Sponsored Programs, 118 Everson Hall Davis, Ca 95616 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): Venous thromboembolism (VTE, includes both venous thrombosis and pulmonary embolism) is a frequent complication among patients with cancer. However, there is surprisingly little data regarding the incidence and time course of VTE and the risk of recurrent VTE among patients with a specific malignancy defined by histologic type and stage. In addition, it is not clear to what degree age, sex, ethnicity, stage, histologic type, and treatment predict the development of VTE. This information is important because there is preliminary data suggesting that use of anticoagulants, such as warfarin or low molecular weight heparin, may be beneficial in the primary prevention of VTE among cancer patients. The specific aims of this application are: 1) to define a cohort of patients diagnosed with one of the ten most frequent cancers in California and to identify hospital-reported cases of VTE in this cohort by linking the California Cancer Registry with the California Patient Discharge Data Set; 2) to determine and compare the incidence and time course of incident VTE after diagnosis of the most frequent cancers in California; 3) to determine demographic, treatment- and disease-related risk factors associated with developing VTE after diagnosis of the most frequent cancers in California; 4) to determine predictors of death within two years of diagnosis of each of the ten most frequent cancers in California; and 5) to determine the incidence of recurrent VTE and re-hospitalization for bleeding within a six-month period after diagnosis of incident VTE and to compare this to the incidence in age- and sex-matched patients with VTE who do not have cancer. The hypothesis are: 1) a cohort of cancer patients who develop VTE can be identified through the California Cancer Registry and the California Patient Discharge Data Set; 2) there is a significant variation in the incidence and time course of incident VTE among the ten most frequent cancer diagnoses, and among the different stages of each of these malignancies; 3) for each type of cancer, there is ethnic variation in the incidence of VTE, and factors such as age, stage, and therapy, will influence the observed rates of VTE in cancer patients; 4) for all malignancies, the development of VTE within 2 years of diagnosis is an independent predictor of death within 2 years of diagnosis; and 5) patients with cancer who develop VTE have a higher incidence of both recurrent VTE and severe bleeding complications related to anticoagulation therapy compared to ageand sex-matched patients with VTE who do not have cancer. We propose to take advantage of our ability to merge the extensive and mature California Cancer Registry with the linked California Patient Discharge Data Set in order to examine these questions. Results of this research will provide important data regarding the natural history of VTE in cancer patients and serve as the basis for designing prospective studies aimed at primary prevention of VTE in high-risk groups. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Pulmonary Embolism

E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “pulmonary embolism” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for pulmonary embolism in the PubMed Central database: •

Cardiac troponin T in the severity assessment of patients with pulmonary embolism: cohort study. by Janata K, Holzer M, Laggner AN, Mullner M.; 2003 Feb 8; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=143527

•

Diagnosis of fulminant pulmonary embolism by transthoracic echocardiography. by Tovar EA, Borsari A, Kunelis CT, Song M.; 1997; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=325400

•

Diagnosis of pulmonary embolism. by Kearon C.; 2003 Jan 21; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=140429

•

Diagnostic value of gas exchange tests in patients with clinical suspicion of pulmonary embolism. by Prediletto R, Miniati M, Tonelli L, Formichi B, Di Ricco G, Marini C, Bauleo C, Allescia G, Cocci F, Monti S, Pistolesi M, Giuntini C.; 1999; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=29023

•

Emergent Surgery for Massive Pulmonary Embolism on the Basis of Clinical Diagnosis. by Brevetti GR, O'Brien B, Coomer CL, Hall TS, Brevetti LS, Jablons DM.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=161905

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Excluding pulmonary embolism with helical (spiral) computed tomography: Evidence is catching up with enthusiasm. by Kearon C.; 2003 May 27; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=155960

•

Indications for Thrombolytic Therapy in Acute Pulmonary Embolism. by Dieck JA, Ferguson JJ III.; 1989; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=324838

•

Initial Clinical Experience with an Endoluminal Spiral Prosthesis for Treating Complicated Venous Thrombosis and Preventing Pulmonary Embolism. by Jakob H, Oelert H, Schmiedt W, Teusch P, Iversen S, Hake U, Schild H, Maass D.; 1989; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=324856

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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25

•

Massive pulmonary embolism 3 hours after cardiopulmonary bypass. An exceeding rare case. by Masiello P, Mastrogiovanni G, Iesu S, Panza A, Triumbari F, Di Benedetto G.; 1994; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=325196

•

Protected Iliofemoral Venous Thrombectomy in a Pregnant Woman with Pulmonary Embolism and Ischemic Venous Thrombosis. by Neri E, Civeli L, Benvenuti A, Toscano T, Miraldi F, Capannini G, Muzzi L, Sassi C.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=116741

•

Pulmonary Embolism after Pacemaker Implantation. by Martinez-Selles M, Bueno H, Almendral J, Diaz-Castro O.; 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101212

•

Pulmonary embolism due to compression of the inferior vena cava by a hepatic hemangioma. by Paolillo V, Sicuro M, Nejrotti A, Rizzetto M, Casaccia M.; 1993; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=325057

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Pulmonary embolism possibly associated with olanzapine treatment. by Waage IM, Gedde-Dahl A.; 2003 Dec 13; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=292991

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Pulmonary embolism. by Mathew TC, Ramsaran EK, Benotti JR.; 1995; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=325290

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Seasonal variations in hospital admission for deep vein thrombosis and pulmonary embolism: analysis of discharge data. by Boulay F, Berthier F, Schoukroun G, Raybaut C, Gendreike Y, Blaive B.; 2001 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=55575

•

The relationship between FV Leiden and pulmonary embolism. by Hooper WC, De Staercke C.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=64819

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 pulmonary embolism, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “pulmonary 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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Pulmonary Embolism

embolism” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for pulmonary embolism (hyperlinks lead to article summaries): •

A comparison of spiral computed tomography and latex agglutination D-dimer assay in acute pulmonary embolism using pulmonary arteriography as gold standard. Author(s): Nilsson T, Soderberg M, Lundqvist G, Cederlund K, Larsen F, Rasmussen E, Svane B, Brohult J, Johnsson H. Source: Scandinavian Cardiovascular Journal : Scj. 2002 December; 36(6): 373-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12626206

•

A cost-effective objective approach to aid diagnosis of deep-vein thrombosis (DVT) and pulmonary embolism (PE). Author(s): Sinharay R. Source: Qjm : Monthly Journal of the Association of Physicians. 2003 September; 96(9): 687-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12925724

•

A lethal pulmonary embolism during percutaneous vertebroplasty. Author(s): Chen HL, Wong CS, Ho ST, Chang FL, Hsu CH, Wu CT. Source: Anesthesia and Analgesia. 2002 October; 95(4): 1060-2, Table of Contents. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12351294

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A pulmonary embolism case presenting with upper abdominal and flank pain. Author(s): Unluer EE, Denizbasi A. Source: European Journal of Emergency Medicine : Official Journal of the European Society for Emergency Medicine. 2003 June; 10(2): 135-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12789072

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A pulmonary embolism treated with the Angiojet technique in a patient with double outlet right ventricle. Author(s): Brenes JC, Ferreira A, Galindo A. Source: J Invasive Cardiol. 2004 January; 16(1): 42-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14699224

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A rebuttal: withholding anticoagulation in patients with suspected pulmonary embolism and a low probability ventilation perfusion scan: an unacceptable risk. Author(s): Perrier A, Bounameaux H. Source: Thrombosis and Haemostasis. 2002 October; 88(4): 702. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12362255

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A structured clinical model for predicting the probability of pulmonary embolism. Author(s): Miniati M, Monti S, Bottai M. Source: The American Journal of Medicine. 2003 February 15; 114(3): 173-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12637130

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Abnormalities on cardiopulmonary exercise test in a dyspneic patient. A case report of unsuspected pulmonary embolism. Author(s): Bhagat R, Schreiber G. Source: Respiration; International Review of Thoracic Diseases. 2002; 69(6): 543-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12457009

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Accuracy of D-dimer/fibrinogen ratio to predict pulmonary embolism: a prospective diagnostic study. Author(s): Kucher N, Kohler HP, Dornhofer T, Wallmann D, Lammle B. Source: Journal of Thrombosis and Haemostasis : Jth. 2003 April; 1(4): 708-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12871404

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ACEP releases clinical policy on evaluation and management of pulmonary embolism. Author(s): Neff MJ; ACEP. Source: American Family Physician. 2003 August 15; 68(4): 759-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12952389

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Acute pulmonary embolism due to the rupture of a right ventricle hydatic cyst. Author(s): Lahdhili H, Hachicha S, Ziadi M, Thameur H. Source: European Journal of Cardio-Thoracic Surgery : Official Journal of the European Association for Cardio-Thoracic Surgery. 2002 September; 22(3): 462-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12204747

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Acute pulmonary embolism: don't ignore the platelet. Author(s): Sobieszczyk P, Fishbein MC, Goldhaber SZ. Source: Circulation. 2002 October 1; 106(14): 1748-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12356622

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Acute pulmonary embolism: part I: epidemiology, pathophysiology, and diagnosis. Author(s): Goldhaber SZ, Elliott CG. Source: Circulation. 2003 December 2; 108(22): 2726-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14656907

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•

Acute pulmonary embolism: part II: risk stratification, treatment, and prevention. Author(s): Goldhaber SZ, Elliott CG. Source: Circulation. 2003 December 9; 108(23): 2834-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14662690

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Acute symptomatic pulmonary embolism associated with long haul air travel to Sydney. Author(s): Hertzberg SR, Roy S, Hollis G, Brieger D, Chan A, Walsh W. Source: Vascular Medicine (London, England). 2003; 8(1): 21-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12866608

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Advances in diagnosing and excluding pulmonary embolism: spiral CT and D-dimer measurement. Author(s): Carman TL, Deitcher SR. Source: Cleve Clin J Med. 2002 September; 69(9): 721-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12222977

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Advances in the diagnosis and treatment of pulmonary embolism. Pulmonary embolism--how can you mend a broken clot? Author(s): Kroegel C. Source: Respiration; International Review of Thoracic Diseases. 2003 January-February; 70(1): 4-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12584386

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An automated method for the detection of pulmonary embolism in V/Q-scans. Author(s): Frigyesi A. Source: Medical Image Analysis. 2003 September; 7(3): 341-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12946472

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Applications of percutaneous mechanical thrombectomy in pulmonary embolism. Author(s): Fava M, Loyola S. Source: Techniques in Vascular and Interventional Radiology. 2003 March; 6(1): 53-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12772130

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Asymptomatic diffuse pulmonary embolism caused by acrylic cement: an unusual complication of percutaneous vertebroplasty. Author(s): Bernhard J, Heini PF, Villiger PM. Source: Annals of the Rheumatic Diseases. 2003 January; 62(1): 85-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12480681

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Bed rest in deep vein thrombosis and the incidence of scintigraphic pulmonary embolism. Author(s): Schellong SM, Schwarz T, Kropp J, Prescher Y, Beuthien-Baumann B, Daniel WG. Source: Thrombosis and Haemostasis. 1999 September; 82 Suppl 1: 127-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10695503

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Bedside diagnostic tests for pulmonary embolism. Author(s): Fink KS, Miller WC. Source: Jama : the Journal of the American Medical Association. 2001 May 9; 285(18): 2326-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11343474

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Bedside diagnostic tests for pulmonary embolism. Author(s): Schuur J. Source: Jama : the Journal of the American Medical Association. 2001 May 9; 285(18): 2326; Author Reply 2327. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11343473

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Bedside noninvasive detection of acute pulmonary embolism in critically ill surgical patients. Author(s): Anderson JT, Owings JT, Goodnight JE. Source: Archives of Surgery (Chicago, Ill. : 1960). 1999 August; 134(8): 869-74; Discussion 874-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10443811

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Before diagnostic testing for pulmonary embolism: estimating the prior probability of disease. Author(s): Eisner MD. Source: The American Journal of Medicine. 2003 February 15; 114(3): 232-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12637139

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Bilateral pulmonary embolism in a patient on clozapine therapy. Author(s): Maynes D. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 2000 April; 45(3): 296-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10779890

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Biochemical and cytologic characteristics of pleural effusions secondary to pulmonary embolism. Author(s): Romero Candeira S, Hernandez Blasco L, Soler MJ, Munoz A, Aranda I. Source: Chest. 2002 February; 121(2): 465-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11834658

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Brain natriuretic peptide as a predictor of adverse outcome in patients with pulmonary embolism. Author(s): ten Wolde M, Tulevski II, Mulder JW, Sohne M, Boomsma F, Mulder BJ, Buller HR. Source: Circulation. 2003 April 29; 107(16): 2082-4. Epub 2003 Apr 21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12707233

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Brain natriuretic peptide predicts right heart failure in patients with acute pulmonary embolism. Author(s): Kruger S, Graf J, Merx MW, Koch KC, Kunz D, Hanrath P, Janssens U. Source: American Heart Journal. 2004 January; 147(1): 60-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14691420

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British Thoracic Society guidelines for the management of suspected acute pulmonary embolism. Author(s): British Thoracic Society Standards of Care Committee Pulmonary Embolism Guideline Development Group. Source: Thorax. 2003 June; 58(6): 470-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12775856

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Bronchial artery dilatation on MDCT scans of patients with acute pulmonary embolism: comparison with chronic or recurrent pulmonary embolism. Author(s): Hasegawa I, Boiselle PM, Hatabu H. Source: Ajr. American Journal of Roentgenology. 2004 January; 182(1): 67-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14684514

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Bronchoalveolar lavage alterations in pulmonary embolism. Author(s): Nakos G, Kitsiouli EI, Lekka ME. Source: American Journal of Respiratory and Critical Care Medicine. 1998 November; 158(5 Pt 1): 1504-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9817700

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Cardiac biomarkers for risk stratification of patients with acute pulmonary embolism. Author(s): Kucher N, Goldhaber SZ. Source: Circulation. 2003 November 4; 108(18): 2191-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14597581

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Cardiac biomarkers in pulmonary embolism. Author(s): Goldhaber SZ. Source: Chest. 2003 June; 123(6): 1782-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12796147

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Cardiac troponin T monitoring identifies high-risk group of normotensive patients with acute pulmonary embolism. Author(s): Pruszczyk P, Bochowicz A, Torbicki A, Szulc M, Kurzyna M, Fijalkowska A, Kuch-Wocial A. Source: Chest. 2003 June; 123(6): 1947-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12796172

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Clinical outcomes in patients with suspected acute pulmonary embolism and negative helical computed tomographic results in whom anticoagulation was withheld. Author(s): Donato AA, Scheirer JJ, Atwell MS, Gramp J, Duszak R Jr. Source: Archives of Internal Medicine. 2003 September 22; 163(17): 2033-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14504116

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Clinical practice. The evaluation of suspected pulmonary embolism. Author(s): Fedullo PF, Tapson VF. Source: The New England Journal of Medicine. 2003 September 25; 349(13): 1247-56. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14507950

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Clinical usefulness and prognostic value of elevated cardiac troponin I levels in acute pulmonary embolism. Author(s): Mehta NJ, Jani K, Khan IA. Source: American Heart Journal. 2003 May; 145(5): 821-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12766738

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Clozapine and pulmonary embolism. Author(s): Pan R, John V, Hagg S. Source: Acta Psychiatrica Scandinavica. 2003 July; 108(1): 76-7; Discussion 77. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12807382

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Comparison of diagnostic accuracies in outpatients and hospitalized patients of Ddimer testing for the evaluation of suspected pulmonary embolism. Author(s): Schrecengost JE, LeGallo RD, Boyd JC, Moons KG, Gonias SL, Rose CE Jr, Bruns DE. Source: Clinical Chemistry. 2003 September; 49(9): 1483-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12928229

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Comparison of different echocardiographic indexes secondary to right ventricular obstruction in acute pulmonary embolism. Author(s): Mansencal N, Joseph T, Vieillard-Baron A, Qanadli SD, Jondeau G, Lacombe P, Jardin F, Dubourg O. Source: The American Journal of Cardiology. 2003 July 1; 92(1): 116-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12842266

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Comparison of doses for pulmonary embolism detection with helical CT and pulmonary angiography. Author(s): Resten A, Mausoleo F, Valero M, Musset D. Source: European Radiology. 2003 July; 13(7): 1515-21. Epub 2002 July 04. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12835962

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Comparison of interpretations of CT angiograms in the evaluation of suspected pulmonary embolism by on-call radiology fellows and subsequently by radiology faculty. Author(s): Ginsberg MS, King V, Panicek DM. Source: Ajr. American Journal of Roentgenology. 2004 January; 182(1): 61-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14684513

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Computed tomography of acute pulmonary embolism. Author(s): MacDonald SL, Mayo JR. Source: Semin Ultrasound Ct Mr. 2003 August; 24(4): 217-31. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12954005

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Contrast medium injection optimisation in spiral CT for the diagnosis of pulmonary embolism. Author(s): Gattoni F, Tagliaferri B, Scali P, Brioschi S, Boioli F. Source: Radiol Med (Torino). 2003 May-June; 105(5-6): 416-24. English, Italian. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12949452

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Cost-effectiveness of computed tomography in diagnosis of pulmonary embolism. Author(s): Lipchik RJ, Goodman LR. Source: American Journal of Respiratory and Critical Care Medicine. 2004 January 1; 169(1): 129; Author Reply 129-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14695108

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Cost-effectiveness of the bird's nest filter for preventing pulmonary embolism among patients with malignant brain tumors and deep venous thrombosis of the lower extremities. Author(s): Chau Q, Cantor SB, Caramel E, Hicks M, Kurtin D, Grover T, Elting LS. Source: Supportive Care in Cancer : Official Journal of the Multinational Association of Supportive Care in Cancer. 2003 December; 11(12): 795-9. Epub 2003 September 13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=13680322

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Cost-effectiveness of ultrasound in preventing femoral venous catheter-associated pulmonary embolism. Author(s): Cox CE, Carson SS, Biddle AK. Source: American Journal of Respiratory and Critical Care Medicine. 2003 December 15; 168(12): 1481-7. Epub 2003 July 31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12893647

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CT angiography for diagnosis of pulmonary embolism: state of the art. Author(s): Schoepf UJ, Costello P. Source: Radiology. 2004 February; 230(2): 329-37. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14752178

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CT detection of pulmonary embolism in a patient with negative pulmonary angiogram. Author(s): Romano M, Mainenti PP, Imbriaco M, Tamburrini O, Salvatore M. Source: Radiol Med (Torino). 2003 March; 105(3): 234-7. English, Italian. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12835647

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CT perfusion imaging of the lung in pulmonary embolism. Author(s): Herzog P, Wildberger JE, Niethammer M, Schaller S, Schoepf UJ. Source: Academic Radiology. 2003 October; 10(10): 1132-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14587631

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CT pulmonary angiography and suspected acute pulmonary embolism. Author(s): Enden T, Klow NE. Source: Acta Radiologica (Stockholm, Sweden : 1987). 2003 May; 44(3): 310-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12752003

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D-dimer tests for assessment of patients with suspected pulmonary embolism. Author(s): Caine GJ, Lip GY. Source: Archives of Internal Medicine. 2003 January 27; 163(2): 243. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12546620

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Decreased plasma neurohormones and improved cardiac performance after surgical treatment of chronic pulmonary embolism. Author(s): Tulevski II, Bresser P, Hirsch A, Groenink M, Channick RN, Jamieson SW, Mulder BJ. Source: The Annals of Thoracic Surgery. 2003 July; 76(1): 287-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12842565

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Detection of central pulmonary embolism on computed tomography densitometry images before computed tomography pulmonary angiography. Author(s): Kanne JP, Thoongsuwan N, Stern EJ. Source: Journal of Computer Assisted Tomography. 2003 November-December; 27(6): 907-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14600459

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Detection of pulmonary embolism: comparison of paddlewheel and coronal CT reformations--initial experience. Author(s): Chiang EE, Boiselle PM, Raptopoulos V, Reynolds KF, Rosen MP, Simon M. Source: Radiology. 2003 August; 228(2): 577-82. Epub 2003 June 20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12819339

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Diagnosing and managing acute pulmonary embolism: role of cardiac troponins. Author(s): Tapson VF. Source: American Heart Journal. 2003 May; 145(5): 751-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12766729

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Diagnosing pulmonary embolism in outpatients with clinical assessment, D-dimer measurement, venous ultrasound, and helical computed tomography: a multicenter management study. Author(s): Perrier A, Roy PM, Aujesky D, Chagnon I, Howarth N, Gourdier AL, Leftheriotis G, Barghouth G, Cornuz J, Hayoz D, Bounameaux H. Source: The American Journal of Medicine. 2004 March 1; 116(5): 291-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14984813

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Diagnosing pulmonary embolism in primary care. Author(s): Rossdale M, Harvey JE. Source: Bmj (Clinical Research Ed.). 2003 August 16; 327(7411): 393. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12920003

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Diagnosing pulmonary embolism: a question of too much choice? Author(s): Mountain D. Source: Emergency Medicine (Fremantle, W.A.). 2003 June; 15(3): 250-62. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12786647

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Diagnosis of posttraumatic pulmonary embolism: is chest computed tomographic angiography acceptable? Author(s): Anderson JT, Jenq T, Bain M, Jacoby R, Osnis R, Gosselin RC, Owings JT. Source: The Journal of Trauma. 2003 March; 54(3): 472-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12634525

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Diagnosis of pulmonary embolism with helical C.T. scan. Author(s): Usman MU, Bari V, Yaqoob J, Murad M. Source: J Pak Med Assoc. 2003 August; 53(8): 354-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14558741

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Diagnosis of pulmonary embolism with spiral CT as a second procedure following scintigraphy. Author(s): van Strijen MJ, de Monye W, Kieft GJ, Pattynama PM, Huisman MV, Smith SJ, Bloem JL. Source: European Radiology. 2003 July; 13(7): 1501-7. Epub 2002 November 19. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12835960

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Diagnosis of pulmonary embolism. Author(s): Kearon C. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 2003 January 21; 168(2): 183-94. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12538548

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Diagnosis of venous thromboembolism: factors determining individual patient probabilities of deep vein thrombosis or pulmonary embolism. Author(s): Ferreira GS, Carson JL. Source: Curr Hematol Rep. 2003 September; 2(5): 423-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12932316

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Diagnostic approaches to suspected deep vein thrombosis and pulmonary embolism. Author(s): Bounameaux H, Perrier A. Source: The Hematology Journal : the Official Journal of the European Haematology Association / Eha. 2003; 4(2): 97-103. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12750727

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Diagnostic strategies for excluding pulmonary embolism in clinical outcome studies. A systematic review. Author(s): Kruip MJ, Leclercq MG, van der Heul C, Prins MH, Buller HR. Source: Annals of Internal Medicine. 2003 June 17; 138(12): 941-51. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12809450

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Diagnostic strategy for patients with suspected pulmonary embolism: a prospective multicentre outcome study. Author(s): Musset D, Parent F, Meyer G, Maitre S, Girard P, Leroyer C, Revel MP, Carette MF, Laurent M, Charbonnier B, Laurent F, Mal H, Nonent M, Lancar R, Grenier P, Simonneau G; Evaluation du Scanner Spirale dans l'Embolie Pulmonaire study group. Source: Lancet. 2002 December 14; 360(9349): 1914-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12493257

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Diagnostic utility of echocardiography in patients with suspected pulmonary embolism. Author(s): Bova C, Greco F, Misuraca G, Serafini O, Crocco F, Greco A, Noto A. Source: The American Journal of Emergency Medicine. 2003 May; 21(3): 180-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12811708

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Differentiation of pulmonary embolism from high altitude pulmonary edema. Author(s): Khan DA, Hashim R, Mirza TM, Rahman MM. Source: J Coll Physicians Surg Pak. 2003 May; 13(5): 267-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12757675

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Donor intracaval thrombus formation and pulmonary embolism after simultaneous piggyback liver transplantation and aortic valve replacement. Author(s): Nishida S, Vaidya A, Franco E, Neff G, Madariaga J, Nakamura N, Levi DM, Nery JR, Bolooki H, Tzakis AG. Source: Clinical Transplantation. 2003 October; 17(5): 465-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14703932

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Duplex ultrasonography in patients suspected of postoperative pulmonary embolism following total joint arthroplasty. Author(s): Della Valle CJ, Steiger DJ, DiCesare PE. Source: Am J Orthop. 2003 August; 32(8): 386-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12943339

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ECG-gated multislice spiral CT for diagnosis of acute pulmonary embolism. Author(s): Marten K, Engelke C, Funke M, Obenauer S, Baum F, Grabbe E. Source: Clinical Radiology. 2003 November; 58(11): 862-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14581010

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Echocardiography in the management of pulmonary embolism. Author(s): Goldhaber SZ. Source: Annals of Internal Medicine. 2002 May 7; 136(9): 691-700. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11992305

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ECMO resuscitation after massive pulmonary embolism during liver transplantation. Author(s): Szocik J, Rudich S, Csete M. Source: Anesthesiology. 2002 September; 97(3): 763-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12218564

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Effectiveness of the ROBODOC system in preventing intraoperative pulmonary embolism. Author(s): Hagio K, Sugano N, Takashina M, Nishii T, Yoshikawa H, Ochi T. Source: Acta Orthopaedica Scandinavica. 2003 June; 74(3): 264-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12899545

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Effects of age on the performance of common diagnostic tests for pulmonary embolism. Author(s): Righini M, Goehring C, Bounameaux H, Perrier A. Source: The American Journal of Medicine. 2000 October 1; 109(5): 357-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11020391

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Efficacy of alteplase thrombolysis for ED treatment of pulmonary embolism with shock. Author(s): Le Conte P, Huchet L, Trewick D, Longo C, Vial I, Batard E, Yatim D, Touze MD, Baron D. Source: The American Journal of Emergency Medicine. 2003 September; 21(5): 438-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14523886

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Electron beam computed tomography and ventilation perfusion scintigraphy in the diagnosis of pulmonary embolism. Author(s): Kettner BI, Enzweiler CN, Sandrock D, Reisinger I, Munz DL. Source: European Journal of Nuclear Medicine and Molecular Imaging. 2002 May; 29(5): 585-90. Epub 2002 February 27. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11976795

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Elevated cardiac troponin levels in patients with submassive pulmonary embolism. Author(s): Douketis JD, Crowther MA, Stanton EB, Ginsberg JS. Source: Archives of Internal Medicine. 2002 January 14; 162(1): 79-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11784223

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Elevated troponin-I in a patient with acute pulmonary embolism without evidence of coronary artery disease. Author(s): Schoondyke JW, Mohan R, Appakondu S, Sandhu D, Downs C, Iskandar S, Ponder M. Source: Tenn Med. 2002 May; 95(5): 190-1. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12012850

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Elevations of B-type natriuretic peptide in pulmonary embolism: a case series. Author(s): Bilkovski RN, Kulstad EB. Source: The Journal of Emergency Medicine. 2003 November; 25(4): 415-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14654183

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ELISA D-dimer measurement for the clinical suspicion of pulmonary embolism in the emergency department: one-year observational study of the safety profile and physician's prescription. Author(s): Fr V, Hainaut P, Fr T, Elamly A, Dessomme B, Lavenne E, Reynaert MS. Source: Acta Clin Belg. 2003 July-August; 58(4): 233-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14635531

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Embolus location affects the sensitivity of a rapid quantitative D-dimer assay in the diagnosis of pulmonary embolism. Author(s): De Monye W, Sanson BJ, Mac Gillavry MR, Pattynama PM, Buller HR, van den Berg-Huysmans AA, Huisman MV; ANTELOPE-Study Group. Source: American Journal of Respiratory and Critical Care Medicine. 2002 February 1; 165(3): 345-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11818319

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Emergent surgery for massive pulmonary embolism on the basis of clinical diagnosis. Author(s): Brevetti GR, O'Brien B, Coomer CL, Hall TS, Brevetti LS, Jablons DM. Source: Texas Heart Institute Journal / from the Texas Heart Institute of St. Luke's Episcopal Hospital, Texas Children's Hospital. 2003; 30(2): 149-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12809261

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Enoxaparin monotherapy without oral anticoagulation to treat acute symptomatic pulmonary embolism. Author(s): Beckman JA, Dunn K, Sasahara AA, Goldhaber SZ. Source: Thrombosis and Haemostasis. 2003 June; 89(6): 953-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12783106

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Estimated incidence of acute pulmonary embolism in a community/teaching general hospital. Author(s): Stein PD, Patel KC, Kalra NK, Petrina M, Savarapu P, Furlong JW Jr, Steele RD Jr, Check FE. Source: Chest. 2002 March; 121(3): 802-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11888963

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Evaluating suspected pulmonary embolism. Author(s): Nokes SR, Hronas T. Source: J Ark Med Soc. 2002 March; 98(9): 298-9. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11881263

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Evaluation of the deep venous system in patients with suspected pulmonary embolism with multi-detector CT: a prospective study in comparison to Doppler sonography. Author(s): Begemann PG, Bonacker M, Kemper J, Guthoff AE, Hahn KE, Steiner P, Adam G. Source: Journal of Computer Assisted Tomography. 2003 May-June; 27(3): 399-409. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12794606

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Excluding pulmonary embolism with helical (spiral) computed tomography: Evidence is catching up with enthusiasm. Author(s): Kearon C. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 2003 May 27; 168(11): 1430-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12771073

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Exclusion and diagnosis of pulmonary embolism by a rapid ELISA D-dimer test and noninvasive imaging techniques within the context of a clinical model. Author(s): Michiels JJ, Pattynama PM. Source: Clinical and Applied Thrombosis/Hemostasis : Official Journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis. 2000 January; 6(1): 46-52. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10726049

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Extended oral anticoagulant therapy after a first episode of pulmonary embolism. Author(s): Agnelli G, Prandoni P, Becattini C, Silingardi M, Taliani MR, Miccio M, Imberti D, Poggio R, Ageno W, Pogliani E, Porro F, Zonzin P; Warfarin Optimal Duration Italian Trial Investigators. Source: Annals of Internal Medicine. 2003 July 1; 139(1): 19-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12834314

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Factor V leiden and morbid obesity in fatal postoperative pulmonary embolism. Author(s): Blaszyk H, Bjornsson J. Source: Archives of Surgery (Chicago, Ill. : 1960). 2000 December; 135(12): 1410-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11115343

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Factor V Leiden paradox: risk of deep-vein thrombosis but not of pulmonary embolism. Author(s): Bounameaux H. Source: Lancet. 2000 July 15; 356(9225): 182-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10963193

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Factors V leiden and II 20210A in patients with symptomatic pulmonary embolism and deep vein thrombosis. Author(s): Meyer G, Emmerich J, Helley D, Arnaud E, Nicaud V, Alhenc-Gelas M, Aiach M, Fischer A, Sors H, Fiessinger JN. Source: The American Journal of Medicine. 2001 January; 110(1): 12-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11152859

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Fatal intra-operative pulmonary embolism following application of an Esmarch bandage. Author(s): Darmanis S, Papanikolaou A, Pavlakis D. Source: Injury. 2002 November; 33(9): 761-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12379384

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Fatal pulmonary embolism after atrial septal defect closure in a paediatric patient. Author(s): Busch T, Lotfi S, Sirbu H, Aleksic I, Ruschewski W. Source: Scandinavian Cardiovascular Journal : Scj. 1999; 33(3): 187-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10399810

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Fatal pulmonary embolism after total hip arthroplasty. Three Japanese cases. Author(s): Kawanabe K, Iida H, Nishimatsu H, Wadayama B, Yoshikawa J, Nakamura T. Source: Bull Hosp Jt Dis. 1997; 56(4): 211-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9438081

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Fatal pulmonary embolism and mortality after revision of failed total hip arthroplasties. Author(s): Wroblewski BM, Siney PD, Fleming PA. Source: The Journal of Arthroplasty. 2000 June; 15(4): 437-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10884202

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Fatal pulmonary embolism immediately after transatlantic air travel to the United States: less than one in a million. Author(s): Kline JA, Putman M, Courtney DM. Source: Thrombosis and Haemostasis. 2002 February; 87(2): 342. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11858497

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Fatal pulmonary embolism in a child undergoing extra-ventricular drainage surgery-a case report. Author(s): Sung CS, Chow LH, Sun MS, Yu HP, Ho CM, Tsou MY, Lee TY. Source: Acta Anaesthesiol Sin. 1999 March; 37(1): 35-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10407526

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Fatal pulmonary embolism in hospitalized patients. Clinical diagnosis versus pathological confirmation. Author(s): Mesquita CT, Morandi Junior JL, Perrone FT, Oliveira Cda S, Barreira LJ, Nascimento SS, Pareto Junior RC, Mesquita ET. Source: Arquivos Brasileiros De Cardiologia. 1999 September; 73(3): 251-8. English, Portuguese. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10752164

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Fatal pulmonary embolism: a study of genetic and acquired factors. Author(s): Slovacek KJ, Harris AF, Greene JF Jr, Rao A. Source: Molecular Diagnosis : a Journal Devoted to the Understanding of Human Disease Through the Clinical Application of Molecular Biology. 2000 March; 5(1): 53-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10837090

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Fever in acute pulmonary embolism. Author(s): Stein PD, Afzal A, Henry JW, Villareal CG. Source: Chest. 2000 January; 117(1): 39-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10631196

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Fibrin monomer could be a useful predictor of pulmonary embolism after total hip arthroplasty: preliminary report. Author(s): Kubo T, Kitajima I, Makinodan A, Niratsuka S, Inoue S, Otsuka G, Ohashi S, Ueshima K, Hirasawa Y. Source: Journal of Orthopaedic Science : Official Journal of the Japanese Orthopaedic Association. 2001; 6(2): 119-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11484095

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First trimester use of recombinant tissue plasminogen activator in pulmonary embolism. Author(s): Huang WH, Kirz DS, Gallee RC, Gordey K. Source: Obstetrics and Gynecology. 2000 November; 96(5 Pt 2): 838. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11094230

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Follow-up of perfusion defects in pulmonary perfusion scanning after pulmonary embolism: are we too careless? Author(s): Gotthardt M, Schipper M, Franzius C, Behe M, Barth A, Schurrat T, Hoffken H, Gratz S, Joseph K, Behr TM. Source: Nuclear Medicine Communications. 2002 May; 23(5): 447-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11973485

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Fondaparinux in pulmonary embolism. Author(s): Wertz J. Source: The New England Journal of Medicine. 2004 February 5; 350(6): 619. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14762195

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Fragmentation of a right atrial myxoma presenting as a pulmonary embolism. Author(s): Idir M, Oysel N, Guibaud JP, Labouyrie E, Roudaut R. Source: Journal of the American Society of Echocardiography : Official Publication of the American Society of Echocardiography. 2000 January; 13(1): 61-3. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10625833

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Fragmentation of massive pulmonary embolism by pigtail rotation catheter: possible complication. Author(s): Schmitz-Rode T, Janssens U, Hanrath P, Gunther RW. Source: European Radiology. 2001; 11(10): 2047-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11702140

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Frequency of major hemorrhage in patients treated with unfractionated intravenous heparin for deep venous thrombosis or pulmonary embolism: a study in routine clinical practice. Author(s): Zidane M, Schram MT, Planken EW, Molendijk WH, Rosendaal FR, van der Meer FJ, Huisman MV. Source: Archives of Internal Medicine. 2000 August 14-28; 160(15): 2369-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10927736

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Frequency of myocardial infarction, pulmonary embolism, deep venous thrombosis, and death following primary hip or knee arthroplasty. Author(s): Mantilla CB, Horlocker TT, Schroeder DR, Berry DJ, Brown DL. Source: Anesthesiology. 2002 May; 96(5): 1140-6. Erratum In: Anesthesiology 2002 August; 97(2): 531. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11981154

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Gadolinium-enhanced magnetic resonance angiography for detection of acute pulmonary embolism: an in-depth review. Author(s): Stein PD, Woodard PK, Hull RD, Kayali F, Weg JG, Olson RE, Fowler SE. Source: Chest. 2003 December; 124(6): 2324-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14665516

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Gated myocardial perfusion scan leading to diagnosis of unsuspected massive pulmonary embolism. Author(s): Soudry G, Dibos PE. Source: Annals of Internal Medicine. 2000 May 16; 132(10): 845. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10819719

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Gender-associated findings in postmortem examinations of elderly patients: an increased rate of pulmonary embolism in women. Author(s): Leibovitz A, Blumenfeld O, Segal R, Lubart E, Baumoehl Y, Habot B. Source: Isr Med Assoc J. 2003 May; 5(5): 340-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12811951

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Genetic polymorphisms associated with acute pulmonary embolism and deep venous thrombosis. Author(s): Nizankowska-Mogilnicka E, Adamek L, Grzanka P, Domagala TB, Sanak M, Krzanowski M, Szczeklik A. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2003 January; 21(1): 25-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12570104

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Genetics and pulmonary medicine. 4. Pulmonary embolism. Author(s): Laffan M. Source: Thorax. 1998 August; 53(8): 698-702. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9828859

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Geriatrics photo quiz. Pulmonary embolism. Author(s): Shua-Haim JR, Gross JS. Source: Geriatrics. 1997 July; 52(7): 29, 77. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9230870

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Guidelines on pulmonary embolism. Author(s): Davies CW. Source: Thorax. 1998 July; 53(7): 625. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9797770

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Guidelines on the diagnosis of acute pulmonary embolism and their applicability in clinical practice. Author(s): Rubboli A, Euler DE. Source: European Heart Journal. 2001 May; 22(9): 798-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11350114

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Head injury and pulmonary embolism: a retrospective report based on the Pennsylvania Trauma Outcomes study. Author(s): Page RB, Spott MA, Krishnamurthy S, Taleghani C, Chinchilli VM. Source: Neurosurgery. 2004 January; 54(1): 143-8; Discussion 148-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14683551

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Helical computed tomography and magnet resonance imaging: diagnosis of pulmonary embolism in symptomatic patients. Author(s): Blevins S, Edwards S, Raskob G. Source: Current Opinion in Hematology. 2003 September; 10(5): 345-50. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12913788

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Helical computed tomography and the diagnosis of pulmonary embolism. Author(s): Bates SM, Ginsberg JS. Source: Annals of Internal Medicine. 2000 February 1; 132(3): 240-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10651607

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Helical computed tomography as a test for pulmonary embolism. Author(s): Perrier A, Bounameaux H. Source: Annals of Internal Medicine. 2003 December 2; 139(11): 955-6; Author Reply 956. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14644902

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Helical computed tomography for diagnosing pulmonary embolism. Author(s): Mayo JR, Baile EM, Pare PD. Source: Annals of Internal Medicine. 2000 September 19; 133(6): 483-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10975975

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Helical CT for the evaluation of suspected acute pulmonary embolism: diagnostic pitfalls. Author(s): Gotway MB, Patel RA, Webb WR. Source: Journal of Computer Assisted Tomography. 2000 March-April; 24(2): 267-73. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10752891

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Helical CT pulmonary angiography predictors of in-hospital morbidity and mortality in patients with acute pulmonary embolism. Author(s): Araoz PA, Gotway MB, Trowbridge RL, Bailey RA, Auerbach AD, Reddy GP, Dawn SK, Webb WR, Higgins CB. Source: Journal of Thoracic Imaging. 2003 October; 18(4): 207-16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14561905

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Helical CT scanning in the diagnosis of pulmonary embolism. Author(s): Garg K, Macey L. Source: Respiration; International Review of Thoracic Diseases. 2003 May-June; 70(3): 231-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12915739

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Heparin plus alteplase compared with heparin alone in patients with submassive pulmonary embolism. Author(s): Haire WD. Source: Curr Hematol Rep. 2003 September; 2(5): 405-6. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12932312

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Heparin plus alteplase compared with heparin alone in patients with submassive pulmonary embolism. Author(s): Konstantinides S, Geibel A, Heusel G, Heinrich F, Kasper W; Management Strategies and Prognosis of Pulmonary Embolism-3 Trial Investigators. Source: The New England Journal of Medicine. 2002 October 10; 347(15): 1143-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12374874

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Heparin, low molecular weight heparin and physical methods for preventing deep vein thrombosis and pulmonary embolism following surgery for hip fractures. Author(s): Handoll HH, Farrar MJ, McBirnie J, Tytherleigh-Strong G, Milne AA, Gillespie WJ. Source: Cochrane Database Syst Rev. 2002; (4): Cd000305. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12519540

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Heparin, low molecular weight heparin and physical methods for preventing deep vein thrombosis and pulmonary embolism following surgery for hip fractures. Author(s): Handoll HH, Farrar MJ, McBirnie J, Tytherleigh-Strong G, Awal KA, Milne AA, Gillespie WJ. Source: Cochrane Database Syst Rev. 2000; (2): Cd000305. Review. Update In: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10796339

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Heparin-induced thrombocytopenia type II with pulmonary embolism after cesarean section. Author(s): Meyberg R, Ertan AK, Axt R, Villena-Heinsen C, Schmidt W, Friedrich M. Source: Clin Exp Obstet Gynecol. 2000; 27(1): 33-4. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10758796

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Heparin-induced thrombocytopenia with pulmonary embolism and disseminated intravascular coagulation associated with low-molecular-weight heparin. Author(s): Betrosian AP, Theodossiades G, Lambroulis G, Kostantonis D, Balla M, Papanikolaou M, Georgiades G. Source: The American Journal of the Medical Sciences. 2003 January; 325(1): 45-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12544086

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High dose and short-term streptokinase infusion in patients with pulmonary embolism: prospective with seven-year follow-up trial. Author(s): Jerjes-Sanchez C, Ramirez-Rivera A, Arriaga-Nava R, Iglesias-Gonzalez S, Gutierrez P, Ibarra-Perez C, Martinez A, Valencia S, Rosado-Buzzo A, Pierzo JA, Rosas E. Source: Journal of Thrombosis and Thrombolysis. 2001 December; 12(3): 237-47. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11981107

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High prevalence of detectable deep venous thrombosis in patients with acute pulmonary embolism. Author(s): Girard P, Musset D, Parent F, Maitre S, Phlippoteau C, Simonneau G. Source: Chest. 1999 October; 116(4): 903-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10531151

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How accurate is the D-dimer assay in diagnosing pulmonary embolism? Author(s): Damek HA Jr, Lindbloom EJ. Source: The Journal of Family Practice. 2002 November; 51(11): 919. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12485540

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How we do it: pulmonary embolism. Author(s): Horton KM. Source: Critical Reviews in Computed Tomography. 2002; 43(2): 69-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12233914

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How well can radiologists using neural network software diagnose pulmonary embolism? Author(s): Scott JA, Palmer EL, Fischman AJ. Source: Ajr. American Journal of Roentgenology. 2000 August; 175(2): 399-405. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10915682

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Hyperhomocysteinemia masquerading as pulmonary embolism. Author(s): Dani SI, Thanvi S, Shah JM, Prajapti J, Jain S, Joshi H. Source: J Assoc Physicians India. 2003 September; 51: 914-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14710983

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Images in cardiology: coexisting pulmonary embolism and abdominal aortic dissection. Author(s): Gupta R, Uhrbrock D, Birnbaum Y. Source: Clin Cardiol. 2003 August; 26(8): 395. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12918643

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Images in clinical medicine. Thrombolysis of a massive pulmonary embolism. Author(s): Fam NP, Verma A. Source: The New England Journal of Medicine. 2002 October 10; 347(15): 1161. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12374876

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Images in clinical radiology. Diagnosis of pulmonary embolism with 16-slice CT. Author(s): Salovic D, Humblet Y, Coche E. Source: Jbr-Btr. 2003 March-April; 86(2): 113. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12839425

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Impact of morphologic characteristics of central pulmonary thromboemboli in massive pulmonary embolism. Author(s): Podbregar M, Krivec B, Voga G. Source: Chest. 2002 September; 122(3): 973-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12226042

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Importance of cardiac troponins I and T in risk stratification of patients with acute pulmonary embolism. Author(s): Konstantinides S, Geibel A, Olschewski M, Kasper W, Hruska N, Jackle S, Binder L. Source: Circulation. 2002 September 3; 106(10): 1263-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12208803

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In patients symptomatic for deep-vein thrombosis factor VIII elevation is found twice as frequent as in patients symptomatic for pulmonary embolism. Author(s): Bombeli T, de Conno E, Jutzi M, Fehr J. Source: Thrombosis and Haemostasis. 2003 January; 89(1): 198-200. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12540971

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Incidence of air travel-related pulmonary embolism at the Madrid-Barajas airport. Author(s): Perez-Rodriguez E, Jimenez D, Diaz G, Perez-Walton I, Luque M, Guillen C, Manas E, Yusen RD. Source: Archives of Internal Medicine. 2003 December 8-22; 163(22): 2766-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14662631

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Incidence of clinically unsuspected pulmonary embolism in mechanically ventilated lung transplant recipients. Author(s): Burns KE, Iacono AT. Source: Transplantation. 2003 September 27; 76(6): 964-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14508362

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Incidence rates of dislocation, pulmonary embolism, and deep infection during the first six months after elective total hip replacement. Author(s): Phillips CB, Barrett JA, Losina E, Mahomed NN, Lingard EA, Guadagnoli E, Baron JA, Harris WH, Poss R, Katz JN. Source: The Journal of Bone and Joint Surgery. American Volume. 2003 January; 85-A(1): 20-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12533567

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Increased prevalence of coronary artery calcification in patients with suspected pulmonary embolism. Author(s): Kiryu S, Raptopoulos V, Baptista J, Hatabu H. Source: Academic Radiology. 2003 August; 10(8): 840-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12945917

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Increasing mortality from pulmonary embolism in Japan, 1951-2000. Author(s): Sakuma M, Konno Y, Shirato K. Source: Circulation Journal : Official Journal of the Japanese Circulation Society. 2002 December; 66(12): 1144-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12499622

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Incremental prognostic value of troponin I and echocardiography in patients with acute pulmonary embolism. Author(s): Kucher N, Wallmann D, Carone A, Windecker S, Meier B, Hess OM. Source: European Heart Journal. 2003 September; 24(18): 1651-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14499227

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In-hospital and long-term outcome after sub-massive and massive pulmonary embolism submitted to thrombolytic therapy. Author(s): Meneveau N, Ming LP, Seronde MF, Mersin N, Schiele F, Caulfield F, Bernard Y, Bassand JP. Source: European Heart Journal. 2003 August; 24(15): 1447-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12909074

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Insertion of an inferior venocaval filter in a pregnant woman at risk for pulmonary embolism-- a challenging management. Author(s): Reddy K, Reginald PW, Charig MJ. Source: Journal of Obstetrics and Gynaecology : the Journal of the Institute of Obstetrics and Gynaecology. 2003 March; 23(2): 198. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12751510

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Intra-atrial thrombosis and pulmonary embolism complicating pacemaker leads for cardiac resynchronization therapy. Author(s): Sbragia P, Nait-Saidi L, Trigano JA, Saadjian A, Barnay P, Levy S. Source: Journal of Interventional Cardiac Electrophysiology : an International Journal of Arrhythmias and Pacing. 2003 August; 9(1): 25-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12975567

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Intraoperative pulmonary embolism during spinal instrumentation surgery. A prospective study using transoesophageal echocardiography. Author(s): Ann Intern Med. 2003 Feb 18;138(4):I58 Source: The Journal of Bone and Joint Surgery. British Volume. 2003 January; 85(1): 90-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12585850

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Intrapulmonary thrombolytic therapy in a child with acute pulmonary embolism due to primary antiphospholipid syndrome. Author(s): Huang HJ, Wang JN, Tsai YC, Lin CS, Wu JM. Source: Acta Paediatr Taiwan. 2002 November-December; 43(6): 351-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12632791

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Intrathoracic blood volume in a patient with pulmonary embolism. Author(s): Sakka SG, Meier-Hellmann A. Source: European Journal of Anaesthesiology. 2003 March; 20(3): 256-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12650499

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Is a lung perfusion scan obtained by using single photon emission computed tomography able to improve the radionuclide diagnosis of pulmonary embolism? Author(s): Collart JP, Roelants V, Vanpee D, Lacrosse M, Trigaux JP, Delaunois L, Gillet JB, De Coster P, Vander Borght T. Source: Nuclear Medicine Communications. 2002 November; 23(11): 1107-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12411840

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Is there a place for inhaled nitric oxide in the therapy of acute pulmonary embolism? Author(s): Tanus-Santos JE, Theodorakis MJ. Source: American Journal of Respiratory Medicine : Drugs, Devices, and Other Interventions. 2002; 1(3): 167-76. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14720054

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JAMA patient page. Pulmonary embolism. Author(s): Parmet S, Lynm C, Glass RM. Source: Jama : the Journal of the American Medical Association. 2003 December 3; 290(21): 2898. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14657080

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Jet “leg”, pulmonary embolism, and hypoxia. Author(s): James PB. Source: Lancet. 1996 June 15; 347(9016): 1697. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8642987

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Jet leg, pulmonary embolism, and hypoxia. Author(s): Simons R, Krol J. Source: Lancet. 1996 August 10; 348(9024): 416. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8709773

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Jet leg, pulmonary embolism, and hypoxia. Author(s): Bagshaw M. Source: Lancet. 1996 August 10; 348(9024): 415-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8709771

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Krypton-81m ventilation and technetium-99m macroaggregated albumin perfusion scintigraphy for detection of pulmonary embolism: the first experience in Taiwan. Author(s): Cherng SC, Yang SP, Wang YF, Jen TK, Huang WS, Lo AR. Source: Zhonghua Yi Xue Za Zhi (Taipei). 2000 December; 63(12): 876-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11195138

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Laboratory tests in the diagnosis of pulmonary embolism. Author(s): Meyer G, Roy PM, Sors H, Sanchez O. Source: Respiration; International Review of Thoracic Diseases. 2003 March-April; 70(2): 125-32. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12740506

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Large right atrial thrombus with pulmonary embolism. Author(s): Hung MJ, Wang CH, Kuo LT, Cherng WJ. Source: Echocardiography (Mount Kisco, N.Y.). 2000 May; 17(4): 329-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10979001

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Large thrombus at the site of primary sutured atrial septal defect associated with pulmonary embolism and treatment by thrombolysis. Author(s): Dinckal MH, Davutoglu V, Soydinc S, Akdemir I, Aksoy M. Source: Echocardiography (Mount Kisco, N.Y.). 2003 August; 20(6): 535-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12859367

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Left atrial thrombus causing pulmonary embolism by passing through an atrial septal defect. Author(s): Ishihara Y, Hara H, Saijo T, Namiki A, Suzuki M, Hirai H, Yamaguchi T. Source: Circulation Journal : Official Journal of the Japanese Circulation Society. 2002 January; 66(1): 109-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11999658

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Left atrial tumour mimicking pulmonary embolism. Author(s): Seal EC, Rutter HR, Horrigan MC, Britton MG. Source: Respiratory Medicine. 1997 October; 91(9): 562-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9415358

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Left sided pulmonary embolism mimicking non Q acute myocardial infarction. Author(s): Wadhwa S. Source: J Assoc Physicians India. 2001 March; 49: 353-6. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11291976

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Lessening the diagnostic uncertainty in patients with suspected pulmonary embolism. Author(s): Hull RD, Ghali WA, Pineo GF. Source: The American Journal of Medicine. 2004 March 1; 116(5): 352-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14984823

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Lethal heparin-associated pulmonary embolism--case reports. Author(s): Claeys LG. Source: Angiology. 2002 July-August; 53(4): 475-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12143956

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Liver abscess and Aeromonas bacteremia with septic pulmonary embolism. Author(s): Kamano Y, Ohashi H, Kikuchi T, Watanabe K, Kitahara M. Source: Intern Med. 2003 October; 42(10): 1047-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14606725

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Long-term benefit of thrombolytic therapy in patients with pulmonary embolism. Author(s): Sharma GV, Folland ED, McIntyre KM, Sasahara AA. Source: Vascular Medicine (London, England). 2000; 5(2): 91-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10943585

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Low molecular weight heparin in the treatment of acute deep vein thrombosis and pulmonary embolism: A paradigm change in care. Author(s): Merli GJ. Source: Journal of Thrombosis and Thrombolysis. 2000 June; 9 Suppl 1: S21-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10859581

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Low pro-brain natriuretic peptide levels predict benign clinical outcome in acute pulmonary embolism. Author(s): Kucher N, Printzen G, Doernhoefer T, Windecker S, Meier B, Hess OM. Source: Circulation. 2003 April 1; 107(12): 1576-8. Epub 2003 March 24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12668488

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Low-molecular weight heparin for treatment of pulmonary embolism in a pregnant woman. Author(s): Laifer SA, Stiller RJ, Dunston-Boone G, Whetham JC. Source: Thrombosis and Haemostasis. 1999 October; 82(4): 1361-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10544931

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Low-molecular-weight heparin compared with intravenous unfractionated heparin for treatment of pulmonary embolism: a meta-analysis of randomized, controlled trials. Author(s): Quinlan DJ, McQuillan A, Eikelboom JW. Source: Annals of Internal Medicine. 2004 February 3; 140(3): 175-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14757615

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Low-molecular-weight heparin in the treatment of pulmonary embolism. Author(s): Ageno W, Turpie AG. Source: Semin Vasc Surg. 2000 September; 13(3): 189-93. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11005462

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Low-molecular-weight heparin vs heparin in the treatment of patients with pulmonary embolism. American-Canadian Thrombosis Study Group. Author(s): Hull RD, Raskob GE, Brant RF, Pineo GF, Elliott G, Stein PD, Gottschalk A, Valentine KA, Mah AF. Source: Archives of Internal Medicine. 2000 January 24; 160(2): 229-36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10647762

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Low-molecular-weight heparins versus unfractionated heparin in the treatment of deep vein thrombosis and pulmonary embolism. Author(s): Merli GJ. Source: American Journal of Physical Medicine & Rehabilitation / Association of Academic Physiatrists. 2000 September-October; 79(5 Suppl): S9-16. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10994898

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Lung scan in the diagnosis and management of patent foramen ovale pulmonary embolism, paradoxical embolism. Author(s): Civelek AC, Ozalp E, Gerber BL, Weiss J. Source: Clinical Imaging. 2002 September-October; 26(5): 349-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12213371

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Lung scintigraphy and helical computed tomography for the diagnosis of pulmonary embolism: a meta-analysis. Author(s): van Beek EJ, Brouwers EM, Song B, Bongaerts AH, Oudkerk M. Source: Clinical and Applied Thrombosis/Hemostasis : Official Journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis. 2001 April; 7(2): 87-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11292198

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Lung sonography in pulmonary embolism. Author(s): Lichtenstein DA, Loubieres Y. Source: Chest. 2003 June; 123(6): 2154; Author Reply 2154-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12796205

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Major bleeding complications in cardiopulmonary resuscitation: the place of thrombolytic therapy in cardiac arrest due to massive pulmonary embolism. Author(s): Janata K, Holzer M, Kurkciyan I, Losert H, Riedmuller E, Pikula B, Laggner AN, Laczika K. Source: Resuscitation. 2003 April; 57(1): 49-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12668299

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Major pulmonary embolism and shock. Persistent hypotension after thrombolysis treated with improvised mechanical fragmentation of thrombus. Author(s): Lapanun W, Walters DL, McCarthy J, Burstow DJ. Source: The Medical Journal of Australia. 2003 November 3; 179(9): 495-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14583082

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Making a diagnosis of pulmonary embolism--new methods and clinical issues. Author(s): Iles S, Beckert L, Than M, Town I. Source: N Z Med J. 2003 July 11; 116(1177): U499. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12861313

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Management of pulmonary embolism during acrylic vertebroplasty. Author(s): Tozzi P, Abdelmoumene Y, Corno AF, Gersbach PA, Hoogewoud HM, von Segesser LK. Source: The Annals of Thoracic Surgery. 2002 November; 74(5): 1706-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12440642

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Managing pulmonary embolism. Author(s): Janata K. Source: Bmj (Clinical Research Ed.). 2003 June 21; 326(7403): 1341-2. Erratum In: Bmj. 2003 July 19; 327(7407): 160. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12816796

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Massive pulmonary embolism and pharmacological-mechanical thrombolysis: report of a case treated by mechanical catheter fragmentation. Author(s): Pieri S, Morucci M, Agresti P, De' Medici L. Source: Radiol Med (Torino). 2003 July-August; 106(1-2): 108-13. English, Italian. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12951558

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Massive pulmonary embolism due to late-onset heparin-induced thrombocytopenia following coronary artery bypass graft surgery: successful treatment with lepirudin. Author(s): Badmanaban B, Sachithanandan A, Hunter I, Graham A, Sarsam M. Source: Journal of Cardiac Surgery. 2003 July-August; 18(4): 316-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12869178

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Massive pulmonary embolism presenting as complete unilateral absence of lung perfusion on pulmonary scintigraphy: correlative imaging with angiography and computed tomography. Author(s): Hod N, Peer A, Mindlin L, Ramot Y, Vazina A, Horne T. Source: Clinical Nuclear Medicine. 2003 January; 28(1): 34-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12493958

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Massive pulmonary embolism: a remarkable case and review of treatment. Author(s): Cooper JM, Beckman JA. Source: Vascular Medicine (London, England). 2002 August; 7(3): 181-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12553741

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Mechanical and enzymatic thrombolysis for massive pulmonary embolism. Author(s): De Gregorio MA, Gimeno MJ, Mainar A, Herrera M, Tobio R, Alfonso R, Medrano J, Fava M. Source: Journal of Vascular and Interventional Radiology : Jvir. 2002 February; 13(2 Pt 1): 163-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11830622

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Mechanical thrombectomy for early treatment of massive pulmonary embolism. Author(s): Reekers JA, Baarslag HJ, Koolen MG, Van Delden O, van Beek EJ. Source: Cardiovascular and Interventional Radiology. 2003 May-June; 26(3): 246-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14562972

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Metachronous Wilms tumor associated with pulmonary embolism: how can we detect these cases early? A case report and literature review. Author(s): Ahmed R, al-Salti W, Raafat F, Morland B. Source: Pediatric Hematology and Oncology. 2003 January-February; 20(1): 55-63. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12687754

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Methodology for a rapid protocol to rule out pulmonary embolism in the emergency department. Author(s): Kline JA, Wells PS. Source: Annals of Emergency Medicine. 2003 August; 42(2): 266-75. Review. Erratum In: Ann Emerg Med. 2003 October; 42(4): 600. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12883516

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Misdiagnosis of pulmonary embolism in patients with allergic reaction--the importance of prior probability of disease. Author(s): Janata K, Prokop M, Schaefer-Prokop C, Laggner AN. Source: Wiener Klinische Wochenschrift. 2003 October 31; 115(19-20): 728-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14650950

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Modulation and roles of the endothelins in the pathophysiology of pulmonary embolism. Author(s): Battistini B. Source: Canadian Journal of Physiology and Pharmacology. 2003 June; 81(6): 555-69. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12839267

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Mortality and pulmonary embolism after fracture in the elderly. Author(s): Barrett JA, Baron JA, Beach ML. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2003 November; 14(11): 889-94. Epub 2003 August 26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12942231

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Mortality of patients with pulmonary embolism. Author(s): Janata K, Holzer M, Domanovits H, Mullner M, Bankier A, Kurtaran A, Bankl HC, Laggner AN. Source: Wiener Klinische Wochenschrift. 2002 September 30; 114(17-18): 766-72. Erratum In: Wien Klin Wochenschr. 2002 December 19; 114(23-24): 1026. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12416281

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MRI for the diagnosis of pulmonary embolism. Author(s): van Beek EJ, Wild JM, Fink C, Moody AR, Kauczor HU, Oudkerk M. Source: Journal of Magnetic Resonance Imaging : Jmri. 2003 December; 18(6): 627-40. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14635147

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Multidetector-row CT imaging of pulmonary embolism. Author(s): Schoepf UJ, Costello P. Source: Semin Roentgenol. 2003 April; 38(2): 106-14. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12854435

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Multifocal right atrial myxoma and pulmonary embolism. Author(s): Parsons AM, Detterbeck FC. Source: The Annals of Thoracic Surgery. 2003 April; 75(4): 1323-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12683591

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N-butyl-2-cyanoacrylate pulmonary embolism after endoscopic injection sclerotherapy for gastric variceal bleeding. Author(s): Hwang SS, Kim HH, Park SH, Kim SE, Jung JI, Ahn BY, Kim SH, Chung SK, Park YH, Choi KH. Source: Journal of Computer Assisted Tomography. 2001 January-February; 25(1): 16-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11176287

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Near-fatal pulmonary embolism. Author(s): DePalo LR. Source: The Mount Sinai Journal of Medicine, New York. 2001 November; 68(6): 370-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11687864

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Negative findings on helical CT in suspected pulmonary embolism. Author(s): Larcos G. Source: Ajr. American Journal of Roentgenology. 2000 March; 174(3): 871-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10701646

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Negative spiral CT in acute pulmonary embolism. Author(s): Nilsson T, Olausson A, Johnsson H, Nyman U, Aspelin P. Source: Acta Radiologica (Stockholm, Sweden : 1987). 2002 September; 43(5): 486-91. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12423459

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New CT index to quantify arterial obstruction in pulmonary embolism: comparison with angiographic index and echocardiography. Author(s): Qanadli SD, El Hajjam M, Vieillard-Baron A, Joseph T, Mesurolle B, Oliva VL, Barre O, Bruckert F, Dubourg O, Lacombe P. Source: Ajr. American Journal of Roentgenology. 2001 June; 176(6): 1415-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11373204

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New methods for estimating pretest probability in the diagnosis of pulmonary embolism. Author(s): Ghali WA, Cornuz J, Perrier A. Source: Current Opinion in Pulmonary Medicine. 2001 September; 7(5): 349-53. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11584188

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Newer diagnostic modalities for pulmonary embolism. Pulmonary angiography using CT and MR imaging compared with conventional angiography. Author(s): Bloomgarden DC, Rosen MP. Source: Emergency Medicine Clinics of North America. 2001 November; 19(4): 975-94. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11762283

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Non-invasive exclusion and diagnosis of pulmonary embolism by sequential use of the rapid ELISA D-dimer assay, clinical score and spiral CT. Author(s): Michiels JJ, Schroyens W, De Backer W, van der Planken M, Hoogsteden H, Pattynama PM. Source: International Angiology : a Journal of the International Union of Angiology. 2003 March; 22(1): 1-14. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12771850

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Non-invasive tests for acute pulmonary embolism: what are the real advances? Author(s): Lim TK. Source: Singapore Med J. 2001 October; 42(10): 446-9. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11874146

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Noninvasive venous testing in the diagnosis of pulmonary embolism: the impact on decisionmaking. Author(s): Lipski DA, Shepard AD, McCarthy BD, Ernst CB. Source: Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. 1997 November; 26(5): 757-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9372812

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Nonspecific tests for pulmonary embolism. Author(s): Weiner SG, Burstein JL. Source: Emergency Medicine Clinics of North America. 2001 November; 19(4): 943-55. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11762281

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Non-traumatic thoracic emergencies: CT diagnosis of acute pulmonary embolism: the first 10 years. Author(s): Ghaye B, Remy J, Remy-Jardin M. Source: European Radiology. 2002 August; 12(8): 1886-905. Epub 2002 June 08. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12136308

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Non-traumatic thoracic emergencies: CT venography in an integrated diagnostic strategy of acute pulmonary embolism and venous thrombosis. Author(s): Ghaye B, Dondelinger RF. Source: European Radiology. 2002 August; 12(8): 1906-21. Epub 2002 June 21. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12136309

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Normal D-dimer levels in emergency department patients suspected of acute pulmonary embolism. Author(s): Dunn KL, Wolf JP, Dorfman DM, Fitzpatrick P, Baker JL, Goldhaber SZ. Source: Journal of the American College of Cardiology. 2002 October 16; 40(8): 1475-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12392839

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Normal perfusion scintigraphy in pulmonary embolism. Causes and diagnostic alternatives. Author(s): Hartmann IJ, Wust AF, Melissant CF, Stokkel MP. Source: The Netherlands Journal of Medicine. 2000 October; 57(4): 157-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11006492

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Normoxemia and pulmonary embolism. Author(s): Egermayer P. Source: Chest. 2001 November; 120(5): 1756. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11713177

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Novel management strategy for patients with suspected pulmonary embolism. Author(s): Kucher N, Luder CM, Dornhofer T, Windecker S, Meier B, Hess OM. Source: European Heart Journal. 2003 February; 24(4): 366-76. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12581684

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N-terminal pro-brain natriuretic peptide in patients with acute pulmonary embolism. Author(s): Pruszczyk P, Kostrubiec M, Bochowicz A, Styczynski G, Szulc M, Kurzyna M, Fijalkowska A, Kuch-Wocial A, Chlewicka I, Torbicki A. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2003 October; 22(4): 649-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14582919

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Obesity, oral contraceptives, and fatal pulmonary embolism. Author(s): Egermayer P. Source: N Z Med J. 2001 April 13; 114(1129): 170-1. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11400927

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Occult colon cancer in a patient with an unexplained episode of pulmonary embolism. Author(s): Caputo F, Musardo G, Savini P, Balducci G, Marchi G, Corbelli C, Bernardi M, Addolorato G, Stefanini GF. Source: Hepatogastroenterology. 2000 January-February; 47(31): 165-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10690603

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Operating characteristics of automated latex immunoassay fibrin D-dimer tests in the diagnosis of angiographically-defined acute pulmonary embolism. Author(s): Heit JA, Meyers BJ, Plumhoff EA, Larson DR, Nichols WL. Source: Thrombosis and Haemostasis. 2000 June; 83(6): 970. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10896262

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Optimal scan delay in spiral CT for the diagnosis of acute pulmonary embolism. Author(s): Hartmann IJ, Lo RT, Bakker J, de Monye W, van Waes PF, Pattynama PM. Source: Journal of Computer Assisted Tomography. 2002 January-February; 26(1): 21-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11801900

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Optional therapeutic strategies based on clinically different types of acute pulmonary embolism. Author(s): Wang L, Wei L, Liu Y, Li X, Guo X, Zhi J, Ai Y. Source: Chinese Medical Journal. 2003 June; 116(6): 849-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12877793

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Oral contraceptives and fatal pulmonary embolism. Author(s): Parkin L, Skegg DC, Wilson M, Herbison GP, Paul C. Source: Lancet. 2000 June 17; 355(9221): 2133-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10902629

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Outcomes after withholding anticoagulation from patients with suspected acute pulmonary embolism and negative computed tomographic findings: a cohort study. Author(s): Swensen SJ, Sheedy PF 2nd, Ryu JH, Pickett DD, Schleck CD, Ilstrup DM, Heit JA. Source: Mayo Clinic Proceedings. 2002 February; 77(2): 130-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11838646

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Outpatient treatment of patients with deep-vein thrombosis or pulmonary embolism. Author(s): Wells PS. Source: Current Opinion in Pulmonary Medicine. 2001 September; 7(5): 360-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11584190

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Outpatient treatment of pulmonary embolism is feasible and safe in a substantial proportion of patients. Author(s): Beer JH, Burger M, Gretener S, Bernard-Bagattini S, Bounameaux H. Source: Journal of Thrombosis and Haemostasis : Jth. 2003 January; 1(1): 186-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12871557

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Overview of Prospective Investigation of Pulmonary Embolism Diagnosis II. Author(s): Gottschalk A, Stein PD, Goodman LR, Sostman HD. Source: Semin Nucl Med. 2002 July; 32(3): 173-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12105798

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Perioperative pulmonary embolism. Author(s): Rosenberger P, Shernan SK, Eltzschig HK. Source: Anesthesia and Analgesia. 2003 December; 97(6): 1855. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14633578

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Prevalence of increased cardiac troponin I levels in patients with and without acute pulmonary embolism and relation of increased cardiac troponin I levels with inhospital mortality in patients with acute pulmonary embolism. Author(s): Yalamanchili K, Sukhija R, Aronow WS, Sinha N, Fleisher AG, Lehrman SG. Source: The American Journal of Cardiology. 2004 January 15; 93(2): 263-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14715366

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Pulmonary embolism after lung resection: diagnosis and treatment. Author(s): Kameyama K, Huang CL, Liu D, Okamoto T, Hayashi E, Yamamoto Y, Yokomise H. Source: The Annals of Thoracic Surgery. 2003 August; 76(2): 599-601. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12902112

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Pulmonary embolism and thrombotic thrombocytopenic purpura in acute promyelocytic leukemia treated with all-trans retinoic acid. Author(s): Fujita H, Takemura S, Hyo R, Tanaka M, Koharazawa H, Fujisawa S, Kanamori H, Ishigatsubo Y. Source: Leukemia & Lymphoma. 2003 September; 44(9): 1627-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14565670

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Pulmonary embolism associated with intravenous immunoglobulin therapy. Author(s): Butler KS, Zeitlin DS. Source: The Annals of Pharmacotherapy. 2003 October; 37(10): 1530. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14519037

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Pulmonary embolism in pernicious anemia and hyperhomocysteinemia. Author(s): Andres E, Kurtz JE. Source: Chest. 2003 September; 124(3): 1181. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12970061

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Pulmonary embolism in pregnant patients: a survey of practices and policies for CT pulmonary angiography. Author(s): Schuster ME, Fishman JE, Copeland JF, Hatabu H, Boiselle PM. Source: Ajr. American Journal of Roentgenology. 2003 December; 181(6): 1495-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14627562

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Pulmonary embolism mortality in the United States, 1979-1998: an analysis using multiple-cause mortality data. Author(s): Horlander KT, Mannino DM, Leeper KV. Source: Archives of Internal Medicine. 2003 July 28; 163(14): 1711-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12885687

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Pulmonary embolism. Author(s): Wolfe WG. Source: Annals of Surgery. 2003 December; 238(6 Suppl): S67-71. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14703747

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Pulmonary embolism: an overview. Author(s): Ramachandran P, Oomman A. Source: J Indian Med Assoc. 2003 April; 101(4): 248-9, 265. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12964642

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QR in V1--an ECG sign associated with right ventricular strain and adverse clinical outcome in pulmonary embolism. Author(s): Kucher N, Walpoth N, Wustmann K, Noveanu M, Gertsch M. Source: European Heart Journal. 2003 June; 24(12): 1113-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12804925

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Quality improvement guidelines for percutaneous permanent inferior vena cava filter placement for the prevention of pulmonary embolism. SCVIR Standards of Practice Committee. Author(s): Grassi CJ, Swan TL, Cardella JF, Meranze SG, Oglevie SB, Omary RA, Roberts AC, Sacks D, Silverstein MI, Towbin RB, Lewis CA; Society of Cardiovascular & Interventional Radiology, Standards of Practice Committee. Source: Journal of Vascular and Interventional Radiology : Jvir. 2001 February; 12(2): 137-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11265876

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Radiation dose in helical CT for detection of pulmonary embolism. Author(s): Diederich S. Source: European Radiology. 2003 July; 13(7): 1491-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12899129

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Right heart thrombi in pulmonary embolism: results from the International Cooperative Pulmonary Embolism Registry. Author(s): Torbicki A, Galie N, Covezzoli A, Rossi E, De Rosa M, Goldhaber SZ; ICOPER Study Group. Source: Journal of the American College of Cardiology. 2003 June 18; 41(12): 2245-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12821255

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Right ventricular damage due to pulmonary embolism: examination of the number of infiltrating macrophages. Author(s): Iwadate K, Doi M, Tanno K, Katsumura S, Ito H, Sato K, Yonemura I, Ito Y. Source: Forensic Science International. 2003 July 8; 134(2-3): 147-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12850410

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Right-sided chest-lead abnormalities on EKG in acute pulmonary embolism. Author(s): Cheng TO. Source: Journal of the National Medical Association. 2003 September; 95(9): 862. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14527054

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Right-sided chest-lead abnormalities on EKG in acute pulmonary embolism: ST elevation. Author(s): Diaz M, Vidal A. Source: Journal of the National Medical Association. 2004 January; 96(1): 126. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14746362

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Right-sided EKG in pulmonary embolism. Author(s): Akula R, Hasan SP, Alhassen M, Mujahid H, Amegashie E. Source: Journal of the National Medical Association. 2003 August; 95(8): 714-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12934868

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Risk factors for clinically relevant pulmonary embolism and deep venous thrombosis in patients undergoing primary hip or knee arthroplasty. Author(s): Mantilla CB, Horlocker TT, Schroeder DR, Berry DJ, Brown DL. Source: Anesthesiology. 2003 September; 99(3): 552-60; Discussion 5A. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12960538

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Risk of clinical pulmonary embolism after joint surgery in patients receiving lowmolecular-weight heparin prophylaxis in hospital: a 10-year prospective register of 3,954 patients. Author(s): Dahl OE, Gudmundsen TE, Bjornara BT, Solheim DM. Source: Acta Orthopaedica Scandinavica. 2003 June; 74(3): 299-304. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12899550

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Risk of pulmonary embolism after negative MDCT pulmonary angiography findings. Author(s): Kavanagh EC, O'Hare A, Hargaden G, Murray JG. Source: Ajr. American Journal of Roentgenology. 2004 February; 182(2): 499-504. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14736689

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Ruptured ascending aorta aneurysm presenting as pulmonary embolism. Author(s): Choukroun EM, Braganca C, Madonna FP, Deville C. Source: European Journal of Cardio-Thoracic Surgery : Official Journal of the European Association for Cardio-Thoracic Surgery. 2003 August; 24(2): 299. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12895624

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Scintigraphic probability and angiographic diagnostic certainty in acute pulmonary embolism. Author(s): Lette J, Cerino M, Barrette G, Dufresne MP, De Maria S, Eybalin MC, Levasseur A. Source: Clinical Nuclear Medicine. 2003 November; 28(11): 897-904. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14578704

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Sensitivity and specificity of the semiquantitative latex agglutination D-dimer assay for the diagnosis of acute pulmonary embolism as defined by computed tomographic angiography. Author(s): Froehling DA, Elkin PL, Swensen SJ, Heit JA, Pankratz VS, Ryu JH. Source: Mayo Clinic Proceedings. 2004 February; 79(2): 164-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14959909

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Subcutaneous fondaparinux versus intravenous unfractionated heparin in the initial treatment of pulmonary embolism. Author(s): Buller HR, Davidson BL, Decousus H, Gallus A, Gent M, Piovella F, Prins MH, Raskob G, van den Berg-Segers AE, Cariou R, Leeuwenkamp O, Lensing AW; Matisse Investigators. Source: The New England Journal of Medicine. 2003 October 30; 349(18): 1695-702. Erratum In: N Engl J Med. 2004 January 22; 350(4): 423. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14585937

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Successful management of acute pulmonary embolism after surgery for lung cancer. Author(s): Sakuragi T, Sakao Y, Furukawa K, Rikitake K, Ohtsubo S, Okazaki Y, Natsuaki M, Itoh T. Source: European Journal of Cardio-Thoracic Surgery : Official Journal of the European Association for Cardio-Thoracic Surgery. 2003 October; 24(4): 580-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14500078

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Successful resuscitation of a patient with acute massive pulmonary embolism using emergent embolectomy. Author(s): Georghiou GP, Brauner R, Berman M, Stamler A, Glanz L, Vidne BA, Erez E. Source: The Annals of Thoracic Surgery. 2004 February; 77(2): 697-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14759464

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Successful thrombolysis of submassive pulmonary embolism after bariatric surgery: expanding the indications and addressing the controversies. Author(s): Pulipati RC, Lazzaro RS, Macura J, Savel RH. Source: Obesity Surgery : the Official Journal of the American Society for Bariatric Surgery and of the Obesity Surgery Society of Australia and New Zealand. 2003 October; 13(5): 792-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14627480

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Successful treatment of massive pulmonary embolism in the 38th week of pregnancy. Author(s): Funakoshi Y, Kato M, Kuratani T, Shigemura N, Kaneko M. Source: The Annals of Thoracic Surgery. 2004 February; 77(2): 694-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14759462

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Superficial femoral vein aneurysm with massive pulmonary embolism. Author(s): Pandey V, Wolfe JH. Source: Journal of the Royal Society of Medicine. 2003 September; 96(9): 460-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12949206

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Suspected pulmonary embolism: evidence-based diagnostic testing. Author(s): Ebell MH. Source: American Family Physician. 2004 February 1; 69(3): 599-601. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14971843

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Suspected pulmonary embolism: part I. Evidence-based clinical assessment. Author(s): Ebell MH. Source: American Family Physician. 2004 January 15; 69(2): 367-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14765779

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The case for thrombolysis in acute major pulmonary embolism: hemodynamic benefits and beyond. Author(s): Konstantinides S. Source: Intensive Care Medicine. 2002 November; 28(11): 1547-51. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12583373

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The effect of helical computed tomography on diagnostic and treatment strategies in patients with suspected pulmonary embolism. Author(s): Trowbridge RL, Araoz PA, Gotway MB, Bailey RA, Auerbach AD. Source: The American Journal of Medicine. 2004 January 15; 116(2): 84-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14715321

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The late outcomes of vena cava filters in the prevention of pulmonary embolism. Author(s): Kurtoglu M, Guloglu R, Alimoglu O, Necefli A, Poyanli A. Source: Ulus Travma Derg. 2003 April; 9(2): 114-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12836107

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The presence of shock defines the threshold to initiate thrombolytic therapy in patients with pulmonary embolism. Author(s): Wood KE. Source: Intensive Care Medicine. 2002 November; 28(11): 1537-46. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12583371

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Thrombolysis in the treatment of submassive pulmonary embolism. Author(s): Mascitelli L, Pezzetta F. Source: Archives of Internal Medicine. 2003 May 26; 163(10): 1238; Author Reply 1238. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12767964

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Tissue plasminogen activator plasma levels as a potential diagnostic aid in acute pulmonary embolism. Author(s): Flores J, Garcia-Avello A, Flores VM, Navarro JL, Canseco F, PerezRodriguez E. Source: Archives of Pathology & Laboratory Medicine. 2003 March; 127(3): 310-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12653574

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Tracheomalacia incidentally detected on CT pulmonary angiography of patients with suspected pulmonary embolism. Author(s): Hasegawa I, Boiselle PM, Raptopoulos V, Hatabu H. Source: Ajr. American Journal of Roentgenology. 2003 December; 181(6): 1505-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14627565

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Tracking the uptake of evidence: two decades of hospital practice trends for diagnosing deep vein thrombosis and pulmonary embolism. Author(s): Stein PD, Hull RD, Ghali WA, Patel KC, Olson RE, Meyers FA, Kalra NK. Source: Archives of Internal Medicine. 2003 May 26; 163(10): 1213-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12767959

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Troponin levels as a guide to treatment of pulmonary embolism. Author(s): Horlander KT, Leeper KV. Source: Current Opinion in Pulmonary Medicine. 2003 September; 9(5): 374-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12904706

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Turbidimetric D-dimer test in the diagnosis of pulmonary embolism: a metaanalysis. Author(s): Brown MD, Lau J, Nelson RD, Kline JA. Source: Clinical Chemistry. 2003 November; 49(11): 1846-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14578316

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Under-representation of the -455A beta-fibrinogen allele in survivors of pulmonary embolism. Author(s): Kapustin SI, Blinov MN, Papayan LP, Imyanitov EN, Mitchell MJ, Savidge GF. Source: Thrombosis Research. 2002 April 1; 106(1): 89-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12165294

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Unusual echocardiographic presentations of pulmonary embolism in transit. Author(s): Leitman M, Sidenko S, Peleg E, Wolf R, Sucher E, Rosenblath S, Vered Z. Source: Isr Med Assoc J. 2003 September; 5(9): 675-6. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14509165

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Unusual presentation of mucoepidermoid carcinoma with recurrent pulmonary embolism. Author(s): Devbhandari M, Stamenkovic S, Walker W, Cameron E. Source: European Journal of Cardio-Thoracic Surgery : Official Journal of the European Association for Cardio-Thoracic Surgery. 2002 September; 22(3): 482-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12204754

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Use of natriuretic peptides in guiding treatment decisions for acute pulmonary embolism. Author(s): Smithline H. Source: Circulation. 2003 September 30; 108(13): E93; Author Reply E93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14517155

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Use of pulse oximetry to predict in-hospital complications in normotensive patients with pulmonary embolism. Author(s): Kline JA, Hernandez-Nino J, Newgard CD, Cowles DN, Jackson RE, Courtney DM. Source: The American Journal of Medicine. 2003 August 15; 115(3): 203-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12935827

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Use of rheolytic thrombectomy in treatment of acute massive pulmonary embolism. Author(s): Zeni PT Jr, Blank BG, Peeler DW. Source: Journal of Vascular and Interventional Radiology : Jvir. 2003 December; 14(12): 1511-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14654484

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Use of the abdominal wall fat index determined ultrasonographically for assessing the risk of post-operative pulmonary embolism. Author(s): Nishikawa N, Kurabayashi T, Tomita M, Matsushita H, Aoki Y, Tanaka K. Source: International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics. 2000 March; 68(3): 241-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10699195

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Use of thrombolytic therapy to treat heparin-refractory pulmonary embolism in a menstruating patient. Author(s): Koch AZ, Abubaker J, Barnett VT, Chan LN. Source: Pharmacotherapy. 2002 January; 22(1): 118-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11794423

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Utility of brain natriuretic peptide to predict right ventricular dysfunction and clinical outcome in patients with acute pulmonary embolism. Author(s): Thabut G, Logeart D. Source: Circulation. 2003 September 30; 108(13): E94; Author Reply E94-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14631970

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Utility of brain natriuretic peptide to predict right ventricular dysfunction and clinical outcome in patients with acute pulmonary embolism. Author(s): Kruger S, Merx MW, Graf J. Source: Circulation. 2003 September 30; 108(13): E94; Author Reply E94-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14517156

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V/Q-scanning/SPECT for the diagnosis of pulmonary embolism. Author(s): Schumichen C. Source: Respiration; International Review of Thoracic Diseases. 2003 July-August; 70(4): 329-42. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14512664

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Validity of D-dimer tests for pulmonary embolism: better to diagnose or exclude? Author(s): Caine GJ, Lip GY. Source: Annals of Emergency Medicine. 2003 May; 41(5): 756; Author Reply 756-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12744250

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Validity of index of suspicion for pulmonary embolism after hip arthroplasty. Author(s): Lawton RL, Morrey BF, Narr BJ. Source: Clinical Orthopaedics and Related Research. 2003 October; (415): 180-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14612645

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Value of chest X-ray combined with perfusion scan versus ventilation/perfusion scan in acute pulmonary embolism. Author(s): de Groot MR, Turkstra F, van Marwijk Kooy M, Oostdijk AH, van Beek EJ, Buller HR. Source: Thrombosis and Haemostasis. 2000 March; 83(3): 412-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10744146

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Value of structured clinical and scintigraphic protocols in acute pulmonary embolism. Author(s): Nilsson T, Mare K, Carlsson A. Source: Journal of Internal Medicine. 2001 September; 250(3): 213-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11555125

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Value of transthoracic echocardiography in the diagnosis of pulmonary embolism: results of a prospective study in unselected patients. Author(s): Miniati M, Monti S, Pratali L, Di Ricco G, Marini C, Formichi B, Prediletto R, Michelassi C, Di Lorenzo M, Tonelli L, Pistolesi M. Source: The American Journal of Medicine. 2001 May; 110(7): 528-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11343666

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Variable diagnostic approach to suspected pulmonary embolism in the ED of a major academic tertiary care center. Author(s): Prologo JD, Glauser J. Source: The American Journal of Emergency Medicine. 2002 January; 20(1): 5-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11781903

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Variation in medical resource utilisation in the management of pulmonary embolism in Belgium. Author(s): Annemans L, Robays H, Bruart J, Verstraeten P. Source: Acta Clin Belg. 2002 January-February; 57(1): 11-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12017750

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Ventilation/perfusion scan and dead space in pulmonary embolism: are they useful for the diagnosis? Author(s): Giuntini C. Source: Q J Nucl Med. 2001 December; 45(4): 281-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11893964

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Ventilation-perfusion-chest radiography match is less likely to represent pulmonary embolism if perfusion is decreased rather than absent. Author(s): Kim CK, Worsley DF, Alavi A. Source: Clinical Nuclear Medicine. 2000 September; 25(9): 665-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10983750

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Westermark sign and suspected pulmonary embolism. Author(s): Ray JG. Source: The Canadian Journal of Cardiology. 2003 March 15; 19(3): 317; Author Reply 317. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12680403

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What are the most reliable detection methods for deep vein thrombosis and pulmonary embolism to be used as endpoints in trials of venous thromboprophylaxis? Author(s): Davidson BL. Source: Haemostasis. 1998; 28 Suppl 3: 113-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10069772

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•

When atrial fibrillation occurs with pulmonary embolism, is it the chicken or the egg? Author(s): Flegel KM. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 1999 April 20; 160(8): 1181-2. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10234351

•

Whole blood D-dimer assay: an effective noninvasive method to rule out pulmonary embolism. Author(s): Owings JT, Gosselin RC, Battistella FD, Anderson JT, Petrich M, Larkin EC. Source: The Journal of Trauma. 2000 May; 48(5): 795-9; Discussion 799-800. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10823521

•

Wilms' tumour presenting as a pulmonary embolism. Author(s): Ceelen W, Kerremans I, Lutz-Dettinger N, Vandenbroeck P, de Hemptinne B. Source: Acta Chir Belg. 1997 June; 97(3): 148-50. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9224522

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CHAPTER 2. NUTRITION AND PULMONARY EMBOLISM Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and pulmonary embolism.

Finding Nutrition Studies on Pulmonary Embolism 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 “pulmonary embolism” (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 “pulmonary embolism” (or a synonym): •

A comparison of radiopharmaceutical agents used for the diagnosis of pulmonary embolism. Author(s): Department of Pharmacy, Lariboisiere Hospital, Paris, France. [email protected] Source: Rizzo Padoin, N Farina, A Le Pen, C Duet, M Mundler, O Leverge, R Nucl-MedCommun. 2001 April; 22(4): 375-81 0143-3636

•

A nonclassic case of pulmonary embolism. Author(s): University of California, School of Medicine, San Francisco. Source: Rapaport, E Hosp-Pract-(Off-Ed). 1992 September 15; 27(9): 86-9, 93, 96 passim; discussion 101 8750-2836

•

Active implementation of a consensus strategy improves diagnosis and management in suspected pulmonary embolism. Author(s): Zuiderziekenhuis, Rotterdam, University Hospital Rotterdam, Rotterdam, The Netherlands. Source: Berghout, A Oudkerk, M Hicks, S G Teng, T H Pillay, M Buller, H R QJM. 2000 June; 93(6): 335-40 1460-2725

•

Compliance with guidelines for the investigation and management of patients with suspected pulmonary embolism at Christchurch Hospital. Author(s): Department of Medicine, Christchurch School of Medicine. Source: Egermayer, P Town, G I N-Z-Med-J. 1998 March 13; 111(1061): 70-3 0028-8446

•

Deep venous thrombosis and pulmonary emboli: etiology, medical treatment, and prophylaxis. Author(s): Evans Memorial Department of Clinical Research, University Hospital, Boston University Medical Center, Massachusetts. Source: Coffman, J D J-Thorac-Imaging. 1989 October; 4(4): 4-7 0883-5993

•

MDL 72222 (a selective 5-HT3 receptor antagonist) prevents stimulation of intrapulmonary C fibres by pulmonary embolization in anaesthetized rabbits. Author(s): School of Health Sciences, Liverpool Polytechnic. Source: Kay, I S Armstrong, D J Exp-Physiol. 1991 March; 76(2): 213-8 0958-0670

•

MRA of the lower extremities in patients with pulmonary embolism using a blood pool contrast agent: initial experience. Author(s): Department of Radiology and Ludwig- Boltzmann-Institute for Clinical and Experimental Radiological Research, General Hospital and University of Vienna Austria. [email protected] Source: Hoffmann, Udo Loewe, Christian Bernhard, Christoph Weber, Michael Cejna, Manfred Herold, Christian J Schima, Wolfgang J-Magn-Reson-Imaging. 2002 April; 15(4): 429-37 1053-1807

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Pulmonary embolism due to right ventricular thrombus in a case of Behcet's disease. Author(s): First Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan. Source: Yasuo, M Nagano, S Yazaki, Y Koizumi, T Kitabayashi, H Imamura, H Amano, J Isobe, M Jpn-Circ-J. 1999 November; 63(11): 909-11 0047-1828

•

Pulmonary embolism following anticoagulation therapy. Author(s): National Spinal Injuries Centre, Stoke Mandeville Hospital. Source: Silver, J R Noori, Z Int-Disabil-Stud. 1991 Jan-March; 13(1): 16-9 0259-9147

Nutrition 73

•

Pulmonary embolism update. Lessons for the '90s. Author(s): Department of Respiratory Care, William Beaumont Hospital, Royal Oak, Michigan. Source: Sherman, S Postgrad-Med. 1991 June; 89(8): 195-9, 202 0032-5481

•

Pulmonary embolism. Incidence in primary cemented and uncemented total hip arthroplasty using low-dose sodium warfarin prophylaxis. Author(s): Department of Orthopaedic Surgery, Thomas Jefferson University, Rothman Institute, Philadelphia, Pennsylvania 19107. Source: Wolf, L R Hozack, W J Balderston, R A Booth, R E Rothman, R H J-Arthroplasty. 1992 December; 7(4): 465-70 0883-5403

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Pulmonary embolization of a pacing electrode fragment complicating lead extraction. Author(s): Department of Cardiology, East Yorkshire NHS Trust, Hull, United Kingdom. Source: Walters, M I Kaye, G C Pacing-Clin-Electrophysiol. 1999 May; 22(5): 823-4 01478389

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Pulmonary thromboembolism after spinal instrumentation surgery. Author(s): Department of Orthopedic Surgery, Juntendo University Urayasu Hospital, 2-1-1 Tomioka, Urayasu, Chiba 279-0021, Japan. Source: Arai, Y Shitoto, K Muta, T Kurosawa, H J-Orthop-Sci. 1999; 4(5): 380-3 0949-2658

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Scintigraphic detection of pulmonary embolization of esophageal variceal sclerosant. Author(s): Department of Radiology, Emory University School of Medicine, Atlanta, GA. Source: DePuey, E G Richards, W O Millikan, W J Henderson, J M Endoscopy. 1988 May; 20(3): 91-4 0013-726X

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Spiral CT angiography for suspected pulmonary embolism: a cost-effectiveness analysis. Author(s): Department of Radiology, Beth Israel Deaconess Hospital, Boston, Mass., USA. Source: Rosen, M P Acad-Radiol. 1999 January; 6(1): 72-4; discussion 74-5 1076-6332

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The prevention of pulmonary embolism in total hip arthroplasty. Evaluation of lowdose warfarin therapy. Author(s): Thomas Jefferson University, Philadelphia, Pennsylvania. Source: Balderston, R A Graham, T S Booth, R E Rothman, R H J-Arthroplasty. 1989 September; 4(3): 217-21 0883-5403

•

Two strategies for prophylaxis of fatal postoperative pulmonary embolism. Costeffectiveness analysis. Author(s): University of Minnesota. Source: Hillson, S D Rich, E C Int-J-Technol-Assess-Health-Care. 1990; 6(3): 470-9 02664623

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Venous thrombosis and pulmonary embolism. Author(s): New York University School of Medicine. Source: Wessler, S Hosp-Pract-(Off-Ed). 1987 December 15; 22(12): 159-72, 177-8, 181 8750-2836

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Warfarin prophylaxis to prevent mortality from pulmonary embolism after total hip replacement. Author(s): Division of Orthopaedic Surgery, Center for the Health Sciences, University of California, Los Angeles School of Medicine 90024-1749.

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Source: Amstutz, H C Friscia, D A Dorey, F Carney, B T J-Bone-Joint-Surg-Am. 1989 March; 71(3): 321-6 0021-9355

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

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

•

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

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

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

•

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/

•

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/

•

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

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

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

•

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

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

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

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

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

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

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

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CHAPTER 3. EMBOLISM

CLINICAL

TRIALS

AND

PULMONARY

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

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

A safety and efficacy trial evaluating the use of SanOrg34006 compared to placebo in patients who have completed 6 months of treatment for symptomatic pulmonary embolism or deep vein thrombosis Condition(s): Pulmonary Embolism; Deep Vein Thrombosis Study Status: This study is currently recruiting patients. Sponsor(s): Organon Purpose - Excerpt: Patients diagnosed with pulmonary embolism (blood clot in the lung) or deep vein thrombosis (blood clot in a leg vein) are at risk for these blood clots to reoccur. Anticoagulant (blood-thinning) drugs are normally given immediately after the clot is discovered and are continued for a period of 3 or 6 months during which time the risk for recurrence is highest. Research has shown that when oral anticoagulants are used appropriately during this period, patients are less at risk for a recurrent blood clot and this risk reduction outweighs the potential for bleeding to occur. In this study, patients who had a blood clot in the lung or in a leg vein and completed 6 months of treatment with daily oral vitamin K antagonists (acenocoumarol or warfarin) or onceweekly injections of SanOrg34006 (a new anticoagulant drug) will receive an additional 6 months of once-weekly SanOrg34006 injections or injections of a solution containing no drug (placebo). This trial will evaluate whether patients treated for an additional 6 months with SanOrg34006 have fewer recurrences of blood clots when compared to patients treated with placebo. Assignment to either SanOrg34006 or placebo will be

8

These are listed at www.ClinicalTrials.gov.

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purely by chance. Neither the patients nor their doctors will know which treatment is being given. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00071279 •

A safety and efficacy trial evaluating the use of SanOrg34006 in the treatment of pulmonary embolism Condition(s): Pulmonary Embolism Study Status: This study is currently recruiting patients. Sponsor(s): Organon Purpose - Excerpt: Patients who have a pulmonary embolism (blood clot in the lung) will be treated in this study. The purpose of the study is to compare the safety and effectiveness of a new injectable anticoagulant (blood-thinning) drug, SanOrg34006, with the standard way of treating a pulmonary embolism. The standard treatment includes injections or infusions of an anticoagulant drug, (LMW)heparin, for about a week followed by anticoagulant tablets (warfarin or acenocoumarol) which are taken by mouth. Assignment to either SanOrg34006 or (LMW)heparin plus warfarin or acenocoumarol will be purely by chance and will be known by both patients and their doctors. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00062803

•

Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED II) Condition(s): Lung Diseases; Pulmonary Embolism; Venous Thromboembolism Study Status: This study is currently recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To determine the value of contrast enhanced spiral computed tomography (spiral CT) for the diagnosis of acute pulmonary embolism (PE). Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00007085

•

Risk Factors for Venous Thromboembolism Condition(s): Deep Venous Thrombosis; Pulmonary Embolism Study Status: This study is currently recruiting patients. Sponsor(s): Department of Veterans Affairs Medical Research Service Purpose - Excerpt: Deep venous thrombosis is the presence of blood clots, usually in the legs that lead to either local problems or breathing problems if the clot moves to the lungs. This study is designed to assess both clinical conditions as well as common

Clinical Trials 77

genetic factors that lead to more risk of deep venous thrombosis. Clinical conditions of venous thrombosis include: stroke, malignancy, and situations such as surgery, pregnancy, trauma, or travel. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00018772

Keeping Current on Clinical Trials The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to the Web site at http://www.clinicaltrials.gov/ and search by “pulmonary embolism” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: •

For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/

•

For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html

•

For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/

•

For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm

•

For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm

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For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm

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For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp

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For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm

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For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/

•

For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm

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•

For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm

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For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm

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For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm

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For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm

•

For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials

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CHAPTER 4. PATENTS ON PULMONARY EMBOLISM Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.9 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “pulmonary embolism” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on pulmonary embolism, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Pulmonary Embolism By performing a patent search focusing on pulmonary embolism, 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. 9Adapted

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 pulmonary embolism: •

Anti-Pulmonary embolism filter Inventor(s): Dibie; Alain (Paris, FR), Musset; Dominique (Rueil, FR) Assignee(s): Association Pour LA Recherche EN Imagerie DE L'hopital Antoine Beclere (clamart, Fr), Foundation Pour L'avenir Pour LA Recherche Medicale Appliquee (paris, Fr) Patent Number: 5,531,788 Date filed: May 2, 1994 Abstract: The present invention relates to an anti-pulmonary embolism filter of the pe made of a remanent spring effect resilient wire, characterized in that it is shaped into a spiral (1) having three non-touching turns (2, 3, 4) with the middle turn (3) having a diameter (d3) greater than the diameters (d2, d4) of the other two turns, and in that this diameter (d3) is selected to be close to the half-circumference of the vena cava in the zone where the filter is to be implanted so as to ensure that the function of holding the filter in place by flattening of the vena cava is optimized. Excerpt(s): The present invention relates to an anti-pulmonary embolism filter and to a kit for presenting and installing the filter. Various types of filter are already known and are actually in use for the purpose of being installed in the inferior vena cava in order to prevent clots migrating to the right heart from the veins of the lower limbs or of the true pelvis. Particular mention may be made of the filters known under the names of: MobinUddin, Greenfield, Gunther, and L.G. Medical. Web site: http://www.delphion.com/details?pn=US05531788__

•

Anti-pulmonary embolism filter and corresponding presentation and fitting kit Inventor(s): Catteau; Gilles (Auneau Cedex, FR), Dibie; Alain (Paris, FR), Musset; Dominique (Clamart, FR), Prou; Philippe (Auneau Cedex, FR) Assignee(s): Ethnor (neuilly-sur-seine Cedex, Fr) Patent Number: 5,413,586 Date filed: September 14, 1993 Abstract: The invention describes a pulmonary embolism prevention filter of the type made from an elastic wire with remanent spring effect, characterized int hat it comprises at least two wires (100, 200), each spirally shaped. The said two wires (100, 200) have at least substantially the same length and are connected in the vicinity of their ends. Excerpt(s): The present invention relates to the field of anti-pulmonary embolism filters. More precisely, the present invention relates to improvements to the anti-pulmonary embolism filter described in French Patent Applications No. 89 13160 of 9, Oct. 1989 and No. 89 16538 of 14, Dec. 1989 and PCT Patent Application No. PCT/FR90/00721 filed on 9, Oct. 1990. Various anti-pulmonary embolism filters have already been proposed. Regarding this point, reference may be made for example to documents FR-A-2,616,666, EP-A-121,447, EP-A-323,333 and DE-A-3,203,410. Web site: http://www.delphion.com/details?pn=US05413586__

Patents

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81

Assay for soluble crosslinked fibrin polymers Inventor(s): Francis; Charles W. (Rochester, NY), Marder; Victor J. (Rochester, NY) Assignee(s): Research Corporation Technologies, Inc. (tucson, Az) Patent Number: 5,206,140 Date filed: March 26, 1990 Abstract: This invention relates to an assay for fibrin polymers for use in the diagnosis of patients at risk of thrombosis and in monitoring the effects of treatment in such patients. More particularly, the present invention relates to an assay for soluble crosslinked fibrin polymers in patent samples involving the in vitro treatment of the sample with a proteolytic enzyme such as t-PA which generates the D-dimer fragment of soluble fibrin polymers. The amount of D-dimer formed is determined by an immunoassay specific for D-dimer. The measurement of D-dimer is thus a useful reflection of the hypercoagulability state and the test may be useful for assessing pre-thrombotic or thrombotic disorders such as myocardial infarction, pulmonary embolism and deep vein thrombosis, as well as for soluble fibrin formation in neoplastic, immune, inflammatory states, or other pathologic conditions, and for evaluations of therapy such as with anticoagulants that are used to treat these conditions. Excerpt(s): The present invention relates to a novel assay for use in the diagnosis of patients at risk of thrombosis and in monitoring the effects of treatment of such patients. More particularly, the present invention relates to a novel method for measuring the amount of soluble crosslinked fibrin polymers involving the in vitro treatment of patient sample, e.g. plasma, with a plasminogen activator such as tissue-plasminogen activator (t-PA) or active plasmin to generate D-dimer products of soluble fibrin polymers, the amount of D-dimer generated being directly proportional to the amount of soluble crosslinked fibrin polymers in the patient sera, the amount being indicative of thrombin and factor XIII activation, i.e. on-going thrombosis, that may indicate a hypercoagulable state. Much effort has been expended in recent years to develop methods for measuring activation products of fibrinogen. The reason is that fibrinogen to fibrin conversion may be involved in many different pathological conditions, including the prethrombotic state and disseminated intravascular coagulation. Nevertheless, the presently available methods for direct determination of circulating fibrin (soluble fibrin) are not practical since they are either difficult to perform or suffer lack of sensitivity and of specificity. Such methods have consisted, among others, of chemical purification and chromatographic assay of soluble fibrin in human plasma or by a serial dilution protamine sulfate testing. In theory, fibrin formation can be detected indirectly by determination of released fibrinopeptides. However, apart from being difficult to analyze, the fibrinopeptides have short half-lives and may not give the same information as direct determination of soluble fibrin. Web site: http://www.delphion.com/details?pn=US05206140__

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•

Capillary zone electrophoretic detection of biological thiols and their S-nitrosated and oxidized derivatives Inventor(s): Loscalzo; Joseph (50 Pacella Dr., Dedham, MA 02026), Stamler; Jonathan (220 Marlborough St., #1, Boston, MA 02116) Assignee(s): None Reported Patent Number: 5,346,599 Date filed: January 26, 1993 Abstract: Individual thiols present in a biological sample are separated and identified using capillary electrophoresis. S-nitrosated and oxidized derivatives of thiols are also detected using capillary electrophoresis. In addition, capillary electrophoresis may be performed on samples which have been treated with an acid, so as to achieve a pH between 2.0 and 6.8, in order to further enhance detection. Separation and detection of S-nitrosated derivatives of thiols provides a means for monitoring the extent of a disease state associated with abnormal levels of nitric oxide. Such disease states include septic shock, cardiogenic shock, hypovolemic shock, atherosclerosis, hyperhomocysteinemia, venous thrombosis, arterial thrombosis, coronary occlusion, pulmonary embolism, cerebrovascular accidents, vascular fibrosis, ectopia lentis, osteoporosis, mental retardation, skeletal deformities, pulmonary hypertension, malignancy, infections and central nervous system disorders. Excerpt(s): This invention was made with government support under HL40411, HL43344, National Research Fellowship F32 HL08177, and K04 HL02273 awarded by the National Institutes of Health. The government has certain rights in the invention. The invention relates to a method for separating and detecting individual thiols present in a sample, by subjecting the sample to capillary electrophoresis. This method is also used to detect S-nitrosated and oxidized derivatives of thiols. The invention provides an additional method in which the sample is treated with an acid in order to achieve a pH which is between 2.0 and 6.8, just prior to subjecting it to capillary electrophoresis. The fraction of sulfur existing as free sulfhydryl moieties (RSH) in eukaryotic cells largely resides in the low-molecular-weight compounds, glutathione, cysteine, and homocysteine (Jocelyn, Biochemistry of the SH Group; Academic Press: London/New York, pp. 1-46 (1972)). Although these compounds exploit unique aspects of sulfur chemistry to execute various thiol-specific biochemical functions, they share many physical properties and a common chemistry, as illustrated by the conversion of reduced thiols to S-nitrosothiols and thionitrites upon treatment with certain oxides of nitrogen. (Oae, S. et al., Org. Prep. Proced. Int. 15:165-198 (1983)). Each of the Snitrosated biological thiol derivatives are reactive chemical species possessing innate antiplatelet and vasodilatory properties not manifested by equimolar amounts of thiol and nitric oxide alone (Loscalzo, J., J. Clin. Invest. 76:703-708 (1985); Ignarro et al., J. Pharmacol. Exp. Ther. 218:739-749 (1981); and Mellion et al., J. Mol. Pharmacol. 23:653654 (1983)). Web site: http://www.delphion.com/details?pn=US05346599__

Patents

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Detection of early platelet activation and prediagnosis of thrombotic events Inventor(s): Aiken; Martha L. (Tyler, TX), Painter; Richard G. (Tyler, TX) Assignee(s): Board of Regents, the University of Texas System (austin, Tx) Patent Number: 5,256,538 Date filed: March 8, 1991 Abstract: The present invention relates to a highly sensitive diagnostic/prediagnostic test to identify persons at risk of a thrombotic event. Thrombotic events include myocardial infarction, deep venous thrombosis, pulmonary embolism, thromboembolic stroke pulmonary embolism deep venous and cardiovascular disease. The test is based on the early detection of elevated levels of resting platelet surface thrombospondin. The present invention also includes methods of determining the presence of thrombospondin on the surface TSP receptors of resting platelets in a biological sample. An anti-thrombospondin monoclonal antibody which is specific for thrombospondin on resting platelets is also disclosed. A diagnostic test in the form of a test kit for the determination of thrombospondin levels in a patient sample, and also for the prediagnosis of persons at risk for thrombotic events, is also described. Excerpt(s): The present invention relates to the field of thrombotic disorders and diagnostic tests to predict their onset. More specifically, the present invention relates to the field of early diagnostic tests for the prediction of thrombotic events such as myocardial infarction, thromboembolism, stroke and related conditions. In that the method whereby these thrombotic events are predicted is based on the presence of thrombospondin on the surface of a very small number of activated cells and more importantly a much larger number of resting platelets, the present invention relates to methods of analyzing resting platelets and their associated molecules. More specifically, the present invention relates to methods of analyzing resting platelets to qualitatively and quantitatively measure thrombospondin present on TSP receptors on the surface of resting platelets in a biological sample. Most specifically, the present invention relates to the field of determining thrombospondin concentrations as present on the population of resting platelets in a biological sample. The invention also relates to the field of monoclonal and polyclonal antibodies, more particularly, a specific monoclonal antibody capable of immunologically binding with thrombospondin present on the surface of resting platelet surface TSP receptors is most preferably used in the described diagnostic and predictive methods. Web site: http://www.delphion.com/details?pn=US05256538__

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Device with a locating member for removably implanting a blood filter in a vein of the human body Inventor(s): Bovyn; Gilles (03, rue Monseigneur Morelle, 22000 Saint-Brieuc, FR), Gory; Pierre (02, Boulevard Clemenceau, 22000 Saint-Brieuc, FR) Assignee(s): None Reported Patent Number: 5,300,086 Date filed: December 2, 1992 Abstract: This device comprises an elastic guide wire onto which is fitted a semi-rigid tubular mandrel which is in turn fitted into a thin-walled tubular sheath. A catheter in the form of an easily divisible flexible tube has a distal end that permanently holds a

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blood filter. The catheter's proximal end receives a locating member that can be confined under the skin of a patient to insure that no infection develops. After the filter is temporarily implanted, a removable strengthening cable can be inserted into the catheter to advance the filter along the sheath to a chosen position in a vein, in particular the inferior vena cava, of the patient. The locating member makes it easy to remove the filter whenever the risk of pulmonary embolism is no longer present. Excerpt(s): This invention relates to a device for temporarily implanting, in a vein of the human body, and in particular in the inferior vena cava of a patient, a blood filter, and more particularly a blood filter of the type that is elastically expandable in the radial direction. The function of blood filters is to hold back the blood clots that may form in the course of phlebitis or other vascular or cardiovascular disorders, in order to prevent their migration towards the pulmonary arteries where they could cause an embolism. The filters generally used for this purpose have the shape of a small umbrella consisting of a plurality of flexible branches that can be radially expanded. In the rest position (retracted state) the branches extend approximately parallel to one another and occupy a reduced dimension in the radial direction, and this allows them to be positioned in a vein. Once in place inside the vein, the branches spread automatically outward and are immobilized against the wall of the vein, thereby anchoring the filter at the desired site. Web site: http://www.delphion.com/details?pn=US05300086__ •

Immunoassay and kit for in vitro detection of soluble DesAABB fibrin polymers Inventor(s): Gargan; Paul E. (Southbend, IN), Pleasants; Julian R. (Granger, IN), Ploplis; Victoria A. (Leuven, BE) Assignee(s): American Biogenetic Sciences, Inc. (copiague, Ny) Patent Number: 5,453,359 Date filed: July 2, 1993 Abstract: An in vitro immunoassay to detect and quantitate soluble crosslinked and non-crosslinked DesAABB fibrin polymers in a sample from a subject. The assay can be used to support a diagnosis of, to evaluate, and to monitor, in a mammalian subject, a thrombotic event, including, but not limited to, myocardial infarction, pulmonary embolism, stroke and deep vein thrombosis. Excerpt(s): The subject invention relates a method for the production of monoclonal antibodies. The method utilizes an immunized germfree animal. The invention also provides a method for the use of such monoclonal antibodies, and polyclonal antibodies derived from an immunized germfree animal, for in vitro and in vivo clinical diagnostics and therapeutics. Also, the subject invention provides a fibrin-specific monoclonal antibody. Kohler and Milstein are generally credited with having devised the techniques that successfully resulted in the formation of the first monoclonal antibody-producing hybridomas (G. Kohler and C. Milstein, 1975, Nature 256, 495-497; 1976, Eur. J., Immunol. 6, 511-519). By fusing antibody-forming cells (spleen Blymphocytes) with myeloma cells (malignant cells of bone marrow primary tumors) they created a hybrid cell line, arising from a single fused cell hybrid (called a hybridoma or clone). The hybridoma had inherited certain characteristics of both the lymphocytes and the myeloma cell lines. Like the lymphocytes, the hybridoma secreted a single type of immunoglobulin; moreover, like the myeloma cells, the hybridoma had the potential for indefinite cell division. The combination of these two features offered distinct advantages over conventional antisera. Antisera derived from vaccinated

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animals are variable mixtures of polyclonal antibodies which never can be reproduced identically. Monoclonal antibodies are highly specific immunoglobulins of a single type. The single type of immunoglobulins secreted by a hybridoma is specific to one and only one antigenic determinant, or epitope, on the antigen, a complex molecule having a multiplicity of antigenic determinants. For instance, if the antigen is a protein, an antigenic determinant may be one of the many peptide sequences (generally 6-7 amino acids in length; M. Z. Atassi, 1980, Molec. Cell. Biochem. 32, 21-43) within the entire protein molecule. Hence, monoclonal antibodies raised against a single antigen may be distinct from each other depending on the determinant that induced their formation; but for any given hybridoma, all of the antibodies it produces are identical. Furthermore, the hybridoma cell line is easily propagated in vitro or in vivo, and yields monoclonal antibodies in extremely high concentration. Web site: http://www.delphion.com/details?pn=US05453359__ •

Low molecular weight bicyclic thrombin inhibitors Inventor(s): Bachand; Benoit (Montreal, CA), Dimaio; John (Montreal, CA), Doherty; Annette Marian (Paris, FR), Edmunds; Jeremy John (Ypsilanti, MI), Gillard; John W. (Baie d'Urfe, CA), Levesque; Sophie (Laval, CA), Preville; Patrice (Saint-Charles Borromee, CA), Siddiqui; M. Arshad (Saint-Laurent, CA), St-Denis; Yves (Montreal, CA), Tarazi; Micheline (Montreal, CA) Assignee(s): Biochem Pharma Inc. (laval, Ca) Patent Number: 6,057,314 Date filed: June 23, 1997 Abstract: This invention relates to the discovery of heterocyclic competitive inhibitors of the enzyme thrombin, their preparation, and pharmaceutical compositions thereof. As well, this invention relates to the use of such compounds and compositions in vitro as anticoagulants and in vivo as agents for the treatment and prophylaxis of thrombotic disorders such as venous thrombosis, pulmonary embolism and arterial thrombosis resulting in acute ischemic events such as myocardial infarction or cerebral infarction. Moreover, these compounds and compositions have therapeutic utility for the prevention and treatment of coagulopathies associated with coronary bypass operations as well as restenotic events following transluminal angioplasty. Excerpt(s): This invention relates to compounds useful for the treatment of thrombotic disorders, and more particularly to novel heterocyclic inhibitors of the enzyme thrombin. Inordinate thrombus formation on blood vessel walls precipitates acute cardiovascular disease states that are the chief cause of death in economically developed societies. Plasma proteins such as fibrinogen, proteases and cellular receptors participating in hemostatis have emerged as important factors that play a role in acute and chronic coronary disease as well as cerebral artery disease by contributing to the formation of thrombus or blood clots that effectively diminish normal blood flow and supply. Vascular aberrations stemming from primary pathologic states such as hypertension, rupture of artheroslerotic plaques or denuded endothelium, activate biochemical cascades that serve to respond and repair the injury site. Thrombin is a key regulatory enzyme in the coagulation cascade; it serves a pluralistic role as both a positive and negative feedback regulator. However, in pathologic conditions the former is amplified through catalytic activation of cofactors required for thrombin generation as well as activation of factor XIII necessary for fibrin cross-linking and stabilization. In addition to its direct effect on hemostasis, thrombin exerts direct effects on diverse cell

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types that support and amplify pathogenesis of arterial thrombus disease. The enzyme is the strongest activator of platelets causing them to aggregate and release substances (eg. ADP TXA.sub.2 NE) that further propagate the thrombotic cycle. Platelets in a fibrin mesh comprise the principal framework of a white thrombus. Thrombin also exerts direct effects on endothelial cells causing release of vasoconstrictor substances and translocation of adhesion molecules that become sites for attachment of immune cells. In addition, the enzyme causes mitogenesis of smooth muscle cells and proliferation of fibroblasts. From this analysis, it is apparent that inhibition of thrombin activity constitutes a viable therapeutic approach towards the attenuation of proliferative events associated with thrombosis. Web site: http://www.delphion.com/details?pn=US06057314__ •

Method for removably implanting a blood filter in a vein of the human body Inventor(s): Bovyn; Gilles (03, rue Monseigneur Morelle, 22000 Saint-Brieuc, FR), Gory; Pierre (02, Boulevard Clemenceau, 22000 Saint-Brieuc, FR) Assignee(s): None Reported Patent Number: 5,415,630 Date filed: March 9, 1994 Abstract: A method for removably implanting a blood filter in a vein of the human body makes use of apparatus that includes an elastic guide wire onto which there can be fitted a semi-rigid tubular mandrel (itself fitted into a thin-walled tubular sheath). A catheter is provided in the form of an easily divisible flexible tube whose distal end permanently bears the blood filter, and whose proximal end is intended to receive a locating member which will be confined under the skin of the patient. After temporary implanting of the filter, a removable strengthening cable can be inserted in a removable manner in the catheter in order to displace the filter along the sheath during its positioning in a vein, in particular in the inferior vena cava of a patient. This filter can be easily removed after a certain period, when the risks of pulmonary embolism are no longer feared. Excerpt(s): This invention relates to a device for temporarily implanting, in a vein of the human body, and in particular in the inferior vena cava of a patient, a blood filter, and more particularly a blood filter of the type that is elastically expandable in the radial direction. The function of blood filters is to hold back the blood clots that may form in the course of phlebitis or other vascular or cardiovascular disorders, in order to prevent their migration towards the pulmonary arteries where they could cause an embolism. The filters generally used for tilts purpose have the shape of a small umbrella consisting of a plurality of flexible branches that can be radially expanded. In the rest position (retracted state) the branches extend approximately parallel to one another and occupy a reduced dimension in the radial direction, and this allows them to be positioned in a vein. Once in place inside the vein, the branches spread automatically outward and are immobilized against the wall of the vein, thereby anchoring the filter at the desired site. Web site: http://www.delphion.com/details?pn=US05415630__

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Method of and apparatus for producing alternating pressure in a therapeutic device Inventor(s): Proctor; Richard D. J. (5 Rocky Hill Dr., Litchfield, NH 03051), Scheuhing; Robert B. (16 Spaulding Dr., Merrimack, NH 03054) Assignee(s): None Reported Patent Number: 5,109,832 Date filed: December 7, 1990 Abstract: A method of and apparatus are disclosed for producing alternating pressure in a theapeutic device used to apply compressive forces to a portion of a human body to enhance venous blood flow and prevent venous thrombosis and pulmonary embolism in surgical patients. The apparatus comprises at least two sets of a plurality of inflatable bladders or chambers arranged in alternating relation to one another. All the bladders of one set are inflated and deflated alternately with the deflation and inflation of all the bladders of the other set to produce a therapeutic alternate chamber pumping action on that portion of the body being treated. A single fluidic flip-flop device controls the supply and venting of pressurized fluid to and from the chambers. Excerpt(s): The present invention relates to medical apparatus and methods and more particularly to a non-invasive method of and apparatus for producing alternating pressures in a device used to apply compressive forces to a portion of a body for the therapeutic purpose of enhancing venous blood flow to prevent venous thrombosis and pulmonary embolism in surgical patients. In the prevention of venous thrombosis in surgical patients, it is well known that intermittent application of pressure to the lower extremities significantly reduces the occurrence of deep vein thrombosis which can lead to pulmonary embolism. Many prior art devices have been proposed for applying intermittent pressure to body extremities, especially the legs, by means of one or more inflatable bladders or cuffs disposed about the legs of a patient. The bladders are then periodically inflated with air or another fluid at a predetermined frequency. Typical of such devices is that disclosed in U.S. Pat. No. 2,140,898 which requires a source of electricity for operation. In addition to the prior art devices which apply a uniform intermittent pressure to an extremity by means of one or more bladders or cuffs, therapeutic devices are also known for applying pressure to an extremity in a peristaltic or quasi-peristaltic manner by the sequential inflation of a series of annular bladders arranged about the limb and spaced along the length thereof. One such known device is disclosed in U.S. Pat. No. 3,862,629. That device requires a plurality of series-connected bladders which, after attaining steady state operation, operate in a quasi-peristaltic mode and apply substantially sinusoidal compressive forces to the limb of the patient. Because an individual valve assembly is used with each bladder, as many as twenty valve assemblies are required for a single therapeutic device thereby making the device quite costly to produce. In addition, the valve assemblies of this prior art device are constructed with a number of surfaces which are in sliding or frictional contact. In view of the relatively low operating pressures (1-2 psi), and the series connection of the valve assemblies, a single sticking or marginally operative valve assembly could diminish the therapeutic effectiveness of the device or possibly interrupt operation of the device altogether, thereby rendering the device useless. Moreover, because of the series connection of the valve assemblies, stable operation of the device is not achieved until the fluid pressure serially inflates all the bladders which may take one minute or more depending on the number of valve assemblies connected in series and the inflation period of the valve assemblies. Web site: http://www.delphion.com/details?pn=US05109832__

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Method of preventing or reducing venous thrombosis using a thromboxane A.sub.2 receptor antagonist in conjunction with heparin and combination Inventor(s): Schumacher; William A. (Newtown, PA) Assignee(s): E. R. Squibb & Sons, Inc. (princeton, Nj) Patent Number: 4,900,723 Date filed: April 29, 1988 Abstract: A method is provided for preventing or reducing deep vein thrombosis and/or pulmonary embolism by administering a thromboxane A.sub.2 receptor antagonist in conjunction with heparin. A combination of thromboxane A.sub.2 receptor antagonist and heparin is also provided. Excerpt(s): The present invention relates to a method for preventing or reducing deep vein thrombosis (DVT), and/or pulmonary embolism, especially following surgery, by administering a thromboxane A.sub.2 receptor antagonist with the anticoagulant heparin and to a synergistic combination of thromboxane A.sub.2 receptor antagonist and heparin. The use of thromboxane A.sub.2 receptor antagonists for arterial thrombosis is well recognized, but their application in venous thrombosis and as adjuncts to heparin is not established. The anticoagulant heparin, which is the choice drug for preventing venous clots, is much less effective in the arterial circulation. Likewise, aspirin and other antiplatelet drugs impede arterial thrombosis, but are generally ineffective against venous thrombosis. This dichotomy exists because of important differences in the mechanisms of clot formation in the venous and arterial arms of the vascular tree. Arterial clots (white thrombus) consist primarily of platelets, which have aggregated in response to vessel injury. Venous clots (red thrombus) differ in that stasis of blood flow and activation of coagulation (plasma thickening) combine with vessel damage to generate a red blood cell rich mass. This is not to say that coagulation is not involved in arterial thrombosis, or that platelets do not have a role in venous clot formation, only that the magnitude of impact differs in each particular instance. There is indeed room for improvement over the use of heparin for prophylaxis of DVT, especially after total hip replacement (Hampson et al., "Failure of low-dose heparin to prevent deep-vein thrombosis after hip-replacement arthroplasty." Lancet 2:795-797, 1985). Recent therapeutic approaches have focused on combination therapies involving agents selective for the individual components responsible for venous clot formation, which include vessel injury, blood coagulation and blood stasis. It has been suggested that inhibition of two of these three components would maximize the potential for preventing DVT (Comerota et al, "Combined dihydroergotamine and heparin prophylaxis of postoperative deep vein thrombosis; proposed mechanism of action." Am. J. Surgery 150:39-44, 1985). Dihydroergotamine is a vasoactive drug used to increase venous tone and thereby reducing blood stasis in vessels where pooling of blood is a potential thrombotic hazard. Dihydroergotamine has been found to act synergistically with heparin in reducing the incidence of post-surgical DVT (Kakkar et al., "Prophylaxis for postoperative deep-vein thrombosis." JAMA 241:39-42, 1979). A combination of dihydroergotamine and heparin with lidocaine has been marketed by Sandoz (Embolex) for prophylaxis against DVT and pulmonary embolism associated with major abdominal, thoracic or pelvic surgery. Web site: http://www.delphion.com/details?pn=US04900723__

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Neuromuscular electrical stimulation of the foot muscles for prevention of deep vein thrombosis and pulmonary embolism Inventor(s): Czyrny; James Joseph (21 Snyderwoods Ct., Amherst, NY 14226), Hirsh; Jack (21 Cottage Avenue, Hamilton, Ontario, CA L8P 4G5), Kaplan; Robert Edward (69 Dorchester Rd., Buffalo, NY 14222), Unsworth; John Duncan (c/o Vasotech Corp. 7 Innovation Drive, Suite 107, Flamborough, Ontario, CA L9H 2H9) Assignee(s): None Reported Patent Number: 6,615,080 Date filed: March 29, 2001 Abstract: A single channel neuromuscular electrical stimulation (NMES) device for the prevention of deep vein thrombosis (DVT), pulmonary embolism (PE), lower extremity edema, and other associated conditions by electrical stimulation of the muscles of the foot muscles. An electrical signal generator produces a square wave pattern of variable frequency, duration, intensity, ramp time, and stimulation on-off cycle. Surface electrodes are positioned over the foot muscles and are attached to the stimulator by various means. The stimulator is programmed in a manner to stimulate the foot muscles to reduce pooling of the blood in the soleal veins of the calf This is accomplished by only stimulating the soles of the feet. Excerpt(s): This invention relates to the use of single channel Neuromuscular Electrical Stimulation (NMESS ) of the lower extremity for the prevention of Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE) by reducing the pooling of blood in the soleal veins of the calf. Venous thromboembolic disease (VTED) continues to be a cause of significant morbidity and mortality for individuals immobilized during prolonged travel, after orthopedic surgery, neurologic disorders, and a variety of other conditions. Virchow in 1845, postulated that changes in blood flow, vessel wall, and blood constituents were responsible for venous thrombosis.sup.1 Studies have shown that at least two of the three factors are nee de d to trigger thrombosis. Reduction of blood flow, especially in the venous sinuses of the calf muscles has long been recognized as an important risk factor.sup.2,3,4 The venous pooling triggers coagulation and at the same time consumes local anticoagulants. This explains the high risk of DVT and PE in spinal cord injury, stroke, and post-surgery where immobility of the lower limbs occurs. Web site: http://www.delphion.com/details?pn=US06615080__

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Parameter selection and electrode placement of neuromuscular electrical stimulation apparatus Inventor(s): Foley; Russell A. (Fayetteville, GA), Leahy; JoAnn (Atlanta, GA), Powell, III; Jack H. (Newman, GA), Seaman; Joseph J. (Newman, GA) Assignee(s): Medtronic, Inc. (minneapolis, Mn) Patent Number: 5,358,513 Date filed: December 9, 1992 Abstract: A method of neuro-muscular electrical stimulation for treatment and prevention of venous thrombosis and pulmonary embolism employs electrodes attached to an anterior portion of a patient's knee, immediately proximal the common peroneal nerve. Electrical stimulation is comprised of trains of pulse modulated sinusoids where each pulse has a rise time of about 1 second, a fall time of about 0.5

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seconds, and a plateau (on time) of about 1 to 10 seconds. Peroneal nerve stimulation is achieved thereby causing passive stretching of the gastrocnemius and soleus muscles (major posterior calf muscles) rather than a contraction for creating a blood pumping action. Excerpt(s): This invention relates generally to use of neuro-muscular electrical stimulation of the lower extremity for treatment and prevention of thrombosis, and more particularly to electrical stimulation of anterior to anterior lateral compartments exclusively of a patient's leg to promote venous blood flow. Prevention of venous thrombosis and pulmonary embolism is one of the major concerns of clinicians nationally. Pulmonary embolism is estimated to be the third most common cause of death in the United States. Hospitalization due to venous thrombosis and pulmonary embolism are associated in ranges of 300,000 to 600,000 a year and results in as many as 50,000 to 200,000 deaths a year as a result of pulmonary embolism. Patients undergoing various types of surgical procedures as well as trauma are at high risk for developing deep vein thrombosis (DVT) and pulmonary embolism (PE). Averages demonstrate that the orthopedic patient population appear to be especially prone to thrombosis with highest risk in those patients with hip, tibial and knee fractures. Web site: http://www.delphion.com/details?pn=US05358513__ •

Pharmaceutical compositions containing low molecular weight dermatan sulfate for the therapy of pulmonary embolism Inventor(s): Baldazzi; Claudia (Ozzano Emilia, IT), Barbanti; Maria (Bologna, IT), Zamboni; Villiam (Bologna, IT) Assignee(s): Alfa Wassermann S.p.a. (alanno, It) Patent Number: 5,817,645 Date filed: December 12, 1996 Abstract: The prevention and therapy of pulmonary embolism with pharmaceutical compositions containing low molecular weight dermatan sulfate is described. These pharmaceutical compositions are administered by subcutaneous, intramuscular or intravenous route at a daily dosage between 200 and 3000 mgs of active principle. The low molecular weight dermatan sulfate preferred in carrying out the invention has an average molecular weight equal to 5500.+-.1100 Daltons and is obtained by depolymerization of the dermatan sulfate of natural origin in the presence of hydrogen peroxide and cupric ions. Excerpt(s): This invention relates to prevention and treatment of pulmonary embolism. The pulmonary embolism is a pathology of remarkable clinical and socioeconomical importance which comes up as serious complication of the deep venous thrombosis and represents the more common cardiovascular disease after the ischaemic heart diseases and the stroke ›Giuntini C. et al., Chest 107, 3S-9S (1995)!, with an incidence growing with the age ›Kniffin W. D. Jr, et al., Arch. Int. Med. 154, 861-6 (1994)!. Every year it causes only in the United States about 50000 cases of death ›Kniffin W. D. Jr, et al., Arch. Int. Med. 154, 861-6 (1994)! and 250000 hospitalizations ›Anderson F. A. Jr, et al., Arch. Int. Med. 151, 933-8 (1991)!. The pulmonary embolism can be both primary or idiopathic and secondary; in this latter case it is mainly subsequent to surgical operations or to traumas but it can come also from cardiovascular, tumoral and systemic diseases ›Giuntini C., et al., Chest 107, 3S-9S (1995)!. The pulmonary embolism is often asymptomatic and frequently it is not diagnosed, as the post-mortem examinations

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show, also because the diagnostic methods at present available are insufficiently used because they are complicated, expensive and scarcely sensitive ›Agnelli G., Chest 107, 39S-43S, (1995)!. The invariability of the death rate in the last 30 years ›Lilienfeld D. E., et al., Chest 98, 1067-72, (1990)! is an evident index of the poor present ability to face in an efficacious manner this kind of pathology and in particular of the lack of a reliable and safe pharmacological therapy. The anticoagulants, like heparin, low molecular weight heparins and warfarin, because of their ability to prevent the formation of new thrombi and to stop the growth of those existing, are the drugs more commonly used in the prevention and cure of the pulmonary embolism ›Stein P. D., Clinics in Chest Medicine 16, 229-33, (1995)!. The thrombolytic drugs, like urokinase, that carry out a progressive action of dissolution of the thrombus, are less used. The use of the anticoagulants and also more that of the thrombolytic drugs is coupled to a very high risk of hemorrhages, as the people skilled in the field know. Moreover the great differences of individual pharmacokinetic response make necessary the continuous check at hospital level, except for the low molecular weight heparins. The anticoagulants and the thrombolytic drugs at present available are used notwithstanding the risks and the complexity of use because first choice drugs totally lack in the therapy of the pulmonary embolism. Web site: http://www.delphion.com/details?pn=US05817645__ •

Processes for the preparation of low-affinity, low molecular weight heparins useful as antithrombotics Inventor(s): Hirsh; Jack (Hamilton, CA), Knobloch; James E. (Cross Plains, WI), Shaklee; Patrick N. (Pardeeville, WI), Weitz; Jeffrey I. (Ancaster, CA), Young; Edward (Oakville, CA) Assignee(s): Hamilton Civic Hospitals Research Development Inc. (ca) Patent Number: 5,767,269 Date filed: October 1, 1996 Abstract: The present invention generally relates to a processes for preparing low affinity, low molecular weight heparins (LA-LWM-heparins) which are endowed with pharmacological and therapeutic properties that are surprisingly advantageous. In one embodiment, the process comprises: (1) nitrous acid depolymerization of unfractionated heparin to yield low molecular weight heparin (LMWH); (2) oxidation of the resulting LMWH to open the ring structures the nonsulfated uronic acid moieties using, for example, sodium periodate; and (3) reduction of the oxidized LMWH to reduce the aldehydes (to alcohols) formed during the depolymerization and oxidation steps using, for example, sodium borohydride. The resulting LA-LMW-heparins are capable of inactivating thrombin bound to fibrin within a thrombus or clot, whereby the ability of clot-bound thrombin to catalytically promote further clot accretion is substantially diminished or eliminated. As such, the resulting LA-LMW-heparins are useful for preventing thrombosis in the circuit of cardiac bypass apparatus and in patients undergoing renal dialysis, and for treating patients suffering from or at risk of suffering from thrombus-related cardiovascular conditions, such as unstable angina, acute myocardial infarction (heart attack), cerebrovascular accidents (stroke), pulmonary embolism, deep vein thrombosis, arterial thrombosis, etc. Excerpt(s): The present invention relates generally to processes for the preparation of low affinity, low molecular weight heparins (LA-LMW-heparins) which are useful, inter alia, as antithrombotics. More particularly, the present invention relates to processes for the preparation of LA-LMW-heparins, the processes generally comprising: (1)

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depolymerizing unfractionated heparin; (2) oxidizing the resultant low molecular weight heparin; and (3) reducing the oxidized, low molecular weight heparin. The resulting LA-LMW-heparins have unexpected and surprisingly superior pharmacological and therapeutic properties. Thrombosis is a pathological manifestation of the clotting cascade in blood vessels. The clotting cascade is a complex biological process which results in the formation of a clot or thrombus composed of platelets and fibrin. Thrombin is bound to fibrin in the clot where it is catalytically active and able to amplify its production over 1000-fold by activating clotting factors in the surrounding blood. The ability of blood to generate thrombin is fundamental to the prevention of excessive bleeding at wound sites (hemostasis). Thrombin is important in hemostasis because it stimulates platelet aggregation and fibrin formation when a blood vessel is severed. Therefore, an ideal antithrombin would be an agent which can pacify the clot by inactivating fibrin-bound thrombin at concentrations which do not produce abnormal bleeding resulting from inhibition of thrombin production in the general circulation. Thrombosis, which can complicate atherosclerosis, can cause partial or total occlusion of the affected blood vessel, thereby leading to a number of important cardiovascular complications, including unstable angina, acute myocardial infarction (heart attack), cerebral vascular accidents (stroke), pulmonary embolism, deep vein thrombosis and arterial thrombosis. Such diseases are a major cause of disability and mortality throughout the world, but particularly in Western societies. Moreover, thrombin and, in particular, surface-bound thrombin play a role in thrombus formation in cardiac bypass circuits, after angioplasty and during and after thrombolytic therapy for acute myocardial infarction. Therefore, patients undergoing these procedures must be treated with very high doses of heparin to prevent thrombosis. Although these high doses of heparin may effectively prevent clotting, they can give rise to serious bleeding complications. Web site: http://www.delphion.com/details?pn=US05767269__ •

Removable blood filter Inventor(s): Blom; Paul H. (5812 Fifth Ave. M-12, Pittsburgh, PA 15232) Assignee(s): None Reported Patent Number: 6,436,121 Date filed: April 30, 2001 Abstract: The present invention provides a blood filter comprising a plurality of central struts, the distal ends thereof intersecting at a vertex, a hollow tubular member having distal and proximal ends in fluid communication, and having at least one vertical strut extending therefrom, and means for retaining the plurality of central struts within the hollow tubular member. At least the outer layer of the hollow tubular member is made of a flexible material which resists the ingrowth of tissue around the central struts of the filter. The blood filter of the present invention can reduce the occurrence of circulatory occlusions, including pulmonary embolism, in patients and because of the hollow tubular member being made from a material which resists the ingrowth of tissue, it can easily be removed from the venous system of the patient when there is no longer an indication for its use. Excerpt(s): The present invention relates in general to blood filtration, and more specifically to a blood filter that is removable. Deep vein thrombosis is a condition in which a blood clot, called a thrombus, develops in the vein of a patient. The thrombus or a portion of it may break off, in which case it is called an embolus, travel through the

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venous system and become lodged in the patient's heart or lungs. Emboli lodged in the lungs, a condition termed pulmonary embolism, are potentially dangerous because the emboli may obstruct the arteries of the lung and lead to death. It is estimated that deep vein thrombosis afflicts approximately 200,000 people every year. Deep vein thrombosis and pulmonary embolism most often occur in bedridden patients, but may also occur in ambulatory or otherwise healthy people. Deep vein thrombosis is a major complication for orthopedic surgical patients, such as those who have undergone major hip or knee surgery and for patients suffering from cancer or other chronic illnesses. Web site: http://www.delphion.com/details?pn=US06436121__ •

Self applied device and method for prevention of deep vein thrombosis Inventor(s): Katz; Amiram (15 Beaver Brook Rd., Weston, CT 06470), Katz; Orly (15 Beaver Brook Rd., Weston, CT 06470) Assignee(s): None Reported Patent Number: 6,002,965 Date filed: June 10, 1998 Abstract: An elongated rectangular cuff having fasteners and electrodes with an attached control unit for providing a predetermined electrical signal to the electrodes. The predetermined electrical signal is substantially a square wave with a duration of between 0.1 and 0.3 milliseconds, a frequency of between 0.1 and 0.5 Hertz, with 5 to 15 repetitions delivered every 5 to 15 minute intervals. The control unit provides a controllable intensity of between 1 to 20 milliamperes. The cuff or sleeve, when wrapped around a user's leg and positioned below the knee such that the electrodes contact the calf muscles, causes a muscle and nerve stimulation resulting in contraction of the calf muscle. Blood flow is therefore increased regardless of body position or a movement greatly decreasing the possibility of developing deep vein thrombosis or pulmonary embolism, which may be fatal. In addition it reduces ankle edema and leg discomfort associated with prolonged sitting. A predetermined applied signal is safe with little risk of harm to the user. Additionally, preferably the control unit has a single external control for controlling intensity preventing a user from applying an inappropriate signal. A simple to use, compact device and method is disclosed that can safely be used by individuals having no prior knowledge of anatomy, effectively during extended periods of sitting or immobility, such as when traveling. Excerpt(s): This invention relates to an electronic stimulator, and more specifically to an electronic nerve and muscle stimulator and method useful for preventing venous thrombo embolism, venostasis, varicose veins, ankle edema, and leg discomfort resulting from prolonged sitting that can be self administered by a patient. There are a large number of diagnosed cases of deep vein thrombosis, DVT, in the United States annually. There are also a large number of fatal cases of pulmonary embolism, PE, many of which can be prevented with appropriate measures, such as pharmacological or mechanical. Prolonged sitting, such as when traveling or working long hours, can aggravate or promote DVT or PE. It can also cause ankle edema and leg discomfort. Studies have indicated that about one-fifth of the sudden natural deaths associated with commercial air travel that were brought to the London Coroner from Heathrow Airport were due to pulmonary embolism. There is a need for a device that helps to stimulate blood flow so as to prevent DVT and PE during the above mentioned circumstances. One such device is disclosed in U.S. Pat. No. 5,643,331 entitled "Method and Device For Prevention of Deep Vein Thrombosis" issuing to Katz on Jul. 1, 1997, which is herein

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incorporated by reference. Therein disclosed is an electrical stimulator generating a square wave pattern having a controllable duration ranging from 0.1 to 0.3 milliseconds, a controllable frequency ranging between 0.001 to 0.5 cycles per second, and a controllable intensity ranging from 1 to 20 milliamperes. An electrode is positioned externally at or near the tibial nerve at the popliteal fossa to deliver the electrical signal. This signal stimulates the nerve, causing a muscle contraction which helping to stimulate blood flow. The increased blood flow helps in preventing deep vein thrombosis, ankle edema, and venostasis. Additionally, there are numerous transcutaneous electric nerve stimulating devices, TENS units, used to control pain. There are also similar muscle and neurological stimulating devices, MANS units, also used to control or manage pain. All of these devices deliver relatively high frequency stimuli, for example 25 to 50 Hertz. They are generally not tolerated well by patients, especially when used for relatively long periods of time. Additionally, these devices are not completely suitable for the prevention of DVT or PE. Accordingly, while these units used for pain management or control are similar, they are not suited to relatively long term use and self-application by a patient for the prevention of DVT, PE ankle edema and leg discomfort. Therefore, there is a need for a device and method of application that can easily be self-administered by a patient during extended periods of sitting or inactivity, for example during traveling in a car or a plane, or sitting for many hours while working to help prevent DVT, PE ankle edema and leg discomfort. The present invention comprises a self-contained electrical device having pre-positioned electrodes making it easy to be self-applied by a patient and worn for extended periods of time during periods of inactivity or immobility, such as when paralyzed, hospitalized or sitting during traveling or working. An elongated rectangular cuff or sleeve has straps and strips of hook and loop fastener material. Two electrodes having a predetermined position are connected to a control unit. Indicia or marking on the sleeve is placed between the two electrodes to aid in the proper positioning of the electrodes onto the leg of a patient or user. The indicia helps the user to position the electrodes without any specific knowledge of anatomy. The cuff or sleeve is sized to wrap around the calf of a user and to be securely held thereto in a proper predetermined position. The control unit attached to the cuff is preset to provide a substantially square wave signal to the electrodes having a duration of 0.3 milliseconds, a frequency of 0.1 to 0.5 Hertz with 5 to 15 repetitions delivered every 5 to 15 minutes. The control unit has a structure permitting a user to control intensity only, and only within a range of 1 to 20 milliamperes. The intensity control is the only user controlled adjustment. Web site: http://www.delphion.com/details?pn=US06002965__ •

Stable perfluorocarbon and oil emulsions Inventor(s): Clark, Jr.; Leland C. (Cincinnati, OH) Assignee(s): Children's Hospital Research Foundation, a Division of Children's (cincinnati, Oh) Patent Number: 5,536,753 Date filed: November 9, 1990 Abstract: Perfluoroindane is used as a gas transport agent in animals without causing gas or vapor pulmonary embolism. Emulsions containing perfluoroindane as the oxygen carrying component are made and infused into an animal and the perfluoroindane escapes at a very rapid rate from the animal body. The

perfluoroindane-containing liquids or angioplasty and as a blood substitute.

emulsions

are

considered

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valuable

for

Excerpt(s): The oxygen carrying capacity and lack of toxicity of perfluorinated liquids has long been established. Emulsions of fluorocarbon liquids were also used as artificial bloods. U.S. Pat. No. 3,911,138 which issued to Leland C. Clark, Jr., sets forth the various advantages and needs for artificial blood and may be referred to as further background of this invention. In that Clark patent, artificial bloods containing perfluorocyclocarbons were disclosed as useful blood substitutes. Emulsions containing emulsified particles of the perfluorocyclocarbons were also infused intravenously into experimental animals and functioned as oxygen-carbon dioxide carrying agents intravascularly. The perfluorocyclocarbons disclosed in that Clark patent were referred to as RES-phobic, which indicated that the perfluorocyclocarbons exhibited a unique property of temporary sequestration by the liver or spleen and subsequent elimination by the animal body. It was later disclosed in U.S. Pat. No. 4,150,798 which issued to Leland C. Clark, Jr. et al, that certain other perfluoropolycyclic compounds were useful as synthetic blood in perfusion media. The perfluorinated polycyclic compounds disclosed in this patent are known generally as bicyclononanes and adamantanes. Further improvements have been reported in the patent art as disclosed in U.S. Pat. No. 4,443,480 which issued to Leland C. Clark, Jr. and is directed to oxygen transport agents containing a perfluorocyclocarbon and an organoamine oxide. The brief reference to patents herein is intended only as background information leading up to this invention and is not intended to be exhaustive of the patent art. On the literature side of the prior art, reference may be made to such articles as "The Synthesis and Biological Screening of New and Improved Fluorocarbon Compounds for Use as Artificial Blood Substitutes", Final Report prepared under Contract No. 1HB6-2927 for the period Jun. 30, 1976-Dec. 31, 1978 by Robert E. Moore, Principal Investigator, as prepared for the National Institutes of Health. In this report, a number of fluorocarbons were reported as having been evaluated biologically for use in experimental animals. The biological evaluations were performed under the direction of Leland C. Clark, Jr., Ph.D. Among the approximately thirty fluorocarbons reported upon was bicyclo[4.3.0.] nonane, or otherwise known as perfluoroindane. However, perfluorindane was not considered to be viable choice, principally because it had a high vapor pressure of 32.8 mm at 37.degree. C. This value was the highest among the perfluorinated hydrocarbons reported upon in the above NIH report. It was then believed that such a high vapor pressure would cause gas embolism, consistent with earlier reports in Clark U.S. Pat. No. 3,911,138 for other analogous carbon-containing perfluorocyclo derivatives such as perfluorotrimethylcyclohexane and perfluoroisopropylcyclohexane. In the event emulsions containing such perfluorocyclohexanes were used, then breathing the vapor of the fluorocarbons, or similar fluorocarbons, that were injected balances the gas pressures in the lungs so that gas embolism does not occur. Without this gas or vapor breathing, partial pressure of the fluorocarbons in the lungs is, unlike most other gases and vapors, extremely low apparently due primarily to the poor solubility of the fluorocarbon in the blood; and its slow diffusion from the blood through the lung membrane. Hence, the total gas pressure in the blood exceeds total alveolar pressure, and gas embolism results which could lead to death in a short time. Thus, perfluorocyclocarbons that have lower vapor pressures than perfluorocyclohexanes were considered critically necessary in order to avoid special precautions or detrimental gas embolism. About ten years has elapsed since the above mentioned NIH report upon the use of perfluorocarbons as oxygen transporting agents in animals. More recently, it has been reported by Kouichi Yamanouchi et al in Chem. Parm. Bull., 33(3)12211231(1985) entitled "Quantitative Structure in Vivo Half-Life Relationships of

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Perfluorochemicals for Use as Oxygen Transporters" that a series of perfluorochemicals were investigated in terms of their quantitative structure-activity relationships. Among other findings reported in this paper, it was concluded that the vapor pressure of perfluorocarbons apparently plays an important role in the excretion system and it must be controlled within an acceptable limit so as not to cause lung damage. Web site: http://www.delphion.com/details?pn=US05536753__ •

Synthetic peptides derived from vitronectin and pharmaceutical compositions comprising them Inventor(s): Shaltiel; Shmuel (Rehovot, IL) Assignee(s): Yeda Research and Development Co. Ltd. (rehovot, Il) Patent Number: 5,491,129 Date filed: July 29, 1993 Abstract: The invention relates to synthetic peptides derived from the K.sup.348 A.sup.380 (8-40 of SEQ ID NO:1) sequence of the vitronectin molecule. The peptides modulate the biological activities of plasminogen activator inhibitor-1 (PAI-1) and are useful as active ingredients of pharmaceutical compositions for the treatment of disorders such as bleeding disorders, acute myocardial infarction, deep vein thrombosis, pulmonary embolism, disseminated intravascular coagulation, tumor cell invasion and metastasis, inflammation, liver diseases, bacterial blood infections, pregnancy toxicosis, and pathological conditions associated with the control of angiogenesis, or with nerve regeneration, or with excessive tPA-mediated proteolysis. Excerpt(s): The present invention relates to pharmaceutical compositions comprising synthetic peptides derived from vitronectin capable of modulating the biological activities of plasminogen activator inhibitor-1 (PAI-1) and to some such novel synthetic peptides. Hemostasis, the process whereby bleeding from an injured blood vessel is arrested, is characterized by the combined activity of vascular, platelet and plasma factors as well as counterbalancing mechanisms to limit the accumulation of platelets and fibrin to the area of vessel wall injury. Blood coagulation reactions form a key element of the hemostatic seal-the fibrin clot. Spreading outward from and anchoring the platelet plugs, the fibrin clot adds bulk needed for the hemostatic seal. Web site: http://www.delphion.com/details?pn=US05491129__

•

Use of biodegradable microspheres labeled with imaging energy constrast materials Inventor(s): See; Jackie R. (Fullerton, CA), Shell; William E. (Los Angeles, CA) Assignee(s): See/shell Biotechnology, Inc. (los Angeles, Ca) Patent Number: 5,186,922 Date filed: January 8, 1990 Abstract: The invention relates to an inexpensive and easy to use method of visualizing an arterial circulation, using biodegradable microspheres which are permeated with an imaging energy absorbent contrast material, such as an X-ray absorbent material, which enables the diagnosis of pulmonary embolism. The microspheres may be comprised of a variety of materials, including human albumin, and may be dyed with a number of Xray absorbent materials, or other imaging energy absorbent materials. The microspheres

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are injected into the bloodstream at a particular location such that they travel through the desired circulation, e.g. an arterial circulation and ultimately become lodged in the capillaries of a tissue of interest. Upon exposure of the arterial circulation to X-rays, blood vessels therein containing the microspheres will absorb the X-rays, causing them to show on a developed X-ray film in contrast to other blood vessels and body tissue which do not contain the microspheres that transmit the X-rays. The microspheres are designed to dissolve into the bloodstream within fifteen to thirty minutes after their introduction, the X-ray dye or other contrast material being ultimately excreted from the body via the urine or metabolized by the liver. Excerpt(s): This invention relates generally to the visualization of an arterial circulation, including e.g. diagnosis of pulmonary embolism and, more particularly, to the visualization of an arterial circulation of using biodegradable microspheres laden with a contrast material, such as an X-ray absorbent or opaque material. Decreased blood flow to various organs is a danger faced by all mammals, particularly man. A decrease in blood flow to the lungs is especially dangerous, since it is in the lungs that oxygen is incorporated into the blood for distribution throughout the body. A blood clot in the lungs, which is one cause of decreased blood flow, gives rise to a disease known as pulmonary embolism. This is one of the most difficult diseases to diagnose because the emboli can be small. The emboli are transparent to conventional X-rays and produce only non-specific symptoms. Web site: http://www.delphion.com/details?pn=US05186922__ •

Use of thrombolytic reagents for prevention of vascular disease Inventor(s): Gelfand; Mathew I. (245 Fairway Rd., Lido Beach, NY 11561) Assignee(s): None Reported Patent Number: 5,837,688 Date filed: November 27, 1996 Abstract: The present invention relates to the administration of thrombolytic reagents such as tissue plasminogen activator (t-PA), streptokinase and/or urokinase, over prolonged periods of time for prevention of vascular disease such as cerebral vascular thrombosis, pulmonary embolism, deep venous thrombus, acute myocardial infarction and fresh or aged arterial thrombi. The invention relates generally to delivery systems that provide for sustained release of thrombolytic reagents such as tissue plasminogen activator (t-PA), streptokinase and/or urokinase, over prolonged periods of time. The thrombolytic reagents may be administered, for example, transdermally, topically, intranasally or orally. Excerpt(s): Thrombolytic drugs act on the endogenous fibrinolytic system by converting plasminogen to the potent proteolytic enzyme plasmin. Plasmin in turn degrades fibrin clots and other plasma proteins. A number of thrombolytic drugs, including urokinase, streptokinase and t-PA, are currently used to treat acute vascular disease. Tissue plasminogen activator (t-PA) activates plasminogen to generate the proteinase plasmin which plays an important role in the degradation of fibrin. t-PA has been a particularly important pharmaceutical agent for use in treatment of vascular diseases due to its ability to dissolve blood clots in vivo. t-PA was originally identified and purified from natural sources. Through the use of recombinant DNA techniques, DNA clones encoding the t-PA molecule have recently been identified and characterized leading to a

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determination of the DNA sequence and deduced amino acid sequence of t-PA (U.S. Pat. No. 4,853,330). Web site: http://www.delphion.com/details?pn=US05837688__ •

Vena cava filter and method for treating pulmonary embolism Inventor(s): O'Connell; Paul T. (2414 Harrison St., Evanston, IL 60201) Assignee(s): None Reported Patent Number: 6,267,776 Date filed: May 3, 1999 Abstract: A filter is provided that is convertible from a filter configuration to an open, stent-like configuration. The filter includes a plurality of intraluminal filter elements (filter legs) that may be formed into a single cone or dual cone filter structure. A retainer secures the filter legs in the filter configuration upon initial deployment within a vessel. The retainer is then either self-releasing or removable to permit the filter legs to expand from the filter configuration into what may generally be described as an open or stentlike configuration. Excerpt(s): The invention relates generally to devices for the prevention of pulmonary embolism and, more particularly, the invention relates to a filter device for placement within the inferior vena cava that is operable to prevent embolus migration. Blood coagulation, or clotting, is the transformation of blood from a fluid initially into a semisolid gel and ultimately into an organized, fibrinous solid. Coagulation is the body's mechanism to control and stop unwanted bleeding. Despite the desirable and necessary effects of blood clotting, several undesirable effects may result from clotting which can lead to serious medical disorders and, in some instances, death. One example of such an undesirable effect of clotting is deep vein thrombosis (DVT), the formation of blood clots within the veins of the legs. DVT which is not diagnosed and successfully treated can result in the migration of blood clots to the pulmonary arteries in the lungs, arresting blood flow through the lungs (pulmonary embolism). Pulmonary embolism is one of the most common causes of death for hospitalized patients, and results in more than 200,000 deaths annually in the United States. The disease process in which blood clots form within a vein and subsequently migrate through the venous system to the pulmonary circulation is called venous thromboembolic disease. Numerous factors, acting independently or simultaneously, can cause clot formation within a vein and, potentially, thromboembolism: (1) damaged or irregular surfaces on the inside of the vein can lead to thrombus formation, (2) imbalances in the body's natural clotting-lytic (clot-dissolving) systems can trigger clot formation, (3) slowly-moving blood or blood passing through an area of turbulence within the vein, such as that in blood pooled in damaged leg veins, is likely to clot, and (4) the release of clotting factors into the blood from traumatized tissue is likely to trigger widespread clotting. Web site: http://www.delphion.com/details?pn=US06267776__

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Ventilation imaging using a fine particle aerosol generator Inventor(s): Farr; Stephen J. (Orinda, CA), Rubsamen; Reid M. (Oakland, CA) Assignee(s): Aradigm Corporation (hayward, Ca) Patent Number: 5,792,057 Date filed: November 26, 1997 Abstract: A method of diagnosing a patient is carried out by delivering an aerosolized dose of a radioactive formulation to a patient and making a ventilation image of radioactive material deposited in the lung. This image is compared with a separately generated image (perfusion image) taken after injecting radiolabled particles into the pulmonary arterial circulation. A diagnosis of a pulmonary embolism can be made when areas of the lung which are shown in the ventilation image are not shown within the perfusion image, indicating that air flow to that area exists, whereas a blood flow to that area has been blocked. Devices, packaging and methodology for creating aerosols are provided which allow for efficient and repeatable delivery of radioaerosols to the lungs of a patient. Devices may be plug-in units or hand-held, self-contained units which are automatically actuated at the same release point in a patient's inspiratory flow cycle. The release point is automatically determined either mechanically or, more preferably calculated by a microprocessor which receives data from a sensor making it possible to determine inspiratory flow rate and inspiratory volume. The device is loaded with a container of a radioactive formulation such as.sup.99m Tc-labelled diethylenetriamine pentaacetic acid (DTPA). Actuation of the device forces the radioactive formulation through a porous membrane of the container which membrane has pores having a diameter in the range of about 0.25 to 6.0 microns. The container includes radioactive shielding in the form of a lead coating and/or a lead surrounding packet. Excerpt(s): This invention relates generally to the field of nuclear medicine and to devices, packaging and methodology for the delivery of radioactive compounds to the lungs. More specifically, the invention relates to electromechanical devices, disposable packages and methodology for the delivery of radioactive formulation to the lungs of patients to create an image of the lungs which can be used in diagnosing the patient such as to determine the existence of lung abnormalities, including pulmonary embolism. Nuclear imaging involves introducing radioactive material into a patient, and, more specifically, into a particular tissue or tissues of that patient. After the radioactive material has been introduced, an image can be created based on the radioactive quanta emitted by the material when those particle strike a recording media, (e.g., an electronic sensory array) which is sensitive to the radioactive emissions. Images recorded electronically can be displayed on a monitor and/or transferred to film and printed for a permanent record. The process can provide life saving information. For example, tens of thousands of individuals in the United States die each year from pulmonary embolisms (PE). Detecting and diagnosing pulmonary embolisms is particularly difficult in that it often presents nonspecific clinical manifestations caused by the migration of blood clots in the deep veins of the legs (DVP) proceeding through the central venous system and into the pulmonary circulation via the right side of the heart. A clot within the pulmonary circulation results in inadequate gas exchange between the blood and the lungs, which, if sufficiently massive, can be fatal. In order to diagnose pulmonary embolism a caretaker may carry out pulmonary arterial angiography. This invasive procedure involves introducing a radiopaque dye into the pulmonary artery via percutaneous placement of a catheter into the right ventricle and through the pulmonic valve. Radiographs taken subsequent to the injection of dye

100 Pulmonary Embolism

through the catheter can be used to visualize perfusion defects associated with a pulmonary embolism. Web site: http://www.delphion.com/details?pn=US05792057__

Patent Applications on Pulmonary Embolism As of December 2000, U.S. patent applications are open to public viewing.10 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to pulmonary embolism: •

Carbon monoxide as a biomarker and therapeutic agent Inventor(s): Choi, Augustine M.; (Guilford, CT), Lee, Patty J.; (Guilford, CT), Leo, Otterbein E.; (Hamden, CT) Correspondence: Janis K. Fraser, PH.D., J.D.; Fish & Richardson P.C.; 225 Franklin Street; Boston; MA; 02110-2804; US Patent Application Number: 20020155166 Date filed: January 15, 2002 Abstract: The present invention relates to the use of carbon monoxide (CO) as a biomarker and therapeutic agent of heart, lung, liver, spleen, brain, skin and kidney diseases and other conditions and disease states including, for example, asthma, emphysema, bronchitis, adult respiratory distress syndrome, sepsis, cystic fibrosis, pneumonia, interstitial lung diseases, idiopathic pulmonary diseases, other lung diseases including primary pulmonary hypertension, secondary pulmonary hypertension, cancers, including lung, larynx and throat cancer, arthritis, wound healing, Parkinson's disease, Alzheimer's disease, peripheral vascular disease and pulmonary vascular thrombotic diseases such as pulmonary embolism. CO may be used to provide anti-inflammatory relief in patients suffering from oxidative stress and other conditions especially including sepsis and septic shock. In addition, carbon monoxide may be used as a biomarker or therapeutic agent for reducing respiratory distress in lung transplant patients and to reduce or inhibit oxidative stress and inflammation in transplant patients. Excerpt(s): This application claims priority from provisional application No. 60/127,616, filed Apr. 1, 1999. Heme oxygenase (HO) catalyzes the first and rate limiting step in the degradation of heme to yield equimolar quantities of biliverdin IXa, carbon monoxide (CO), and iron (Choi, et al., Am. J. Respir. Cell Mol. Biol. 15: 9-19; and Maines, Annu. Rev. Pharmacol. Toxicol. 37: 517-554). Three isoforms of HO exist; HO-1 is highly inducible while HO-2 and HO-3 are constitutively expressed (Choi, et al., supra, Maines, supra and McCoubrey, et al., E. J. Bioch. 247: 725-732). Although heme is the major substrate of HO-1, a variety of non-heme agents including heavy metals, cytokines, hormones, endotoxin and heat shock are also strong inducers of HO-1 expression (Choi, et al., supra, Maines, supra and Tenhunen, et al., J. Lab. Clin. Med. 75: 410-421). This diversity of HO-1 inducers has provided further support for the speculation that HO-1, besides its role in heme degradation, may also play a vital function in maintaining cellular homeostasis. Furthermore, HO-1 is highly induced by a variety of agents

10

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

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causing oxidative stress including hydrogen peroxide, glutathione depletors, UV irradiation, endotoxin and hyperoxia (Choi, et al., supra, Maines, supra and Keyse, et al., Proc. Natl. Acad. Sci. USA. 86: 99-103). One interpretation of this finding is that HO-1 can serve as a key biological molecule in the adaptation and/or defense against oxidative stress (Choi, et al., supra, Lee, et al., Proc Natl Acad Sci USA 93: 10393-10398; Otterbein, et al., Am. J. J. Respir. Cell Mol. Biol. 13: 595-601; Poss, et al., Proc. Natl. Acad. Sci. USA. 94: 10925-10930; Vile, et al., Proc. Natl. Acad. Sci. 91: 2607-2610; Abraham, et al., Proc. Natl. Acad. Sci. USA. 92: 6798-6802; and Vile and Tyrrell, J. Biol. Chem. 268: 14678-14681. Our laboratory and others have shown that induction of endogenous HO-1 provides protection both in vivo and in vitro against oxidative stress associated with hyperoxia and lipopolysaccharide-induced tissue injury (Lee, et al., supra, Otterbein, et al., supra and Taylor, et al., Am. J Physiol. 18: L582-L591). We have also shown that exogenous administration of HO-1 via gene transfer can provide protection against oxidant tissue injury and elicit tolerance to hyperoxic stress (Otterbein, et al., Am. J. Resp. Crit. Care Med. 157: A565 (Abstr)). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

COMPOSITION AND METHOD FOR ENHANCING FIBRINOLYSIS Inventor(s): REED, GUY L; (WINCHESTER, MA) Correspondence: Sterne, Kessler, Goldstein & Fox Pllc; 1100 New York Avenue, N.W., Suite 600; Washington; DC; 20005-3934; US Patent Application Number: 20030017147 Date filed: September 19, 1997 Abstract: The present invention relates to a novel alpha-2-antiplasmin-binding molecules and treatment for pulmonary embolism, myocardial infarction, thrombosis or stroke in a patient which comprises administering an alpha-2-antiplasmin-binding molecule capable of preventing inhibition of plasmin by endogenous alpha-2antiplasmin. The invention also relates to a treatment for pulmonary embolism, myocardial infarction, thrombosis or stroke in a patient comprising coadministrating an alpha-2-antiplasmin-binding molecule of the invention together with a thrombolytic agent. Excerpt(s): This application claims priority benefit to U.S. Appl. No. 60/026,356, filed Sep. 20, 1996, which disclosure is hereby incorporated by reference. The present invention relates to a composition and method of treatment for pulmonary embolism, myocardial infarction, thrombosis, and stroke in a patient, and more specifically to a therapy which enhances fibrinolysis comprising administering an alpha-2-antiplasminbinding molecule. The invention also relates to a treatment for enhancing fibrinolysis comprising administering an alpha-2-antiplasmin-binding molecule together with a thrombolytic agent. Venous thrombosis and pulmonary embolism are major causes of morbidity and mortality in the United States, accounting for about 270,000 hospitalizations a year (Anderson, F. A., Jr. et al., Arch. Intern. Med. 151:933-938 (1991)). In addition, it is estimated that about 50,000-200,000 patients a year die from pulmonary embolism (Lilienfeld, D. E. et al., Chest 98:1067-1072 (1990)). In surprising contrast with the mortality rate for myocardial infarction, the mortality rate for pulmonary embolism (estimated at 9.2% in treated patients) has not improved in the last 30 years (Lilienfeld, D. E. et al., Chest 98:1067-1072 (1990); Giuntini, C. et al., Chest 107:3S-9S (1995)). Moreover, survivors of venous thromboembolism are known to be at risk for recurrent thrombosis, postphlebitic syndrome, and pulmonary hypertension (Sutton, G. C. et al.,

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Br. Heart J. 39:1135-1192 (1977); Salzman, E. W. and Hirsch, J., "The Epidemiology, Pathogenesis and Natural History of Venous Thrombosis," in Hemostasis and Thrombosis: Basic Principles and Clinical Practice, Coleman, R. W. et al., eds., 3rd ed. Philadelphia, Pa. (1994), pp. 1275-1296). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Diagnostic procedures using direct injection of gaseous hyperpolarized 129Xe and associated systems and products Inventor(s): Brookeman, James R.; (Charlottesville, VA), Driehuys, Bastiaan; (Durham, NC), Fujii, Dennis; (Downingtown, PA), Hagspiel, Klaus D.; (Charlottesville, VA) Correspondence: Myers Bigel Sibley & Sajovec; PO Box 37428; Raleigh; NC; 27627; US Patent Application Number: 20020006382 Date filed: March 12, 2001 Abstract: A method of screening for pulmonary embolism uses gaseous phase polarized.sup.129Xe which is injected directly into the vasculature of a subject. The gaseous.sup.129Xe can be delivered in a controlled manner such that the gas substantially dissolves into the vasculature proximate to the injection site. Alternatively, the gas can be injected such that it remains as a gas in the bloodstream for a period of time (such as about 8-29 seconds). The injectable formulation of polarized.sup.129Xe gas is presented in small quantities of (preferably isotopically enriched) hyperpolarized.sup.129Xe and can provide high-quality vasculature MRI images or NMR spectroscopic signals with clinically useful signal resolution or intensity. One method injects the polarized.sup.129Xe as a gas into a vein and also directs another quantity of polarized gas into the subject via inhalation. In this embodiment, the perfusion uptake allows arterial signal information and the injection (venous side) allows venous signal information. The dual delivery is used to generate a combined introduction path with a more complete image signal of both the arterial and venous side of the pulmonary vasculature. In this NMR imaging method, the pulmonary embolism screening method can use the same NMR chest coil for the excitation and detection of the.sup.129Xe signals. The direct injection of small quantities of gas at particular sites along the vasculature targets specific target regions to provide increased signal intensity NMR images. The disclosure also includes related methods directed to other diagnostic vasculature regions physiological and conditions. Associated delivery and dispensing systems and methods, containers, and quantitative formulations of the polarized gas are also described. Excerpt(s): This application claims the benefit of priority from U.S. Provisional Application Serial No. 60/189,072 filed Mar. 13, 2000, the contents of which are hereby incorporated by reference as if recited in full herein. The present invention relates generally to magnetic resonance imaging ("MRI") and spectroscopy methods, and more particularly to the use of hyperpolarized.sup.129Xe in MRI and spectroscopy. MRI using hyperpolarized noble gases has been demonstrated as a viable imaging modality. See e.g., U.S. Pat. No. 5,545,396 to Albert et al. The contents of this patent are hereby incorporated by reference as if recited in full herein. Albert et al. proposed several techniques of introducing the hyperpolarized gas (either alone or in combination with another substance) to a subject, such as via direct injection, intravenous injection, and inhalation. See also Biological magnetic resonance imaging using laserpolarized.sup.129Xe, 370 Nature, pp. 199-201 (Jul. 21, 1994). Other researchers have since obtained relatively high-quality images of the lung using pulmonary ventilation of

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the lung with both hyperpolarized.sup.3He and.sup.129Xe. See J. R. MacFall, H. C. Charles, R. D. Black, H. Middleton, J. Swartz, B. Saam, B. Driehuys, C. Erickson, W. Happer, G. Cates, G. A. Johnson, and C. E. Ravin, "Human lung air spaces: Potential for MR imaging with hyperpolarized He-3, " Radiology 200, 553-558 (1996); and Mugler et al., MR Imaging and spectroscopy using hyperpolarized.sup.129Xe gas: Preliminary human results, 37 Mag. Res. Med., pp. 809-815 (1997). See also E. E. de Lange, J. P. Mugler, J. R. Brookeman, J. Knight-Scott, J. Truwit, C. D. Teates, T. M. Daniel, P. L. Bogorad, and G. D. Cates, "Lung Airspaces: MR Imaging Evaluation with Hyperpolarized Helium-3 Gas, " Radiology 210, 851-857(1999); L. F. Donnelly, J. R. MacFall, H. P. McAdams, J. M. Majure, J. Smith, D. P. Frush, P. Bogorad, H. C. Charles, and C. E. Ravin, "Cystic Fibrosis: Combined Hyperpolarized 3He-enhanced and Conventional Proton MR Imaging in the Lung--Preliminary Observations," Radiology 212 (September 1999), 885-889 (1999); H. P. McAdams, S. M. Palmer, L. F. Donnelly, H. C. Charles, V. F. Tapson, and J. R. MacFall, "Hyperpolarized 3He-Enhanced MR Imaging of Lung Transplant Recipients: Preliminary Results," AJR 173, 955-959 (1999). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Hollow guide rod for orthopaedic surgery Inventor(s): Pepper, John R.; (Cheshire, CT) Correspondence: John R. Pepper; 224 Beacon Hill Drive; Cheshire; CT; 06410; US Patent Application Number: 20040039390 Date filed: August 20, 2003 Abstract: A hollow guide rod for long bone surgery provides a pathway for fluids, as well as a pathway for information transmission of positional information from a transducer. An enlarged end will stop reamers from disengaging. High canal pressures are vented through the hollow channel, reducing the risk of pulmonary embolism. Excerpt(s): This application claims the benefits of Provisional Patent Application Ser. No. 60/404,627 filed Aug. 20, 2002 and Provisional Patent Application Ser. No. 60/414,890 filed Oct. 1, 2002. This was not federally sponsored research. Fracture fixation at the present time is done by surgically inserting a rod down the marrow canal of broken long bones. The rod allows rapid return to normal life and much improved healing times. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Modified low molecular weight heparin that inhibits clot associated coagulation factors Inventor(s): Hirsh, Jack; (Hamilton, CA), Weitz, Jeffrey; (Ancaster, CA) Correspondence: Millen, White, Zelano & Branigan, P.C.; 2200 Clarendon BLVD.; Suite 1400; Arlington; VA; 22201; US Patent Application Number: 20010046974 Date filed: June 6, 2001 Abstract: The present invention provides compositions and methods for the treatment of cardiovascular diseases. More particularly, the present invention relates to modifying thrombus formation by administering an agent which, inter alia, is capable of (1)

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inactivating fluid-phase thrombin and thrombin which is bound either to fibrin in a clot or to some other surface by catalyzing antithrombin; and (2) inhibiting thrombin generation by catalyzing factor Xa inactivation by antithrombin III (ATIII). The compositions and methods of the present invention are particularly useful for preventing thrombosis in the circuit of cardiac bypass apparatus and in patients undergoing renal dialysis, and for treating patients suffering from or at risk of suffering from thrombus-related cardiovascular conditions, such as unstable angina, acute myocardial infarction (heart attack), cerebrovascular accidents (stroke), pulmonary embolism, deep vein thrombosis, arterial thrombosis, etc. Excerpt(s): The present invention relates generally to compositions and methods for the treatment of cardiovascular disease. More particularly, the present invention relates to modifying thrombus formation and growth by administering a modified low molecular weight heparin (MLMWH) that, inter alia, is capable of (1) inactivating fluid-phase thrombin as well as thrombin which is bound either to fibrin in a clot or to some other surface by catalyzing antithrombin; and (2) inhibiting thrombin generation by catalyzing factor Xa inactivation by antithrombin III (ATIII). In addition, the present invention provides methods and compositions useful for treating cardiovascular disease. Blood coagulation is a process consisting of a complex interaction of various blood components, i.e., factors, that eventually gives rise to a fibrin clot. Generally, the blood components which participate in what has been referred to as the coagulation "cascade" are proenzymes or zymogens, i.e., enzymatically inactive proteins that are converted to proteolytic enzymes by the action of an activator which is, itself, an activated clotting factor. Coagulation factors that have undergone such a conversion are generally referred to as "activated factors," and are designated by the addition of a lower case "a" suffix (e.g., Factor VIIa). Activated Factor X ("Xa") is required to convert prothrombin to thrombin, which then converts fibrinogen to fibrin as a final stage in forming a fibrin clot. There are two systems, i.e., pathways, that promote the activation of Factor X. The "intrinsic pathway" refers to those reactions that lead to thrombin formation through utilization of factors present only in plasma. A series of protease-mediated reactions ultimately generates Factor IXa that, in conjunction with Factor VIIIa, cleaves Factor X into Xa. An identical proteolysis is effected by Factor VIIa and its co-factor, tissue factor, in the "extrinsic pathway" of blood coagulation. Tissue factor is a membrane bound protein and does not normally circulate in plasma. Upon vessel disruption, however, it can complex with Factor VII or Factor VIIa to catalyze Factor X activation or Factor IX activation in the presence of Ca.sup.2+ and phospholipid. While the relative importance of the two coagulation pathways in hemostasis is unclear, Factor IX activation by the Factor VIIa-tissue factor complex has, in recent years, been found to play a pivotal role in the propagation of the normal clotting response. As such, Factor IX activation in response to tissue factor exposed at sites of vascular injury can contribute to thrombosis, a pathological manifestation of the clotting cascade in blood vessels. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Non-invasive device and method for the diagnosis of pulmonary vascular occlusions Inventor(s): Kline, Jeffrey A.; (Charlotte, NC) Correspondence: Hancock & Estabrook, Llp; 1500 Mony Tower I; P.O. Box 4976; Syracuse; NY; 13221-4976; US Patent Application Number: 20030060725 Date filed: September 27, 2001

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Abstract: The invention involves a device and method for ascertaining the functioning of the respiratory system and determining whether a pulmonary embolism is present. The device comprises an apparatus containing sensors for measuring the oxygen and carbon dioxide concentrations as well as the volume of air inhaled and exhaled by a patient. From this data, a processor computes the ratio of carbon dioxide to oxygen for the volume of expired air and displays the results on a screen. By comparing the results to predetermined normal values, an accurate determination can be made regarding the presence of a pulmonary embolism. Excerpt(s): The present invention relates generally to vascular occlusions of the respiratory system, and more particularly to non-invasive devices and methods for the diagnosis of a pulmonary embolism and related disorders. A pulmonary embolism occurs when an embolus become lodged in lung arteries, thus blocking blood flow to lung tissue. An embolus is usually a blood clot, known as a thrombus, but may also comprise fat, amniotic fluid, bone marrow, tumor fragments, or even air bubbles that block a blood vessel. Unless treated promptly, a pulmonary embolism can be fatal. In the United States alone, around 600,000 cases occur annually, 10 percent of which result in death. The detection of a pulmonary embolism is extremely difficult because signs and symptoms can easily be attributed to other conditions and symptoms may vary depending on the severity of the occurrence. Frequently, a pulmonary embolism is confused with a heart attack, pneumonia, hyperventilation, congestive heart failure or a panic attack. In other cases, there may be no symptoms at all. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Prevention and treatment of deep venous thrombosis Inventor(s): Herz, Frederick Stephan Michael; (Warrington, PA), Reichle, Frederick A.; (Warrington, PA) Correspondence: Frederick S.M. Herz; PO Box 67; Warrington; PA; 18976; US Patent Application Number: 20030069528 Date filed: September 23, 2002 Abstract: Deep venous thombosis with the attendant risk of pulmonary embolism and post phlebitic syndrome is a frequent complication in older patients who have undergone surgery, suffered trauma or who have serious illness such as malignancy or sepsis. In any category patients who are 40 years of age or older are considered to be at greatest risk. Deep vein thrombi vary from a few millimeters in length to long tubular masses that partially or completely fill the deep main veins of the leg. These thrombi start as small nidi and initially grow in size by deposition of successive red and white layers. The white layers are rich in platelets and neutrophils interspersed with fibrin while the red layers contain most erythrocytes entrapped in fibrin (Hume et al, p. 26-30). Beyond a certain stage of growth venous thrombi become mostly red, resembling clotted blood, i.e., the bulk of a clinically significant thrombus is composed mostly of erythrocytes entrapped in fibrin. Thus, platelets, neutrophils and especially blood coagulation all contribute to formation of thrombi in deep leg veins. Both initiation and propagation of thrombi depend on processes that are necessary for defense of the body against trauma and infection. Platelet activation (and accumulation) and blood coagulation are necessary to stop the loss of blood from disrupted blood vessels. Neutrophil response to stimulation is essential for defense of the body against infection.Thus, initiation and propagation of DVT might be considered to represent an undesirably large response of normal defense mechanisms in the deep veins of the leg.

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Approaches to preventing DVT must be based on a realization that neither of these processes can be completely inhibited throughout the body for more than a brief time without serious risk of bleeding or infection. Thus it is obviously desirable to inhibit thrombotic processes locally rather than systemically. To do this it will be necessary to obtain higher levels of antithrombotic drugs in the deep veins of the legs than in the systemic circulation. The present patent application proposes devices and methods that will make this possible for the first time. The claims can be considered in two categories. The first is devices necessary to achieve such delivery. The second is a method for delivery of a high level of antithrombotic drugs. Excerpt(s): Deep venous thrombosis with the attendant risk of pulmonary embolism and post phlebitic syndrome is a frequent complication in older patients who have undergone surgery, suffered trauma or who have serious illness such as malignancy or sepsis. In any category patients who are 40 years of age or older are considered to be at greatest risk. Also the longer the period of immobilization the greater the risk of DVT. Other factors that have been reported to contribute to development of DVT are obesity, prior history of DVT and smoking. While none of these factors alone or in combination will identify individual patients who will develop DVT, the incidence of DVT during the postoperative or post-traumatic period does correlate with the condition. DVT has three major risks for the patient, two acute and one delayed. The acute problems are leg swelling, pain and tenderness and the risk of pulmonary embolism. In pulmonary embolism part of the thrombus breaks away and is carried to the lung where it can block a pulmonary artery causing respiratory distress in proportion to the amount of blockage, i.e., to the size of the embolus. Large emboli that block both pulmonary arteries cause immediate death. The delayed problem is the post phlebitic syndrome in which there is lower extremity pain or cramps at rest, leg edema, skin changes and skin breakdown causing chronic ulcers of the lower extremity. Clinicians have long known that the post phlebitic syndrome develops in a large percentage of patients who have DVT, especially those having extensive thrombus formation. Objective studies have shown that 1-10 years following the occurrence of DVT as much as 80% of patients will have both symptoms and abnormal venous hemodynamics (Lindner et al, 1986; Markel et at, 1992). While the post phlebitic syndrome is less dramatic than a major pulmonary embolus, it is a serious condition for the patients, resulting in much discomfort and expense. In some patients groups DVT and pulmonary embolism are major causes of morbidity and mortality. Thromboembolism is a major cause of morbidity and mortality in patients with spinal cord injury. The prevalence of DVT has been reported to range from 47% (Merli et al, 1988) to 78% (Green et al, 1982). Of these 1 to 2% will die of pulmonary embolism (Green, 1991). Thrombosis usually occurs 1 to 3 weeks after injury, with a peak between days 7 and 9. The incidence of thromboembolic complications in patients undergoing surgery for fractured hip is high, ranging from about 40-60% (Powers et al, 1989; Fordyce and Ling, 1992; Turpie, 1991; Levine et al, 1991; Hull et al, 1990). In patients undergoing knee arthroplasty the incidence of DVT ranges from about 50% to 85% (Stulberg et al, 1984; Leclerc et al, 1992; Wilson et al, 1992). In gynecologic malignancy the incidence of DVT was 35% (Clarke-Person et al, 1984). The incidence of DVT in patients undergoing elective general abdominal surgery was about 9% in those without malignancy and about 11% in those with malignancies (Bergqvist et al, Seminars in Thromb & Hemost 16 Suppl 19-24, 1990). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Thromboxane inhibitors, compositions and methods of use Inventor(s): Tejada, Inigo Saenz de; (Madrid, ES) Correspondence: Edward D Grieff; Hale & Dorr Llp; 1455 Pennsylvania Ave, NW; Washington; DC; 20004; US Patent Application Number: 20030050305 Date filed: November 1, 2002 Abstract: The present invention describes methods for treating or preventing sexual dysfunctions in males and females, and for enhancing sexual responses in males and females by administering a therapeutically effective amount of at least one thromboxane inhibitor, and, optionally, at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase, and/or at least one vasoactive agent. The male or female may preferably be diabetic. The present invention also provides novel compositions comprising at least one thromboxane inhibitor, and, at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase, and, optionally, at least one therapeutic agent, such as, vasoactive agents, nonsteroidal antiinflanmmatory compounds (NSAIDs), selective cyclooxygenase-2 (COX-2) inhibitors, anticoagulants, angiotensin converting enzymes (ACE) inhibitors, angiotensin II receptor antagonists, renin inhibitors, and mixtures thereof. The present invention also provides methods for treating or preventing ischemic heart disorders, myocardial infarction, angina pectoris, stroke, migraine, cerebral hemorrhage, cardiac fatalities, transient ischaemic attacks, complications following organ transplants, coronary artery bypasses, angioplasty, endarterectomy, atherosclerosis, pulmonary embolism, bronchial asthma, bronchitis, pneumonia, circulatory shock of various organs, nephritis, graft rejection, cancerous metastases, pregnancy-induced hypertension, preeclampsia, eclampsia, thrombotic and thromboembolic disorders, intrauterine growth, gastrointestinal disorders, renal diseases and disorders, disorders resulting from elevated uric acid levels and dysmenorrhea, and for inhibiting platelet aggregation or platelet adhesion or relaxing smooth muscles. Excerpt(s): This application is a continuation of PCT/US01/16318 filed May 22, 2001, which claims priority to U.S. Provisional Application No. 60/205,536 filed May 22, 2000. The present invention describes methods for treating or preventing sexual dysfunctions in males and females, and for enhancing sexual responses in males and females by administering a therapeutically effective amount of at least one thromboxaiie inhibitor, and, optionally, at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase, and/or at least one vasoactive agent. The male or female may preferably be diabetic. The present invention also provides novel compositions comprising at least one thromboxane inhibitor, and, at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase, and, optionally, at least one therapeutic agent, such as, vasoactive agents, nonsteroidal antiinflammatory compounds (NSAIDs), selective cyclooxygenase-2 (COX-2) inhibitors, anticoagulaits, angiotensin converting enzymes (ACE) inhibitors, angiotensin II receptor antagonists, renin inhibitors, and mixtures thereof. The present invention also provides methods for treating or preventing ischemic heart disorders, myocardial infarction,

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angina pectoris, stroke, migraine, cerebral hemorrhage, cardiac fatalities, transient ischaemic attacks, complications following organ transplants, coronary artery bypasses, angioplasty, endarterectomy, atherosclerosis, pulmonary embolism, bronchial asthma, bronchitis, pneumonia, circulatory shock of various organs, nephritis, graft rejection, cancerous metastases, pregnancy-induced hypertension, preeclampsia, eclampsia, thrombotic and thromboembolic disorders, intrauterine growth, gastrointestinal disorders, renal diseases and disorders, disorders resulting from elevated uric acid levels and dysmenorrhea, and for inhibiting platelet aggregation or platelet adhesion or relaxing smooth muscles. Adequate sexual function is a complex interaction of hormonal events and psychosocial relationships. There are four stages to sexual response as described in the International Journal of Gynecology & Obstetrics, 51(3):265277 (1995). The first stage of sexual response is desire. The second stage of sexual response is arousal. Both physical and emotional stimulation may lead to breast and genital vasodilation and clitoral engorgement (vasocongestion). In the female, dilation and engorgement of the blood vessels in the labia and tissue surrounding the vagina produce the "orgasmic platform," an area at the distal third of the vagina where blood becomes sequestered. Localized perivaginal swelling and vaginal lubrication make up the changes in this stage of sexual response. Subsequently, ballooning of the proximal portion of the vagina and elevation of the uterus occurs. In the male, vasodilation of the cavernosal arteries and closure of the venous channels that drain the penis produce an erection. The third stage of sexual response is orgasm, while the fourth stage is resolution. Interruption or absence of any of the stages of the sexual response cycle can result in sexual dysfunction. One study found that 35% of males and 42% of females reported some form of sexual dysfunction. Read et al, J. Public Health Med., 19(4):387391 (1997). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Keeping Current In order to stay informed about patents and patent applications dealing with pulmonary embolism, 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 “pulmonary embolism” (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 pulmonary embolism. You can also use this procedure to view pending patent applications concerning pulmonary embolism. 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. BOOKS ON PULMONARY EMBOLISM Overview This chapter provides bibliographic book references relating to pulmonary embolism. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on pulmonary embolism include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.

Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “pulmonary embolism” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “pulmonary embolism” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “pulmonary embolism” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

Acute Pulmonary Embolism: A Challenge for Hemostasiology by A. Geibel (Editor), et al; ISBN: 3798511675; http://www.amazon.com/exec/obidos/ASIN/3798511675/icongroupinterna

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Diagnosis and Management of Pulmonary Embolism (CD-ROM) by Stavros Konstantinides, et al; ISBN: 1588900991; http://www.amazon.com/exec/obidos/ASIN/1588900991/icongroupinterna

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Diagnosis and Treatment of Deep Venous Thrombosis and Pulmonary Embolism by Jodi B. Segal; ISBN: 1587630796; http://www.amazon.com/exec/obidos/ASIN/1587630796/icongroupinterna

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Prevention of Venous Thrombosis and Pulmonary Embolism by J.G. Sharnoff; ISBN: 0852002955; http://www.amazon.com/exec/obidos/ASIN/0852002955/icongroupinterna

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Pulmonary emboli; ISBN: 0808909045; http://www.amazon.com/exec/obidos/ASIN/0808909045/icongroupinterna

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Pulmonary embolism by Walter G. Wolfe; ISBN: 0721695841; http://www.amazon.com/exec/obidos/ASIN/0721695841/icongroupinterna

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Pulmonary Embolism by M. Morpurgo (Editor); ISBN: 0824791789; http://www.amazon.com/exec/obidos/ASIN/0824791789/icongroupinterna

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Pulmonary Embolism by T. Nakano (Editor), Samuel Z. Goldhaber (Editor); ISBN: 4431702385; http://www.amazon.com/exec/obidos/ASIN/4431702385/icongroupinterna

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Pulmonary Embolism by Paul D. Stein; ISBN: 0683079964; http://www.amazon.com/exec/obidos/ASIN/0683079964/icongroupinterna

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Pulmonary Embolism by J. Widimsky (Editor); ISBN: 380550487X; http://www.amazon.com/exec/obidos/ASIN/380550487X/icongroupinterna

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Pulmonary Embolism and Deep Venous Thrombosis by Samuel Z. Goldhaber; ISBN: 0721641512; http://www.amazon.com/exec/obidos/ASIN/0721641512/icongroupinterna

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Pulmonary Embolism: Epidemiology, Diagnosis and Treatment by Matthijs Oudkerk, et al; ISBN: 0632042230; http://www.amazon.com/exec/obidos/ASIN/0632042230/icongroupinterna

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Pulmonary thromboembolism; ISBN: 0815159781; http://www.amazon.com/exec/obidos/ASIN/0815159781/icongroupinterna

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The Diagnosis of Deep Vein Thrombosis and Pulmonary Embolism (Proceedings of a Symposium, Mexico City, April 1994) by G. Agnelli (Editor), et al; ISBN: 3805561164; http://www.amazon.com/exec/obidos/ASIN/3805561164/icongroupinterna

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Venous Thrombosis and Pulmonary Embolism by Michael Hume, et al; ISBN: 0674933206; http://www.amazon.com/exec/obidos/ASIN/0674933206/icongroupinterna

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Venous Thrombosis and Pulmonary Embolism: Diagnostic Methods (Methods in Hematology, Vol 18) by Jack Hirsh (Editor); ISBN: 0443033110; http://www.amazon.com/exec/obidos/ASIN/0443033110/icongroupinterna

Chapters on Pulmonary Embolism In order to find chapters that specifically relate to pulmonary embolism, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and pulmonary embolism using the “Detailed Search” option. Go to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Book Chapter.” Type “pulmonary embolism” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on pulmonary embolism: •

Priapism Source: in Lechtenberg, R.; Ohl, D.A. Sexual Dysfunction. Malvern, PA: Lea and Febiger. 1994. p. 128-150.

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Contact: Available from Lea and Febiger. P.O. Box 3024, 200 Chester Field Parkway, Malvern, PA 19355-9725. (215) 251-2230. PRICE: $69.50; plus shipping and handling. ISBN: 0812114965. Summary: This chapter, from a book about the neurologic, urologic, and gynecologic aspects of sexual dysfunction, discusses priapism, which is persistent and often painful erection of the penis that develops independently of sexual arousal. Topics include the pathophysiology of priapism; classification; low-flow priapism; the importance of prompt therapy; etiology, including intracavernosal pharmacotherapy of impotence, sickle cell anemia, systemic medications, anesthesia, coagulopathies, hemodialysis, trauma, hyperalimentation, neoplasms and cancer, vascular surgery for impotence, and neurologic conditions; treatment modalities, including nonsurgical therapy, amyl nitrate, anesthesia, aspiration of the corpus cavernosum, fibrinolytic therapy, intracavernosal adrenergic agonists, and surgical therapy; the results of shunting procedures; embolization; management following detumescence therapy; complications of priapism and treatment, including pulmonary embolism, urethrocavernous fistula, and penile gangrene; and the treatment of postpriapism impotence. The chapter includes a strategy for the treatment of priapism. 4 figures. 1 table. 110 references.

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CHAPTER 6. PERIODICALS AND NEWS ON PULMONARY EMBOLISM Overview In this chapter, we suggest a number of news sources and present various periodicals that cover pulmonary embolism.

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

Thrombolysis improves survival in patients with pulmonary embolism Source: Reuters Industry Breifing Date: January 01, 2003

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Alteplase added to heparin improves outcome in pulmonary embolism Source: Reuters Industry Breifing Date: October 09, 2002

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Spiral CT inadequate for diagnosis of pulmonary embolism in critically ill surgical patients Source: Reuters Medical News Date: May 29, 2001

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D-dimer, alveolar dead-space assays rapidly rule out pulmonary embolism in ED Source: Reuters Industry Breifing Date: February 15, 2001

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Spiral computed tomography effectively rules out pulmonary embolism Source: Reuters Medical News Date: February 09, 2001

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Clinical score aids pulmonary embolism diagnosis in emergency department Source: Reuters Medical News Date: January 09, 2001

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Venous stasis syndrome more likely after DVT than after pulmonary embolism alone Source: Reuters Medical News Date: December 13, 2000

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Pulmonary embolism presentation often atypical in elderly Source: Reuters Medical News Date: August 18, 2000

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New rotational pigtail catheter effective for fragmentation of pulmonary emboli Source: Reuters Industry Breifing Date: August 04, 2000

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Oral contraceptive users at higher risk of fatal pulmonary embolism Source: Reuters Industry Breifing Date: June 16, 2000

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Pulmonary embolism not ruled out by lower extremity venous ultrasound Source: Reuters Medical News Date: June 08, 2000

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Aspirin prevents perioperative pulmonary embolism, DVT Source: Reuters Medical News Date: April 14, 2000

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Silent pulmonary embolism common in patients with proximal DVT Source: Reuters Medical News Date: January 27, 2000

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High prevalence of pulmonary embolism and DVT reported Source: Reuters Medical News Date: October 14, 1999

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Bedside test can detect pulmonary embolism in critically ill patients Source: Reuters Medical News Date: August 13, 1999

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Double bolus of reteplase suitable intervention for massive pulmonary embolism Source: Reuters Medical News Date: August 05, 1999

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Pulmonary embolism uncommon but difficult to diagnosis in HIV-infected patients Source: Reuters Medical News Date: March 19, 1999

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Femoral vein stick risky for tPA recipients with pulmonary embolism Source: Reuters Medical News Date: January 18, 1999

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ASH Report: Postop pulmonary embolism risk in elderly cut by calcium blockers Source: Reuters Medical News Date: May 15, 1998

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Aggressive Cancer Screening Not Warranted After Primary Venous Thrombosis Or Pulmonary Embolism Source: Reuters Medical News Date: April 23, 1998

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Streptokinase As Effective As Alteplase For Pulmonary Embolism Source: Reuters Medical News Date: April 08, 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 “pulmonary embolism” (or synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests.

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Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “pulmonary embolism” (or synonyms). If you know the name of a company that is relevant to pulmonary embolism, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/. BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “pulmonary embolism” (or synonyms).

Academic Periodicals covering Pulmonary Embolism Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to pulmonary embolism. In addition to these sources, you can search for articles covering pulmonary embolism 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 7. 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 pulmonary embolism. 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 pulmonary embolism. 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 pulmonary embolism: Anticoagulants •

Systemic - U.S. Brands: Coumadin; Miradon http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202050.html

Ardeparin •

Systemic - U.S. Brands: Normiflo http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203494.html

Dalteparin •

Systemic - U.S. Brands: Fragmin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202910.html

Danaparoid •

Systemic - U.S. Brands: Orgaran http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203583.html

Heparin •

Systemic - U.S. Brands: Calciparine; Liquaemin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202280.html

Pegademase •

Systemic - U.S. Brands: Adagen http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202443.html

Pegaspargase •

Systemic - U.S. Brands: Oncaspar http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203543.html

Peginterferon Alfa-2B •

Systemic - U.S. Brands: PEG-Intron http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500287.html

Pemirolast •

Ophthalmic - U.S. Brands: Alamast http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500115.html

Pemoline •

Systemic - U.S. Brands: Cylert http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202444.html

Penciclovir •

Topical - U.S. Brands: Denavir http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203495.html

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Penicillamine •

Systemic - U.S. Brands: Cuprimine; Depen http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202445.html

Penicillins •

Systemic - U.S. Brands: Amoxil; Bactocill; Beepen-VK; Betapen-VK; Bicillin L-A; Cloxapen; Crysticillin 300 A.S.; Dycill; Dynapen; Geocillin; Geopen; Ledercillin VK; Mezlin; Nafcil; Nallpen; Omnipen; Omnipen-N; Pathocil; Pen Vee K; Pentids; Permapen; Pfizerpen; Pfizerpen-AS http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202446.html

Penicillins and Beta-Lactamase Inhibitors •

Systemic - U.S. Brands: Augmentin; Timentin; Unasyn; Zosyn http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202705.html

Pentagastrin •

Diagnostic - U.S. Brands: Peptavlon http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202447.html

Pentamidine •

Inhalation - U.S. Brands: NebuPent http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202448.html

Pentosan •

Systemic - U.S. Brands: Elmiron http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203359.html

Pentostatin •

Systemic - U.S. Brands: Nipent http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202650.html

Pentoxifylline •

Systemic - U.S. Brands: Trental http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202450.html

Pergolide •

Systemic - U.S. Brands: Permax http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202451.html

Perphenazine and Amitriptyline •

Systemic - U.S. Brands: Etrafon; Etrafon-A; Etrafon-Forte; Triavil http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202453.html

Thrombolytic Agents •

Systemic - U.S. Brands: Abbokinase; Abbokinase Open-Cath; Activase; Eminase; Retavase; Streptase http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202565.html

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Tinzaparin •

Systemic - U.S. Brands: Innohep http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500175.html

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

Mosby’s Drug Consult Mosby’s Drug Consult database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/. PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee.

Researching Orphan Drugs Although the list of orphan drugs is revised on a daily basis, you can quickly research orphan drugs that might be applicable to pulmonary embolism by using the database managed by the National Organization for Rare Disorders, Inc. (NORD), at http://www.rarediseases.org/. Scroll down the page, and on the left toolbar, click on “Orphan Drug Designation Database.” On this page (http://www.rarediseases.org/search/noddsearch.html), type “pulmonary embolism” (or synonyms) into the search box, and click “Submit Query.” When you receive your results, note that not all of the drugs may be relevant, as some may have been withdrawn from orphan status. Write down or print out the name of each drug and the relevant contact information. From there, visit the Pharmacopeia Web site and type the name of each orphan drug into the search box at http://www.nlm.nih.gov/medlineplus/druginformation.html. You may need to contact the sponsor or NORD for further information.

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NORD conducts “early access programs for investigational new drugs (IND) under the Food and Drug Administration’s (FDA’s) approval ‘Treatment INDs’ programs which allow for a limited number of individuals to receive investigational drugs before FDA marketing approval.” If the orphan product about which you are seeking information is approved for marketing, information on side effects can be found on the product’s label. If the product is not approved, you may need to contact the sponsor. The following is a list of orphan drugs currently listed in the NORD Orphan Drug Designation Database for pulmonary embolism: •

Reviparin Sodium (trade name: Clivarine) http://www.rarediseases.org/nord/search/nodd_full?code=1124

•

Protein C concentrate (trade name: Protein C Concentrate (human) Vapor Heated, Immuno) http://www.rarediseases.org/nord/search/nodd_full?code=439

•

Antithrombin III (human) (trade name: Thrombate III) http://www.rarediseases.org/nord/search/nodd_full?code=658

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

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APPENDICES

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

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

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

•

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

•

National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html

•

National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25

•

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

•

National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm

•

National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375

•

National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/

11

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

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•

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

•

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

•

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

•

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

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

•

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

•

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

•

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

•

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

•

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

12

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

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•

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

•

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

The NLM Gateway14 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.15 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “pulmonary embolism” (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 25231 319 415 32 54 26051

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

14

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

15

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

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

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

Physician Resources 129

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

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

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

•

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

19 Adapted 20

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

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

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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on pulmonary embolism can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internet-based services that post them.

Patient Guideline Sources The remainder of this chapter directs you to sources which either publish or can help you find additional guidelines on topics related to pulmonary embolism. 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 pulmonary embolism. 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 “pulmonary embolism”:

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Pulmonary Embolism

Circulatory Disorders http://www.nlm.nih.gov/medlineplus/circulatorydisorders.html Pulmonary Embolism http://www.nlm.nih.gov/medlineplus/pulmonaryembolism.html Pulmonary Fibrosis http://www.nlm.nih.gov/medlineplus/pulmonaryfibrosis.html Pulmonary Hypertension http://www.nlm.nih.gov/medlineplus/pulmonaryhypertension.html Respiratory Diseases http://www.nlm.nih.gov/medlineplus/respiratorydiseases.html Thrombophlebitis http://www.nlm.nih.gov/medlineplus/thrombophlebitis.html

Within the health topic page dedicated to pulmonary embolism, the following was listed: •

General/Overviews JAMA Patient Page: Pulmonary Embolism Source: American Medical Association http://www.medem.com/medlb/article_detaillb.cfm?article_ID=ZZZDQHMZUIC &sub_cat=575 Pulmonary Embolism Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=DS00429 Pulmonary Embolism and Deep Vein Thrombosis http://circ.ahajournals.org/cgi/reprint/106/12/1436.pdf

•

Diagnosis/Symptoms Cough Source: American Academy of Family Physicians http://familydoctor.org/516.xml Radiography -- Chest (Chest X-ray) Source: American College of Radiology, Radiological Society of North America http://www.radiologyinfo.org/content/chest_radiography.htm Shortness of Breath: Self-Care Flowchart Source: American Academy of Family Physicians http://familydoctor.org/521.xml Vascular Diseases Diagnosis Source: Society of Interventional Radiology http://www.sirweb.org/patPub/vascularDiagnosis.shtml

•

Treatment Pulmonary Thromboendarterectomy for Chronic Pulmonary Embolism Source: Society of Thoracic Surgeons http://www.ctsnet.org/doc/5595

Patient Resources 133

Treatment of Blood Clots http://circ.ahajournals.org/cgi/reprint/106/20/e138.pdf Vascular Diseases Treatments Source: Society of Interventional Radiology http://www.sirweb.org/patPub/vascularTreatments.shtml What Are Anticoagulants and Antiplatelet Agents? Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=84 •

Specific Conditions/Aspects Flight-Related Deep Vein Thrombosis (DVT) - “Economy Class Syndrome” Source: National Aeronautics and Space Administration http://ohp.nasa.gov/alerts/dvt.html New Perspective on Deep Vein Thrombosis Source: American Venous Forum http://www.dvt-info.com/education/newpers.html

•

Organizations National Heart, Lung, and Blood Institute http://www.nhlbi.nih.gov/

•

Prevention/Screening Aspirin: From Pain Relief to Preventive Medicine Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=HQ00269

•

Research Comparison of Two Methods of Starting the Anticoagulant Drug Warfarin Source: American College of Physicians http://www.annals.org/cgi/content/full/138/9/I-50 Consequences of Serious Bleeding Complications from Warfarin Source: American College of Physicians http://www.annals.org/cgi/content/full/139/11/I-22 Detecting Clots in the Lungs Source: American College of Physicians http://www.annals.org/cgi/content/full/138/4/I-58 Excluding Pulmonary Embolism Safely Source: American College of Physicians http://www.annals.org/cgi/content/full/138/12/I-18 How Long Should Blood Thinners Be Given to Patients Who Have Had a Pulmonary Embolism? Source: American College of Physicians http://www.annals.org/cgi/content/full/139/1/I-51

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Low Dose Warfarin Prevents Recurrence of Blood Clots - NHLBI Stops Study Source: National Heart, Lung, and Blood Institute http://www.nih.gov/news/pr/feb2003/nhlbi-24.htm Treatment of Pulmonary Embolism Source: American College of Physicians http://www.annals.org/cgi/content/full/140/3/I-43 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 National Guideline Clearinghouse™ The National Guideline Clearinghouse™ offers hundreds of evidence-based clinical practice guidelines published in the United States and other countries. You can search this site located at http://www.guideline.gov/ by using the keyword “pulmonary embolism” (or synonyms). The following was recently posted: •

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

•

1999 update: ACC/AHA guidelines for the management of patients with acute myocardial infarction. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Acute Myocardial Infar Source: American College of Cardiology Foundation - Medical Specialty Society; 1996 November 1 (revised 1999 Sep); 22 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2006&nbr=1232&a mp;string=pulmonary+AND+embolism

•

A guideline for the management of heart failure Source: National Heart Foundation of New Zealand - Disease Specific Society; 1996 (revised 2001 Dec); 30 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3309&nbr=2535&a mp;string=pulmonary+AND+thromboembolism

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•

AACE medical guidelines for clinical practice for management of menopause Source: American Association of Clinical Endocrinologists - Medical Specialty Society; 1999 Nov-December; 13 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2138&nbr=1364&a mp;string=pulmonary+AND+embolism

•

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

•

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

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ACR Appropriateness Criteriatm for acute chest pain--suspected pulmonary embolism Source: American College of Radiology - Medical Specialty Society; 1995 (revised 1999); 7 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2381&nbr=1607&a mp;string=pulmonary+AND+embolism

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ACR Appropriateness Criteriatm for suspected lower extremity deep vein thrombosis Source: American College of Radiology - Medical Specialty Society; 1995 (revised 1999); 5 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2386&nbr=1612&a mp;string=pulmonary+AND+embolism

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Adjuvant therapy for breast cancer Source: National Cancer Institute - Federal Government Agency [U.S.]; 2000 November 3; 24 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2715&nbr=1941&a mp;string=pulmonary+AND+thromboembolism

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Altered mental states Source: American Health Care Association - Professional Association; 1998 (reviewed 2003); 20 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1804&nbr=1030&a mp;string=pulmonary+AND+embolism

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

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Antithrombotic agents in coronary artery disease. In: Sixth ACCP Consensus Conference on Antithrombotic Therapy Source: American College of Chest Physicians - Medical Specialty Society; 2001 January; 25 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2729&nbr=1955&a mp;string=pulmonary+AND+embolism

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

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Antithrombotic therapy for venous thromboembolic disease. In: Sixth ACCP Consensus Conference on Antithrombotic Therapy Source: American College of Chest Physicians - Medical Specialty Society; 2001 January; 18 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2725&nbr=1951&a mp;string=pulmonary+AND+embolism

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Antithrombotic therapy in children. In: Sixth ACCP Consensus Conference on Antithrombotic Therapy Source: American College of Chest Physicians - Medical Specialty Society; 2001 January; 27 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2735&nbr=1961&a mp;string=pulmonary+AND+thromboembolism

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Antithrombotic therapy in valvular heart disease. In: Sixth ACCP Consensus Conference on Antithrombotic Therapy Source: American College of Chest Physicians - Medical Specialty Society; 2001 January; 13 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2727&nbr=1953&a mp;string=pulmonary+AND+embolism

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

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Breast cancer treatment Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1996 September (revised 2003 Jan); 45 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3670&nbr=2896&a mp;string=pulmonary+AND+embolism

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Capnography/capnometry during mechanical ventilation: 2003 revision and update Source: American Association for Respiratory Care - Professional Association; 1995 December (revised 2003); 6 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3754&nbr=2980&a mp;string=pulmonary+AND+embolism

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Chemoprevention of breast cancer: recommendations and rationale Source: United States Preventive Services Task Force - Independent Expert Panel; 2002 July; 24 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3229&nbr=2455&a mp;string=pulmonary+AND+embolism

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

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Clinical policy: critical issues in the evaluation and management of adult patients presenting with suspected lower-extremity deep venous thrombosis Source: American College of Emergency Physicians - Medical Specialty Society; 2003 July; 12 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3867&nbr=3077&a mp;string=pulmonary+AND+embolism

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Clinical policy: critical issues in the evaluation and management of adult patients presenting with suspected pulmonary embolism Source: American College of Emergency Physicians - Medical Specialty Society; 2003 February; 14 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3692&nbr=2918&a mp;string=pulmonary+AND+embolism

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Clinical practice guideline for the management of postoperative pain Source: Department of Defense - Federal Government Agency [U.S.]; 2001 July (revised 2002 May); Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3284&nbr=2510&a mp;string=pulmonary+AND+embolism

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Clinical practice guidelines for sustained neuromuscular blockade in the adult critically ill patient Source: American College of Critical Care Medicine - Professional Association; 1995 (revised 2002); 15 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3170&nbr=2396&a mp;string=pulmonary+AND+embolism

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Congestive heart failure in adults Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1997 October (revised 2002 Jan); 71 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3165&nbr=2391&a mp;string=pulmonary+AND+embolism

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Deep venous thrombosis Source: Finnish Medical Society Duodecim - Professional Association; 2001 April 30 (revised 2002 Apr 20); Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3384&nbr=2610&a mp;string=pulmonary+AND+embolism

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Delirium: strategies for assessing and treating Source: The John A. Hartford Foundation Institute for Geriatric Nursing - Academic Institution; 2003; 25 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3509&nbr=2735&a mp;string=pulmonary+AND+embolism

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

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Differential diagnosis of chest pain Source: Finnish Medical Society Duodecim - Professional Association; 2001 May 4; Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=2852&nbr=2078&a mp;string=pulmonary+AND+embolism

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Evaluation of surgery for Parkinson's disease. A report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. The Task Force on Surgery for Parkinson's Disease Source: American Academy of Neurology - Medical Specialty Society; 1999 December; 12 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2830&nbr=2056&a mp;string=pulmonary+AND+embolism

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Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease Source: National Heart, Lung, and Blood Institute (U.S.) - Federal Government Agency [U.S.]; 2001; Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=2779&nbr=2005&a mp;string=pulmonary+AND+embolism

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

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Guidelines for the prevention of intravascular catheter-related infections Source: American Academy of Pediatrics - Medical Specialty Society; 1996 (revised 2002 August 9); 36 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3387&nbr=2613&a mp;string=pulmonary+AND+embolism

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Guidelines of care for liposuction Source: American Academy of Dermatology - Medical Specialty Society; 2001 January (electronic version released to the public); 10 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2710&nbr=1936&a mp;string=pulmonary+AND+embolism

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Guidelines on diagnosis and management of acute pulmonary embolism Source: European Society of Cardiology - Medical Specialty Society; 2000 August; 36 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2592&nbr=1818&a mp;string=pulmonary+AND+embolism

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Heart failure Source: American Medical Directors Association - Professional Association; 1996 (revised 2002); 18 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3303&nbr=2529&a mp;string=pulmonary+AND+embolism

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Heparin and low molecular weight heparin. In: Sixth ACCP Consensus Conference on Antithrombotic Therapy Source: American College of Chest Physicians - Medical Specialty Society; 2001 January; 31 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2722&nbr=1948&a mp;string=pulmonary+AND+embolism

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Key clinical activities for quality asthma care: recommendations of the National Asthma Education and Prevention Program Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 2003 March 28; 8 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3734&nbr=2960&a mp;string=pulmonary+AND+embolism

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

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Management of chronic kidney disease and pre-ESRD in the primary care setting Source: Department of Defense - Federal Government Agency [U.S.]; 2000 November; Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3099&nbr=2325&a mp;string=pulmonary+AND+embolism

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

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Managing oral anticoagulant therapy. In : Sixth ACCP Consensus Conference on Antithrombotic Therapy Source: American College of Chest Physicians - Medical Specialty Society; 2001 January; 16 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2721&nbr=1947&a mp;string=pulmonary+AND+embolism

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Myocardial infarction Source: Finnish Medical Society Duodecim - Professional Association; 2001 April 30 (revised 2003 July 11); Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=4373&nbr=3295&a mp;string=pulmonary+AND+embolism

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Osteoporosis. Guide to prevention, diagnosis, and treatment Source: Brigham and Women's Hospital (Boston) - Hospital/Medical Center; 1999 (revised 2001); 11 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3430&nbr=2656&a mp;string=pulmonary+AND+embolism

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Osteoporosis: prevention and treatment Source: University of Michigan Health System - Academic Institution; 2002 March; 12 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3541&nbr=2767&a mp;string=pulmonary+AND+embolism

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Palliative treatment of cancer Source: Finnish Medical Society Duodecim - Professional Association; 2001 December 27 (revised 2003 May 30); Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=4374&nbr=3296&a mp;string=pulmonary+AND+embolism

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Perimenopausal and postmenopausal hormone replacement therapy Source: American College of Preventive Medicine - Medical Specialty Society; 1999 October; 5 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2120&nbr=1346&a mp;string=pulmonary+AND+embolism

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Physician's guide to prevention and treatment of osteoporosis Source: American Academy of Orthopaedic Surgeons - Medical Specialty Society; 1999 (revised 2003 Apr); 37 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3862&nbr=3073&a mp;string=pulmonary+AND+emboli

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Postmenopausal hormone replacement therapy for the primary prevention of chronic conditions: recommendations and rationale Source: United States Preventive Services Task Force - Independent Expert Panel; 1996 (revised 2002); 17 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3455&nbr=2681&a mp;string=pulmonary+AND+embolism

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Practice guidelines for the management of patients with histoplasmosis Source: Infectious Diseases Society of America - Medical Specialty Society; 2000 April; 8 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2668&nbr=1894&a mp;string=pulmonary+AND+emboli

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

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

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Practice parameters for the prevention of venous thromboembolism Source: American Society of Colon and Rectal Surgeons - Medical Specialty Society; 2000 August; 11 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2593&nbr=1819&a mp;string=pulmonary+AND+embolism

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Prevention and management of hip fracture in older people. A national clinical guideline Source: Scottish Intercollegiate Guidelines Network - National Government Agency [Non-U.S.]; 2002 January; 40 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3184&nbr=2410&a mp;string=pulmonary+AND+embolism

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Prevention of deep vein thrombosis Source: University of Iowa Gerontological Nursing Interventions Research Center, Research Dissemination Core - Academic Institution; 1999 June 10; 32 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1967&nbr=1193&a mp;string=pulmonary+AND+embolism

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Prevention of thromboembolism in spinal cord injury Source: Consortium for Spinal Cord Medicine - Private Nonprofit Organization; 1997 February (updated 1999 Sep); 29 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2965&nbr=2191&a mp;string=pulmonary+AND+embolism

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Prevention of venous thromboembolism. In: Sixth ACCP Consensus Conference on Antithrombotic Therapy Source: American College of Chest Physicians - Medical Specialty Society; 2001 January; 43 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2724&nbr=1950&a mp;string=pulmonary+AND+embolism

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Procedure guideline for lung scintigraphy Source: Society of Nuclear Medicine, Inc - Medical Specialty Society; 1999 February; 24 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1352&nbr=610&am p;string=pulmonary+AND+embolism

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Prophylaxis of venous thromboembolism. A national clinical guideline Source: Scottish Intercollegiate Guidelines Network - National Government Agency [Non-U.S.]; 2002 October; 47 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3485&nbr=2711&a mp;string=pulmonary+AND+embolism

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Prostate cancer Source: National Committee on Cancer Care (Singapore) - National Government Agency [Non-U.S.]; 2000 May; 49 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2836&nbr=2062&a mp;string=pulmonary+AND+embolism

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Single-breath carbon monoxide diffusing capacity, 1999 update Source: American Association for Respiratory Care - Professional Association; 1999 January; 9 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1767&nbr=993&am p;string=pulmonary+AND+thromboembolism

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

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

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Task force on the management of chest pain Source: European Society of Cardiology - Medical Specialty Society; 2002 August; 24 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3426&nbr=2652&a mp;string=pulmonary+AND+embolism

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

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Use of antithrombotic agents during pregnancy. In: Sixth ACCP Consensus Conference on Antithrombotic Therapy Source: American College of Chest Physicians - Medical Specialty Society; 2001 January; 10 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2723&nbr=1949&a mp;string=pulmonary+AND+embolism

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Venous thromboembolism Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1998 June (revised 2003 Apr); 93 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3757&nbr=2983&a mp;string=pulmonary+AND+embolism

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

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

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Pulmonary Thromboendarterectomy for Chronic Pulmonary Embolism Summary: A pulmonary embolism occurs when a blood clot lodges in the blood vessels of the lung (pulmonary arteries). The clot is called an embolus, and it most often begins as a clot in the veins of the legs. Source: Society of Thoracic Surgeons http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7735 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 pulmonary embolism. 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

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

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

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

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

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

•

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

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

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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 “pulmonary embolism” (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 “pulmonary embolism”. 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 “pulmonary embolism” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “pulmonary embolism” (or a synonym) into the search box, and click “Submit Query.”

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APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.

Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.22

Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.

Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of

22

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

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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)23: •

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

•

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

•

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

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

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

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California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html

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California: Gateway Health Library (Sutter Gould Medical Foundation)

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

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

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

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

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

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

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

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

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

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

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

23

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

Finding Medical Libraries 151

•

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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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/

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

•

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/

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

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

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

Basic Guidelines for Pulmonary Embolism CHF Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000158.htm COPD Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000091.htm DVT Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000156.htm

•

Signs & Symptoms for Pulmonary Embolism Anxiety Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003211.htm Chest pain Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003079.htm

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Cough Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003072.htm Diaphoresis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003218.htm Dyspnea Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003075.htm Fever Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003090.htm Hemoptysis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003073.htm Rales Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003323.htm Swelling Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003103.htm Syncope Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003092.htm Tachycardia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003077.htm Tachypnea Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003071.htm •

Diagnostics and Tests for Pulmonary Embolism ALT Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003473.htm Angiogram Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003327.htm Angiography Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003327.htm Arteriogram Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003327.htm Chest X-ray Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003804.htm CT Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003330.htm ECG Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003868.htm

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Echocardiogram Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003869.htm Lung scan Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003824.htm Pulmonary angiography Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003813.htm X-ray Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003337.htm •

Background Topics for Pulmonary Embolism Acute Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002215.htm

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

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

•

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

•

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

•

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

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PULMONARY EMBOLISM DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abortion: 1. The premature expulsion from the uterus of the products of conception - of the embryo, or of a nonviable fetus. The four classic symptoms, usually present in each type of abortion, are uterine contractions, uterine haemorrhage, softening and dilatation of the cervix, and presentation or expulsion of all or part of the products of conception. 2. Premature stoppage of a natural or a pathological process. [EU] Abscess: A localized, circumscribed collection of pus. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acetylgalactosamine: The N-acetyl derivative of galactosamine. [NIH] Acetylglucosamine: The N-acetyl derivative of glucosamine. [NIH] Acidity: The quality of being acid or sour; containing acid (hydrogen ions). [EU] Actin: Essential component of the cell skeleton. [NIH] Acute myeloid leukemia: AML. A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myelogenous leukemia or acute nonlymphocytic leukemia. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [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] Adrenergic Agonists: Drugs that bind to and activate adrenergic receptors. [NIH] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is

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present. [NIH] Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [EU]

Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Age-Adjusted: Summary measures of rates of morbidity or mortality in a population using statistical procedures to remove the effect of age differences in populations that are being compared. Age is probably the most important and the most common variable in determining the risk of morbidity and mortality. [NIH] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] 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] Aldehydes: Organic compounds containing a carbonyl group in the form -CHO. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alkaline: Having the reactions of an alkali. [EU] Allogeneic: Taken from different individuals of the same species. [NIH] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Alveoli: Tiny air sacs at the end of the bronchioles in the lungs. [NIH] 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

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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] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amnion: The extraembryonic membrane which contains the embryo and amniotic fluid. [NIH]

Amniotic Fluid: Amniotic cavity fluid which is produced by the amnion and fetal lungs and kidneys. [NIH] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH] Ampulla: A sac-like enlargement of a canal or duct. [NIH] Amyloid: A general term for a variety of different proteins that accumulate as extracellular fibrils of 7-10 nm and have common structural features, including a beta-pleated sheet conformation and the ability to bind such dyes as Congo red and thioflavine (Kandel, Schwartz, and Jessel, Principles of Neural Science, 3rd ed). [NIH] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Analytes: A component of a test sample the presence of which has to be demonstrated. The term "analyte" includes where appropriate formed from the analyte during the analyses. [NIH]

Anaplasia: Loss of structural differentiation and useful function of neoplastic cells. [NIH] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Aneurysm: A sac formed by the dilatation of the wall of an artery, a vein, or the heart. [NIH] Angina: Chest pain that originates in the heart. [NIH] Angina Pectoris: The symptom of paroxysmal pain consequent to myocardial ischemia usually of distinctive character, location and radiation, and provoked by a transient stressful situation during which the oxygen requirements of the myocardium exceed the capacity of the coronary circulation to supply it. [NIH] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels from surrounding tissue to a solid tumor. This is caused by the release of chemicals by the tumor. [NIH] Angiogram: An x-ray of blood vessels; the person receives an injection of dye to outline the vessels on the x-ray. [NIH] Angiography: Radiography of blood vessels after injection of a contrast medium. [NIH] Angioplasty: Endovascular reconstruction of an artery, which may include the removal of atheromatous plaque and/or the endothelial lining as well as simple dilatation. These are

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procedures performed by catheterization. When reconstruction of an artery is performed surgically, it is called endarterectomy. [NIH] Angiotensinogen: An alpha-globulin of which a fragment of 14 amino acids is converted by renin to angiotensin I, the inactive precursor of angiotensin II. It is a member of the serpin superfamily. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Ankle: That part of the lower limb directly above the foot. [NIH] Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Anterior Cerebral Artery: Artery formed by the bifurcation of the internal carotid artery. Branches of the anterior cerebral artery supply the caudate nucleus, internal capsule, putamen, septal nuclei, gyrus cinguli, and surfaces of the frontal lobe and parietal lobe. [NIH] Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibodies, Anticardiolipin: Antiphospholipid antibodies found in association with systemic lupus erythematosus (lupus erythematosus, systemic), antiphospholipid syndrome, and in a variety of other diseases as well as in healthy individuals. The antibodies are detected by solid-phase immunoassay employing the purified phospholipid antigen cardiolipin. [NIH] Antibodies, Antiphospholipid: Autoantibodies directed against phospholipids. These antibodies are characteristically found in patients with systemic lupus erythematosus, antiphospholipid syndrome, related autoimmune diseases, some non-autoimmune diseases, and also in healthy individuals. [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] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Antidote: A remedy for counteracting a poison. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Anti-infective: An agent that so acts. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH]

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Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antiphospholipid Syndrome: The presence of antibodies directed against phospholipids (antibodies, antiphospholipid). The condition is associated with a variety of diseases, notably systemic lupus erythematosus and other connective tissue diseases, thrombopenia, and arterial or venous thromboses. In pregnancy it can cause abortion. Of the phospholipids, the cardiolipins show markedly elevated levels of anticardiolipin antibodies (antibodies, anticardiolipin). Present also are high levels of lupus anticoagulant (lupus coagulation inhibitor). [NIH] Antiplasmin: A member of the serpin superfamily found in human plasma that inhibits the lysis of fibrin clots which are induced by plasminogen activator. It is a glycoprotein, molecular weight approximately 70,000 that migrates in the alpha 2 region in immunoelectrophoresis. It is the principal plasmin inactivator in blood, rapidly forming a very stable complex with plasmin. [NIH] Antipsychotic: Effective in the treatment of psychosis. Antipsychotic drugs (called also neuroleptic drugs and major tranquilizers) are a chemically diverse (including phenothiazines, thioxanthenes, butyrophenones, dibenzoxazepines, dibenzodiazepines, and diphenylbutylpiperidines) but pharmacologically similar class of drugs used to treat schizophrenic, paranoid, schizoaffective, and other psychotic disorders; acute delirium and dementia, and manic episodes (during induction of lithium therapy); to control the movement disorders associated with Huntington's chorea, Gilles de la Tourette's syndrome, and ballismus; and to treat intractable hiccups and severe nausea and vomiting. Antipsychotic agents bind to dopamine, histamine, muscarinic cholinergic, a-adrenergic, and serotonin receptors. Blockade of dopaminergic transmission in various areas is thought to be responsible for their major effects : antipsychotic action by blockade in the mesolimbic and mesocortical areas; extrapyramidal side effects (dystonia, akathisia, parkinsonism, and tardive dyskinesia) by blockade in the basal ganglia; and antiemetic effects by blockade in the chemoreceptor trigger zone of the medulla. Sedation and autonomic side effects (orthostatic hypotension, blurred vision, dry mouth, nasal congestion and constipation) are caused by blockade of histamine, cholinergic, and adrenergic receptors. [EU] Antithrombotic: Preventing or interfering with the formation of thrombi; an agent that so acts. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Aorta: The main trunk of the systemic arteries. [NIH] Aortic Valve: The valve between the left ventricle and the ascending aorta which prevents backflow into the left ventricle. [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]

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Applicability: A list of the commodities to which the candidate method can be applied as presented or with minor modifications. [NIH] Aqueous: Having to do with water. [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arteriography: A procedure to x-ray arteries. The arteries can be seen because of an injection of a dye that outlines the vessels on an x-ray. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteriosclerosis: Thickening and loss of elasticity of arterial walls. Atherosclerosis is the most common form of arteriosclerosis and involves lipid deposition and thickening of the intimal cell layers within arteries. Additional forms of arteriosclerosis involve calcification of the media of muscular arteries (Monkeberg medial calcific sclerosis) and thickening of the walls of small arteries or arterioles due to cell proliferation or hyaline deposition (arteriolosclerosis). [NIH] Arteriosus: Circle composed of anastomosing arteries derived from two long posterior ciliary and seven anterior ciliary arteries, located in the ciliary body about the root of the iris. [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] Arthroplasty: Surgical reconstruction of a joint to relieve pain or restore motion. [NIH] Aspiration: The act of inhaling. [NIH] Aspirin: A drug that reduces pain, fever, inflammation, and blood clotting. Aspirin belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is also being studied in cancer prevention. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Asymptomatic: Having no signs or symptoms of disease. [NIH] Atherectomy: Endovascular procedure in which atheromatous plaque is excised by a cutting or rotating catheter. It differs from balloon and laser angioplasty procedures which enlarge vessels by dilation but frequently do not remove much plaque. If the plaque is removed by surgical excision under general anesthesia rather than by an endovascular procedure through a catheter, it is called endarterectomy. [NIH] Atrial: Pertaining to an atrium. [EU] Atrial Fibrillation: Disorder of cardiac rhythm characterized by rapid, irregular atrial impulses and ineffective atrial contractions. [NIH] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU] Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [NIH]

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Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Bacteremia: The presence of viable bacteria circulating in the blood. Fever, chills, tachycardia, and tachypnea are common acute manifestations of bacteremia. The majority of cases are seen in already hospitalized patients, most of whom have underlying diseases or procedures which render their bloodstreams susceptible to invasion. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Basophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Bioassays: Determination of the relative effective strength of a substance (as a vitamin, hormone, or drug) by comparing its effect on a test organism with that of a standard preparation. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] 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] Biomolecular: A scientific field at the interface between advanced computing and biotechnology. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] 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

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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] Bleeding Time: Duration of blood flow after skin puncture. This test is used as a measure of capillary and platelet function. [NIH] Blood Cell Count: A count of the number of leukocytes and erythrocytes per unit volume in a sample of venous blood. A complete blood count (CBC) also includes measurement of the hemoglobin, hematocrit, and erythrocyte indices. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Coagulation Factors: Endogenous substances, usually proteins, that are involved in the blood coagulation process. [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 Substitutes: Substances that can carry oxygen to and carbon dioxide away from the tissues when introduced into the blood stream. They are used to replace hemoglobin in severe hemorrhage and also to perfuse isolated organs. The best known are perfluorocarbon emulsions and various hemoglobin solutions. [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] Body Fluids: Liquid components of living organisms. [NIH] Bolus: A single dose of drug usually injected into a blood vessel over a short period of time. Also called bolus infusion. [NIH] Bolus infusion: A single dose of drug usually injected into a blood vessel over a short period of time. Also called bolus. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone scan: A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It

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uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Breakdown: A physical, metal, or nervous collapse. [NIH] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Bronchitis: Inflammation (swelling and reddening) of the bronchi. [NIH] Bupivacaine: A widely used local anesthetic agent. [NIH] Bypass: A surgical procedure in which the doctor creates a new pathway for the flow of body fluids. [NIH] Calcification: Deposits of calcium in the tissues of the breast. Calcification in the breast can be seen on a mammogram, but cannot be detected by touch. There are two types of breast calcification, macrocalcification and microcalcification. Macrocalcifications are large deposits and are usually not related to cancer. Microcalcifications are specks of calcium that may be found in an area of rapidly dividing cells. Many microcalcifications clustered together may be a sign of cancer. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calcium blocker: A drug used to relax the blood vessel and heart muscle, causing pressure inside blood vessels to drop. It also can regulate heart rhythm. [NIH] Calpain: Cysteine proteinase found in many tissues. Hydrolyzes a variety of endogenous proteins including neuropeptides, cytoskeletal proteins, proteins from smooth muscle, cardiac muscle, liver, platelets and erythrocytes. Two subclasses having high and low calcium sensitivity are known. Removes Z-discs and M-lines from myofibrils. Activates phosphorylase kinase and cyclic nucleotide-independent protein kinase. [NIH] 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] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH]

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Carcinogenesis: The process by which normal cells are transformed into cancer cells. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]

Cardiac: Having to do with the heart. [NIH] Cardiac arrest: A sudden stop of heart function. [NIH] Cardiac Output: The volume of blood passing through the heart per unit of time. It is usually expressed as liters (volume) per minute so as not to be confused with stroke volume (volume per beat). [NIH] Cardiolipins: Acidic phospholipids composed of two molecules of phosphatidic acid covalently linked to a molecule of glycerol. They occur primarily in mitochondrial inner membranes and in bacterial plasma membranes. They are the main antigenic components of the Wassermann-type antigen that is used in nontreponemal syphilis serodiagnosis. [NIH] Cardiology: The study of the heart, its physiology, and its functions. [NIH] Cardiopulmonary: Having to do with the heart and lungs. [NIH] Cardiopulmonary Bypass: Diversion of the flow of blood from the entrance of the right atrium directly to the aorta (or femoral artery) via an oxygenator thus bypassing both the heart and lungs. [NIH] Cardiopulmonary Resuscitation: The artificial substitution of heart and lung action as indicated for heart arrest resulting from electric shock, drowning, respiratory arrest, or other causes. The two major components of cardiopulmonary resuscitation are artificial ventilation and closed-chest cardiac massage. [NIH] Cardiorespiratory: Relating to the heart and lungs and their function. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Cardiovascular Physiology: Functions and activities of the cardiovascular system as a whole or of any of its parts. [NIH] Cardiovascular System: The heart and the blood vessels by which blood is pumped and circulated through the body. [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] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] Case-Control Studies: Studies which start with the identification of persons with a disease of interest and a control (comparison, referent) group without the disease. The relationship of an attribute to the disease is examined by comparing diseased and non-diseased persons with regard to the frequency or levels of the attribute in each group. [NIH]

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Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Catheter: A flexible tube used to deliver fluids into or withdraw fluids from the body. [NIH] Catheterization: Use or insertion of a tubular device into a duct, blood vessel, hollow organ, or body cavity for injecting or withdrawing fluids for diagnostic or therapeutic purposes. It differs from intubation in that the tube here is used to restore or maintain patency in obstructions. [NIH] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Adhesion: Adherence of cells to surfaces or to other cells. [NIH] Cell Adhesion Molecules: Surface ligands, usually glycoproteins, that mediate cell-to-cell adhesion. Their functions include the assembly and interconnection of various vertebrate systems, as well as maintenance of tissue integration, wound healing, morphogenic movements, cellular migrations, and metastasis. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Division: The fission of a cell. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [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 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] Cerebral Infarction: The formation of an area of necrosis in the cerebrum caused by an insufficiency of arterial or venous blood flow. Infarcts of the cerebrum are generally classified by hemisphere (i.e., left vs. right), lobe (e.g., frontal lobe infarction), arterial distribution (e.g., infarction, anterior cerebral artery), and etiology (e.g., embolic infarction). [NIH]

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] Cesarean Section: Extraction of the fetus by means of abdominal hysterotomy. [NIH] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH]

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Chemokines: Class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes. They can be divided into at least three structural branches: C (chemokines, C), CC (chemokines, CC), and CXC (chemokines, CXC), according to variations in a shared cysteine motif. [NIH] Chemopreventive: Natural or synthetic compound used to intervene in the early precancerous stages of carcinogenesis. [NIH] Chest Pain: Pressure, burning, or numbness in the chest. [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] 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] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Chronic Obstructive Pulmonary Disease: Collective term for chronic bronchitis and emphysema. [NIH] Circadian: Repeated more or less daily, i. e. on a 23- to 25-hour cycle. [NIH] Circadian Rhythm: The regular recurrence, in cycles of about 24 hours, of biological processes or activities, such as sensitivity to drugs and stimuli, hormone secretion, sleeping, feeding, etc. This rhythm seems to be set by a 'biological clock' which seems to be set by recurring daylight and darkness. [NIH] Circulatory system: The system that contains the heart and the blood vessels and moves blood throughout the body. This system helps tissues get enough oxygen and nutrients, and it helps them get rid of waste products. The lymph system, which connects with the blood system, is often considered part of the circulatory system. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Cleave: A double-stranded cut in DNA with a restriction endonuclease. [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] Clitoral: Pertaining to the clitoris. [EU] Clone: The term "clone" has acquired a new meaning. It is applied specifically to the bits of inserted foreign DNA in the hybrid molecules of the population. Each inserted segment originally resided in the DNA of a complex genome amid millions of other DNA segment.

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[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] Clozapine: A tricylic dibenzodiazepine, classified as an atypical antipsychotic agent. It binds several types of central nervous system receptors, and displays a unique pharmacological profile. Clozapine is a serotonin antagonist, with strong binding to 5-HT 2A/2C receptor subtype. It also displays strong affinity to several dopaminergic receptors, but shows only weak antagonism at the dopamine D2 receptor, a receptor commonly thought to modulate neuroleptic activity. Agranulocytosis is a major adverse effect associated with administration of this agent. [NIH] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Colloidal: Of the nature of a colloid. [EU] 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] Comorbidity: The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin

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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] 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 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] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Conduction: The transfer of sound waves, heat, nervous impulses, or electricity. [EU] Cone: One of the special retinal receptor elements which are presumed to be primarily concerned with perception of light and color stimuli when the eye is adapted to light. [NIH] Confidence Intervals: A range of values for a variable of interest, e.g., a rate, constructed so that this range has a specified probability of including the true value of the variable. [NIH] Congestive heart failure: Weakness of the heart muscle that leads to a buildup of fluid in body tissues. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjugation: 1. The act of joining together or the state of being conjugated. 2. A sexual process seen in bacteria, ciliate protozoa, and certain fungi in which nuclear material is exchanged during the temporary fusion of two cells (conjugants). In bacterial genetics a form of sexual reproduction in which a donor bacterium (male) contributes some, or all, of its DNA (in the form of a replicated set) to a recipient (female) which then incorporates differing genetic information into its own chromosome by recombination and passes the recombined set on to its progeny by replication. In ciliate protozoa, two conjugants of separate mating types exchange micronuclear material and then separate, each now being a fertilized cell. In certain fungi, the process involves fusion of two gametes, resulting in union of their nuclei and formation of a zygote. 3. In chemistry, the joining together of two compounds to produce another compound, such as the combination of a toxic product with

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some substance in the body to form a detoxified product, which is then eliminated. [EU] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue Diseases: A heterogeneous group of disorders, some hereditary, others acquired, characterized by abnormal structure or function of one or more of the elements of connective tissue, i.e., collagen, elastin, or the mucopolysaccharides. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constriction: The act of constricting. [NIH] Constriction, Pathologic: The condition of an anatomical structure's being constricted beyond normal dimensions. [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]

Contrast medium: A substance that is introduced into or around a structure and, because of the difference in absorption of x-rays by the contrast medium and the surrounding tissues, allows radiographic visualization of the structure. [EU] Conus: A large, circular, white patch around the optic disk due to the exposing of the sclera as a result of degenerative change or congenital abnormality in the choroid and retina. [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] 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 Artery Bypass: Surgical therapy of ischemic coronary artery disease achieved by grafting a section of saphenous vein, internal mammary artery, or other substitute between the aorta and the obstructed coronary artery distal to the obstructive lesion. [NIH] Coronary Circulation: The circulation of blood through the coronary vessels of the heart. [NIH]

Coronary Disease: Disorder of cardiac function due to an imbalance between myocardial function and the capacity of the coronary vessels to supply sufficient flow for normal function. It is a form of myocardial ischemia (insufficient blood supply to the heart muscle) caused by a decreased capacity of the coronary vessels. [NIH] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Coronary Vessels: The veins and arteries of the heart. [NIH] Corpus: The body of the uterus. [NIH] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to

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stress. [NIH] Criterion: A standard by which something may be judged. [EU] 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] Cyst: A sac or capsule filled with fluid. [NIH] Cystathionine beta-Synthase: A multifunctional pyridoxal phosphate enzyme. In the second stage of cysteine biosynthesis it catalyzes the reaction of homocysteine with serine to form cystathionine with the elimination of water. Deficiency of this enzyme leads to hyperhomocysteinemia and homocystinuria. EC 4.2.1.22. [NIH] Cytokines: Non-antibody proteins secreted by inflammatory leukocytes and some nonleukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. [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] Cytoprotection: The process by which chemical compounds provide protection to cells against harmful agents. [NIH] Defense Mechanisms: Unconscious process used by an individual or a group of individuals in order to cope with impulses, feelings or ideas which are not acceptable at their conscious level; various types include reaction formation, projection and self reversal. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dermatitis: Any inflammation of the skin. [NIH] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Dialyzer: A part of the hemodialysis machine. (See hemodialysis under dialysis.) The dialyzer has two sections separated by a membrane. One section holds dialysate. The other holds the patient's blood. [NIH] Diaphragm: The musculofibrous partition that separates the thoracic cavity from the abdominal cavity. Contraction of the diaphragm increases the volume of the thoracic cavity aiding inspiration. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Dihydroergotamine: A derivative of ergotamine prepared by the catalytic hydrogenation of ergotamine. It is used as a vasoconstrictor, specifically for the therapy of migraine. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Dilatation: The act of dilating. [NIH]

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Dilatation, Pathologic: The condition of an anatomical structure's being dilated beyond normal dimensions. [NIH] Dilation: A process by which the pupil is temporarily enlarged with special eye drops (mydriatic); allows the eye care specialist to better view the inside of the eye. [NIH] Dilution: A diluted or attenuated medicine; in homeopathy, the diffusion of a given quantity of a medicinal agent in ten or one hundred times the same quantity of water. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis. [NIH] Dislocation: The displacement of any part, more especially of a bone. Called also luxation. [EU]

Dissection: Cutting up of an organism for study. [NIH] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] Dosimetry: All the methods either of measuring directly, or of measuring indirectly and computing, absorbed dose, absorbed dose rate, exposure, exposure rate, dose equivalent, and the science associated with these methods. [NIH] Double Outlet Right Ventricle: Incomplete transposition of the great vessels in which both the aorta and the pulmonary artery arise from the right ventricle, often associated with a subaortic ventricular septal defect. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated

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dose and no-observed-adverse-effect level. [NIH] Duodenum: The first part of the small intestine. [NIH] Dysmenorrhea: Painful menstruation. [NIH] Echocardiography: Ultrasonic recording of the size, motion, and composition of the heart and surrounding tissues. The standard approach is transthoracic. [NIH] Eclampsia: Onset of convulsions or coma in a previously diagnosed pre-eclamptic patient. [NIH]

Ectopia Lentis: Congenital displacement of the lens resulting from defective zonule formation. [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] Elastic: Susceptible of resisting and recovering from stretching, compression or distortion applied by a force. [EU] Elastin: The protein that gives flexibility to tissues. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electric shock: A dangerous patho-physiological effect resulting from an electric current passing through the body of a human or animal. [NIH] Electrocoagulation: Electrosurgical procedures used to treat hemorrhage (e.g., bleeding ulcers) and to ablate tumors, mucosal lesions, and refractory arrhythmias. [NIH] Electrode: Component of the pacing system which is at the distal end of the lead. It is the interface with living cardiac tissue across which the stimulus is transmitted. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH]

Elementary Particles: Individual components of atoms, usually subatomic; subnuclear particles are usually detected only when the atomic nucleus decays and then only transiently, as most of them are unstable, often yielding pure energy without substance, i.e., radiation. [NIH] 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] Emboli: 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] 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] Embolization: The blocking of an artery by a clot or foreign material. Embolization can be

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done as treatment to block the flow of blood to a tumor. [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] Emphysema: A pathological accumulation of air in tissues or organs. [NIH] Emulsion: A preparation of one liquid distributed in small globules throughout the body of a second liquid. The dispersed liquid is the discontinuous phase, and the dispersion medium is the continuous phase. When oil is the dispersed liquid and an aqueous solution is the continuous phase, it is known as an oil-in-water emulsion, whereas when water or aqueous solution is the dispersed phase and oil or oleaginous substance is the continuous phase, it is known as a water-in-oil emulsion. Pharmaceutical emulsions for which official standards have been promulgated include cod liver oil emulsion, cod liver oil emulsion with malt, liquid petrolatum emulsion, and phenolphthalein in liquid petrolatum emulsion. [EU] Encephalocele: Cerebral tissue herniation through a congenital or acquired defect in the skull. The majority of congenital encephaloceles occur in the occipital or frontal regions. Clinical features include a protuberant mass that may be pulsatile. The quantity and location of protruding neural tissue determines the type and degree of neurologic deficit. Visual defects, psychomotor developmental delay, and persistent motor deficits frequently occur. [NIH]

Endarterectomy: Surgical excision, performed under general anesthesia, of the atheromatous tunica intima of an artery. When reconstruction of an artery is performed as an endovascular procedure through a catheter, it is called atherectomy. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endonucleases: Enzymes that catalyze the hydrolysis of the internal bonds and thereby the formation of polynucleotides or oligonucleotides from ribo- or deoxyribonucleotide chains. EC 3.1.-. [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] Endothelins: 21-Amino-acid peptides produced by vascular endothelial cells and functioning as potent vasoconstrictors. The endothelin family consists of three members, endothelin-1, endothelin-2, and endothelin-3. All three peptides contain 21 amino acids, but vary in amino acid composition. The three peptides produce vasoconstrictor and pressor responses in various parts of the body. However, the quantitative profiles of the pharmacological activities are considerably different among the three isopeptides. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium, Lymphatic: Unbroken cellular lining (intima) of the lymph vessels (e.g., the high endothelial lymphatic venules). It is more permeable than vascular endothelium, lacking selective absorption and functioning mainly to remove plasma proteins that have filtered through the capillaries into the tissue spaces. [NIH] Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the

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entire vascular system and regulate the transport of macromolecules and blood components from interstitium to lumen; this function has been most intensively studied in the blood capillaries. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxin: Toxin from cell walls of bacteria. [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] Eosinophils: Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. [NIH] Epidemiological: Relating to, or involving epidemiology. [EU] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] 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] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Epitope: A molecule or portion of a molecule capable of binding to the combining site of an antibody. For every given antigenic determinant, the body can construct a variety of antibody-combining sites, some of which fit almost perfectly, and others which barely fit. [NIH]

Erectile: The inability to get or maintain an erection for satisfactory sexual intercourse. Also called impotence. [NIH] Erection: The condition of being made rigid and elevated; as erectile tissue when filled with blood. [EU] Ergotamine: A vasoconstrictor found in ergot of Central Europe. It is an alpha-1 selective adrenergic agonist and is commonly used in the treatment of migraine headaches. [NIH] Erythrocyte Volume: Volume of circulating erythrocytes. It is usually measured by radioisotope dilution technique. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Esophageal: Having to do with the esophagus, the muscular tube through which food passes from the throat to the stomach. [NIH] Esophageal Varices: Stretched veins in the esophagus that occur when the liver is not working properly. If the veins burst, the bleeding can cause death. [NIH]

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Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Estrogen: One of the two female sex hormones. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [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] Exercise Test: Controlled physical activity, more strenuous than at rest, which is performed in order to allow assessment of physiological functions, particularly cardiovascular and pulmonary, but also aerobic capacity. Maximal (most intense) exercise is usually required but submaximal exercise is also used. The intensity of exercise is often graded, using criteria such as rate of work done, oxygen consumption, and heart rate. Physiological data obtained from an exercise test may be used for diagnosis, prognosis, and evaluation of disease severity, and to evaluate therapy. Data may also be used in prescribing exercise by determining a person's exercise capacity. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] 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 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] Extraction: The process or act of pulling or drawing out. [EU] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [EU] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]

Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Femoral: Pertaining to the femur, or to the thigh. [EU] Femoral Artery: The main artery of the thigh, a continuation of the external iliac artery. [NIH] Femoral Neck Fractures: Fractures of the short, constricted portion of the thigh bone between the femur head and the trochanters. It excludes intertrochanteric fractures which

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are hip fractures. [NIH] Femoral Vein: The vein accompanying the femoral artery in the same sheath; it is a continuation of the popliteal vein and becomes the external iliac vein. [NIH] Femur: The longest and largest bone of the skeleton, it is situated between the hip and the knee. [NIH] Fetal Development: Morphologic and physiologic growth and development of the mammalian embryo or fetus. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] Fibrinolysis: The natural enzymatic dissolution of fibrin. [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] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fibula: The bone of the lower leg lateral to and smaller than the tibia. In proportion to its length, it is the most slender of the long bones. [NIH] Filtration: The passage of a liquid through a filter, accomplished by gravity, pressure, or vacuum (suction). [EU] Fistula: Abnormal communication most commonly seen between two internal organs, or between an internal organ and the surface of the body. [NIH] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral, anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] Flank Pain: Pain emanating from below the ribs and above the ilium. [NIH]

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Flatus: Gas passed through the rectum. [NIH] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fluorocarbons: Liquid perfluorinated carbon compounds which may or may not contain a hetero atom such as nitrogen, oxygen or sulfur, but do not contain another halogen or hydrogen atom. This concept includes fluorocarbon emulsions and fluorocarbon blood substitutes. [NIH] Folate: A B-complex vitamin that is being studied as a cancer prevention agent. Also called folic acid. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Folic Acid: N-(4-(((2-Amino-1,4-dihydro-4-oxo-6-pteridinyl)methyl)amino)benzoyl)-Lglutamic acid. A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses. Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia. [NIH] Foramen: A natural hole of perforation, especially one in a bone. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Fossa: A cavity, depression, or pit. [NIH] Fovea: The central part of the macula that provides the sharpest vision. [NIH] Friction: Surface resistance to the relative motion of one body against the rubbing, sliding, rolling, or flowing of another with which it is in contact. [NIH] Frontal Lobe: The anterior part of the cerebral hemisphere. [NIH] Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gangrene: Death and putrefaction of tissue usually due to a loss of blood supply. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gas exchange: Primary function of the lungs; transfer of oxygen from inhaled air into the blood and of carbon dioxide from the blood into the lungs. [NIH] Gastric: Having to do with the stomach. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] 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]

Generator: Any system incorporating a fixed parent radionuclide from which is produced a daughter radionuclide which is to be removed by elution or by any other method and used

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in a radiopharmaceutical. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic Markers: A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genital: Pertaining to the genitalia. [EU] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Germfree: Free from all living micro-organisms. [NIH] Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [NIH] Glucuronic Acid: Derivatives of uronic acid found throughout the plant and animal kingdoms. They detoxify drugs and toxins by conjugating with them to form glucuronides in the liver which are more water-soluble metabolites that can be easily eliminated from the body. [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] Glycosylation: The chemical or biochemical addition of carbohydrate or glycosyl groups to other chemicals, especially peptides or proteins. Glycosyl transferases are used in this biochemical reaction. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Gp120: 120-kD HIV envelope glycoprotein which is involved in the binding of the virus to its membrane receptor, the CD4 molecule, found on the surface of certain cells in the body. [NIH]

Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Graft Rejection: An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. [NIH] Grafting: The operation of transfer of tissue from one site to another. [NIH] Grasses: A large family, Gramineae, of narrow-leaved herbaceous monocots. Many grasses produce highly allergenic pollens and are hosts to cattle parasites and toxic fungi. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH]

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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] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Heart Arrest: Sudden and usually momentary cessation of the heart beat. This sudden cessation may, but not usually, lead to death, sudden, cardiac. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Heartbeat: One complete contraction of the heart. [NIH] Hematology: A subspecialty of internal medicine concerned with morphology, physiology, and pathology of the blood and blood-forming tissues. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH] Hemodynamics: The movements of the blood and the forces involved in systemic or regional blood circulation. [NIH] 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] Hemolytic: A disease that affects the blood and blood vessels. It destroys red blood cells, cells that cause the blood to clot, and the lining of blood vessels. HUS is often caused by the Escherichia coli bacterium in contaminated food. People with HUS may develop acute renal failure. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemorrhoids: Varicosities of the hemorrhoidal venous plexuses. [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]

Heparin: Heparinic acid. A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. [NIH] Hepatic: Refers to the liver. [NIH]

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Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]

Hip Fractures: Fractures of the femur head, the femur neck, the trochanters, or the inter- or subtrochanteric region. Excludes fractures of the acetabulum and fractures of the femoral shaft below the subtrochanteric region. For the fractures of the femur neck the specific term femoral neck fractures is available. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homotypic: Adhesion between neutrophils. [NIH] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Hormone Replacement Therapy: Therapeutic use of hormones to alleviate the effects of hormone deficiency. [NIH] Hospital Mortality: A vital statistic measuring or recording the rate of death from any cause in hospitalized populations. [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridoma: A hybrid cell resulting from the fusion of a specific antibody-producing spleen cell with a myeloma cell. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydrogenation: Specific method of reduction in which hydrogen is added to a substance by the direct use of gaseous hydrogen. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hyperhomocysteinemia: An inborn error of methionone metabolism which produces an excess of homocysteine in the blood. It is often caused by a deficiency of cystathionine betasynthase and is a risk factor for coronary vascular disease. [NIH] Hyperoxia: An abnormal increase in the amount of oxygen in the tissues and organs. [NIH]

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Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hyperventilation: A pulmonary ventilation rate faster than is metabolically necessary for the exchange of gases. It is the result of an increased frequency of breathing, an increased tidal volume, or a combination of both. It causes an excess intake of oxygen and the blowing off of carbon dioxide. [NIH] 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] Hypoxic: Having too little oxygen. [NIH] Hysterotomy: An incision in the uterus, performed through either the abdomen or the vagina. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Iliac Vein: A vein on either side of the body which is formed by the union of the external and internal iliac veins and passes upward to join with its fellow of the opposite side to form the inferior vena cava. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunoassay: Immunochemical assay or detection of a substance by serologic or immunologic methods. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance. [NIH] Immunoelectrophoresis: A technique that combines protein electrophoresis and double immunodiffusion. In this procedure proteins are first separated by gel electrophoresis (usually agarose), then made visible by immunodiffusion of specific antibodies. A distinct elliptical precipitin arc results for each protein detectable by the antisera. [NIH] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] Impotence: The inability to perform sexual intercourse. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH]

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Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

Inferior vena cava: A large vein that empties into the heart. It carries blood from the legs and feet, and from organs in the abdomen and pelvis. [NIH] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Inlay: In dentistry, a filling first made to correspond with the form of a dental cavity and then cemented into the cavity. [NIH] Innervation: 1. The distribution or supply of nerves to a part. 2. The supply of nervous energy or of nerve stimulus sent to a part. [EU] 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] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestines: The section of the alimentary canal from the stomach to the anus. It includes the large intestine and small intestine. [NIH] Intracellular: Inside a cell. [NIH] Intracranial Aneurysm: A saclike dilatation of the walls of a blood vessel, usually an artery. [NIH]

Intramuscular: IM. Within or into muscle. [NIH] Intravascular: Within a vessel or vessels. [EU]

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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]

Invertebrates: Animals that have no spinal column. [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] Irradiation: The use of high-energy radiation from x-rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Irradiation is also called radiation therapy, radiotherapy, and x-ray therapy. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] 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] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Kidney stone: A stone that develops from crystals that form in urine and build up on the inner surfaces of the kidney, in the renal pelvis, or in the ureters. [NIH] Kinetic: Pertaining to or producing motion. [EU] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Larynx: An irregularly shaped, musculocartilaginous tubular structure, lined with mucous membrane, located at the top of the trachea and below the root of the tongue and the hyoid bone. It is the essential sphincter guarding the entrance into the trachea and functioning secondarily as the organ of voice. [NIH] Latency: The period of apparent inactivity between the time when a stimulus is presented and the moment a response occurs. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no

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troublesome effect. [NIH] Lavage: A cleaning of the stomach and colon. Uses a special drink and enemas. [NIH] Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] Lepirudin: A drug that inhibits blood clotting; it is being studied in cancer treatment. [NIH] Lethal: Deadly, fatal. [EU] Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Leukotrienes: A family of biologically active compounds derived from arachidonic acid by oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal tract and the immune system. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]

Lidocaine: A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of procaine but its duration of action is shorter than that of bupivacaine or prilocaine. [NIH] Ligaments: Shiny, flexible bands of fibrous tissue connecting together articular extremities of bones. They are pliant, tough, and inextensile. [NIH] Ligands: A RNA simulation method developed by the MIT. [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lipid: Fat. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipopolysaccharide: Substance consisting of polysaccaride and lipid. [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] Liver Transplantation: The transference of a part of or an entire liver from one human or animal to another. [NIH] Lobe: A portion of an organ such as the liver, lung, breast, or brain. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Loop: A wire usually of platinum bent at one end into a small loop (usually 4 mm inside diameter) and used in transferring microorganisms. [NIH] Lubricants: Oily or slippery substances. [NIH] Lubrication: The application of a substance to diminish friction between two surfaces. It may refer to oils, greases, and similar substances for the lubrication of medical equipment

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but it can be used for the application of substances to tissue to reduce friction, such as lotions for skin and vaginal lubricants. [NIH] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] Lung Transplantation: The transference of either one or both of the lungs from one human or animal to another. [NIH] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] Luxation: The displacement of the particular surface of a bone from its normal joint, without fracture. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] 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] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lytic: 1. Pertaining to lysis or to a lysin. 2. Producing lysis. [EU] 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] Malignancy: A cancerous tumor that can invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]

Mammary: Pertaining to the mamma, or breast. [EU] Mammogram: An x-ray of the breast. [NIH] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Matrix metalloproteinase: A member of a group of enzymes that can break down proteins,

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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] Mechanical ventilation: Use of a machine called a ventilator or respirator to improve the exchange of air between the lungs and the atmosphere. [NIH] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Megaloblastic: A large abnormal red blood cell appearing in the blood in pernicious anaemia. [EU] Melanin: The substance that gives the skin its color. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Menopause: Permanent cessation of menstruation. [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mental Retardation: Refers to sub-average general intellectual functioning which originated during the developmental period and is associated with impairment in adaptive behavior. [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] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH]

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Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microcalcifications: Tiny deposits of calcium in the breast that cannot be felt but can be detected on a mammogram. A cluster of these very small specks of calcium may indicate that cancer is present. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Micro-organism: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microspheres: Small uniformly-sized spherical particles frequently radioisotopes or various reagents acting as tags or markers. [NIH]

labeled

with

Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [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 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] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] 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]

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Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. [NIH] Mononuclear: A cell with one nucleus. [NIH] Monotherapy: A therapy which uses only one drug. [EU] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Muscle Contraction: A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments. [NIH] Muscle Relaxation: That phase of a muscle twitch during which a muscle returns to a resting position. [NIH] Musculoskeletal System: Themuscles, bones, and cartilage of the body. [NIH] Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [EU] Myeloma: Cancer that arises in plasma cells, a type of white blood cell. [NIH] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocardial Ischemia: A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (coronary arteriosclerosis), to obstruction by a thrombus (coronary thrombosis), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result in necrosis of cardiac muscle (myocardial infarction). [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myofibrils: Highly organized bundles of actin, myosin, and other proteins in the cytoplasm of skeletal and cardiac muscle cells that contract by a sliding filament mechanism. [NIH] Myosin: Chief protein in muscle and the main constituent of the thick filaments of muscle fibers. In conjunction with actin, it is responsible for the contraction and relaxation of muscles. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Nephritis: Inflammation of the kidney; a focal or diffuse proliferative or destructive process which may involve the glomerulus, tubule, or interstitial renal tissue. [EU] Nephropathy: Disease of the kidneys. [EU]

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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 Regeneration: Renewal or physiological repair of damaged nerve tissue. [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] Neural tube defects: These defects include problems stemming from fetal development of the spinal cord, spine, brain, and skull, and include birth defects such as spina bifida, anencephaly, and encephalocele. Neural tube defects occur early in pregnancy at about 4 to 6 weeks, usually before a woman knows she is pregnant. Many babies with neural tube defects have difficulty walking and with bladder and bowel control. [NIH] Neuroleptic: A term coined to refer to the effects on cognition and behaviour of antipsychotic drugs, which produce a state of apathy, lack of initiative, and limited range of emotion and in psychotic patients cause a reduction in confusion and agitation and normalization of psychomotor activity. [EU] Neurologic: Having to do with nerves or the nervous system. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Blockade: The intentional interruption of transmission at the neuromuscular junction by external agents, usually neuromuscular blocking agents. It is distinguished from nerve block in which nerve conduction is interrupted rather than neuromuscular transmission. Neuromuscular blockade is commonly used to produce muscle relaxation as an adjunct to anesthesia during surgery and other medical procedures. It is also often used as an experimental manipulation in basic research. It is not strictly speaking anesthesia but is grouped here with anesthetic techniques. The failure of neuromuscular transmission as a result of pathological processes is not included here. [NIH] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neuropeptides: Peptides released by neurons as intercellular messengers. Many neuropeptides are also hormones released by non-neuronal cells. [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] Neutralization: An act or process of neutralizing. [EU] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutrophil: A type of white blood cell. [NIH] 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

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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] Noble Gases: Gases which are members of the zero group of the periodic system. These gases generally do not react chemically. [NIH] Nonmalignant: Not cancerous. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Normotensive: 1. Characterized by normal tone, tension, or pressure, as by normal blood pressure. 2. A person with normal blood pressure. [EU] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclear Medicine: A specialty field of radiology concerned with diagnostic, therapeutic, and investigative use of radioactive compounds in a pharmaceutical form. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Observational study: An epidemiologic study that does not involve any intervention, experimental or otherwise. Such a study may be one in which nature is allowed to take its course, with changes in one characteristic being studied in relation to changes in other characteristics. Analytical epidemiologic methods, such as case-control and cohort study designs, are properly called observational epidemiology because the investigator is observing without intervention other than to record, classify, count, and statistically analyze results. [NIH] Odds Ratio: The ratio of two odds. The exposure-odds ratio for case control data is the ratio of the odds in favor of exposure among cases to the odds in favor of exposure among noncases. The disease-odds ratio for a cohort or cross section is the ratio of the odds in favor of disease among the exposed to the odds in favor of disease among the unexposed. The prevalence-odds ratio refers to an odds ratio derived cross-sectionally from studies of prevalent cases. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Ophthalmology: A surgical specialty concerned with the structure and function of the eye and the medical and surgical treatment of its defects and diseases. [NIH] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum;

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lysomomes; plastids; and vacuoles. [NIH] Orgasm: The crisis of sexual excitement in either humans or animals. [NIH] Orthopaedic: Pertaining to the correction of deformities of the musculoskeletal system; pertaining to orthopaedics. [EU] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [NIH] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Oxides: Binary compounds of oxygen containing the anion O(2-). The anion combines with metals to form alkaline oxides and non-metals to form acidic oxides. [NIH] Oximetry: The determination of oxygen-hemoglobin saturation of blood either by withdrawing a sample and passing it through a classical photoelectric oximeter or by electrodes attached to some translucent part of the body like finger, earlobe, or skin fold. It includes non-invasive oxygen monitoring by pulse oximetry. [NIH] Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Oxygenase: Enzyme which breaks down heme, the iron-containing oxygen-carrying constituent of the red blood cells. [NIH] Oxygenator: An apparatus by which oxygen is introduced into the blood during circulation outside the body, as during open heart surgery. [NIH] Pacemaker: An object or substance that influences the rate at which a certain phenomenon occurs; often used alone to indicate the natural cardiac pacemaker or an artificial cardiac pacemaker. In biochemistry, a substance whose rate of reaction sets the pace for a series of interrelated reactions. [EU] Paediatric: Of or relating to the care and medical treatment of children; belonging to or concerned with paediatrics. [EU] 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]

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Panic: A state of extreme acute, intense anxiety and unreasoning fear accompanied by disorganization of personality function. [NIH] Paradoxical: Occurring at variance with the normal rule. [EU] Parietal: 1. Of or pertaining to the walls of a cavity. 2. Pertaining to or located near the parietal bone, as the parietal lobe. [EU] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Pelvic: Pertaining to the pelvis. [EU] Pelvis: The lower part of the abdomen, located between the hip bones. [NIH] Penis: The external reproductive organ of males. It is composed of a mass of erectile tissue enclosed in three cylindrical fibrous compartments. Two of the three compartments, the corpus cavernosa, are placed side-by-side along the upper part of the organ. The third compartment below, the corpus spongiosum, houses the urethra. [NIH] Peptic: Pertaining to pepsin or to digestion; related to the action of gastric juices. [EU] Peptic Ulcer: An ulceration of the mucous membrane of the esophagus, stomach or duodenum, caused by the action of the acid gastric juice. [NIH] Peptic Ulcer Hemorrhage: Bleeding from a peptic ulcer. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Peptide T: N-(N-(N(2)-(N-(N-(N-(N-D-Alanyl L-seryl)-L-threonyl)-L-threonyl) L-threonyl)L-asparaginyl)-L-tyrosyl) L-threonine. Octapeptide sharing sequence homology with HIV envelope protein gp120. It is potentially useful as antiviral agent in AIDS therapy. The core pentapeptide sequence, TTNYT, consisting of amino acids 4-8 in peptide T, is the HIV envelope sequence required for attachment to the CD4 receptor. [NIH] Perception: The ability quickly and accurately to recognize similarities and differences among presented objects, whether these be pairs of words, pairs of number series, or multiple sets of these or other symbols such as geometric figures. [NIH] Percutaneous: Performed through the skin, as injection of radiopacque material in radiological examination, or the removal of tissue for biopsy accomplished by a needle. [EU] Perforation: 1. The act of boring or piercing through a part. 2. A hole made through a part or substance. [EU] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Perioperative: Around the time of surgery; usually lasts from the time of going into the hospital or doctor's office for surgery until the time the patient goes home. [NIH] Peripheral Vascular Disease: Disease in the large blood vessels of the arms, legs, and feet. People who have had diabetes for a long time may get this because major blood vessels in

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their arms, legs, and feet are blocked and these limbs do not receive enough blood. The signs of PVD are aching pains in the arms, legs, and feet (especially when walking) and foot sores that heal slowly. Although people with diabetes cannot always avoid PVD, doctors say they have a better chance of avoiding it if they take good care of their feet, do not smoke, and keep both their blood pressure and diabetes under good control. [NIH] Pernicious: Tending to a fatal issue. [EU] Pernicious anemia: A type of anemia (low red blood cell count) caused by the body's inability to absorb vitamin B12. [NIH] Peroneal Nerve: The lateral of the two terminal branches of the sciatic nerve. The peroneal (or fibular) nerve provides motor and sensory innervation to parts of the leg and foot. [NIH] PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [EU] Phallic: Pertaining to the phallus, or penis. [EU] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharmacotherapy: A regimen of using appetite suppressant medications to manage obesity by decreasing appetite or increasing the feeling of satiety. These medications decrease appetite by increasing serotonin or catecholamine—two brain chemicals that affect mood and appetite. [NIH] 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] Phlebitis: Inflammation of a vein. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylase: An enzyme of the transferase class that catalyzes the phosphorylysis of a terminal alpha-1,4-glycosidic bond at the non-reducing end of a glycogen molecule, releasing a glucose 1-phosphate residue. Phosphorylase should be qualified by the natural substance acted upon. EC 2.4.1.1. [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Photocoagulation: Using a special strong beam of light (laser) to seal off bleeding blood vessels such as in the eye. The laser can also burn away blood vessels that should not have grown in the eye. This is the main treatment for diabetic retinopathy. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase

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"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] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma 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] 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]

Pleura: The thin serous membrane enveloping the lungs and lining the thoracic cavity. [NIH] Pleural: A circumscribed area of hyaline whorled fibrous tissue which appears on the

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surface of the parietal pleura, on the fibrous part of the diaphragm or on the pleura in the interlobar fissures. [NIH] Pleural cavity: A space enclosed by the pleura (thin tissue covering the lungs and lining the interior wall of the chest cavity). It is bound by thin membranes. [NIH] Pleural Effusion: Presence of fluid in the pleural cavity resulting from excessive transudation or exudation from the pleural surfaces. It is a sign of disease and not a diagnosis in itself. [NIH] Pneumonia: Inflammation of the lungs. [NIH] Polymers: Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., polypeptides, proteins, plastics). [NIH] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Popliteal: Compression of the nerve at the neck of the fibula. [NIH] Popliteal Vein: The vein formed by the union of the anterior and posterior tibial veins; it courses through the popliteal space and becomes the femoral vein. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postoperative: After surgery. [NIH] Postphlebitic Syndrome: Post-thrombotic complications, including destruction of the valves of the deep veins and communication veins of the leg, and obliteration of the thrombosed veins rather than recanalization, resulting in chronic venous insufficiency, marked by edema, stasis dermatitis, and ulceration of the leg. [NIH] Post-traumatic: Occurring as a result of or after injury. [EU] 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] Precancerous: A term used to describe a condition that may (or is likely to) become cancer. Also called premalignant. [NIH] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Preeclampsia: A toxaemia of late pregnancy characterized by hypertension, edema, and proteinuria, when convulsions and coma are associated, it is called eclampsia. [EU] Pre-eclamptic: A syndrome characterized by hypertension, albuminuria, and generalized oedema, occurring only in pregnancy. [NIH] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH]

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Priapism: Persistent abnormal erection of the penis, usually without sexual desire, and accompanied by pain and tenderness. It is seen in diseases and injuries of the spinal cord, and may be caused by vesical calculus and certain injuries to the penis. [EU] Primary Prevention: Prevention of disease or mental disorders in susceptible individuals or populations through promotion of health, including mental health, and specific protection, as in immunization, as distinguished from the prevention of complications or after-effects of existing disease. [NIH] Primary tumor: The original tumor. [NIH] Procaine: A local anesthetic of the ester type that has a slow onset and a short duration of action. It is mainly used for infiltration anesthesia, peripheral nerve block, and spinal block. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1016). [NIH] Proenzymes: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH] Progeny: The offspring produced in any generation. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promyelocytic leukemia: A type of acute myeloid leukemia, a quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. [NIH]

Prone: Having the front portion of the body downwards. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Proportional: Being in proportion : corresponding in size, degree, or intensity, having the same or a constant ratio; of, relating to, or used in determining proportions. [EU] Prospective Studies: Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] 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 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

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and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. Quaternary protein structure describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). [NIH] Protein 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] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not working properly. [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] Prothrombin: A plasma protein that is the inactive precursor of thrombin. It is converted to thrombin by a prothrombin activator complex consisting of factor Xa, factor V, phospholipid, and calcium ions. Deficiency of prothrombin leads to hypoprothrombinemia. [NIH]

Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [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 Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right

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ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary Circulation: The circulation of blood through the lungs. [NIH] Pulmonary Edema: An accumulation of an excessive amount of watery fluid in the lungs, may be caused by acute exposure to dangerous concentrations of irritant gasses. [NIH] Pulmonary Embolism: Embolism in the pulmonary artery or one of its branches. [NIH] Pulmonary hypertension: Abnormally high blood pressure in the arteries of the lungs. [NIH] Pulmonary Ventilation: The total volume of gas per minute inspired or expired measured in liters per minute. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]

Pupil: The aperture in the iris through which light passes. [NIH] Purpura: Purplish or brownish red discoloration, easily visible through the epidermis, caused by hemorrhage into the tissues. [NIH] Putrefaction: The process of decomposition of animal and vegetable matter by living organisms. [NIH] Quantitative Structure-Activity Relationship: A quantitative prediction of the biological, ecotoxicological or pharmaceutical activity of a molecule. It is based upon structure and activity information gathered from a series of similar compounds. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radioactive: Giving off radiation. [NIH] Radiography: Examination of any part of the body for diagnostic purposes by means of roentgen rays, recording the image on a sensitized surface (such as photographic film). [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [NIH] Radiology: A specialty concerned with the use of x-ray and other forms of radiant energy in the diagnosis and treatment of disease. [NIH] Radiopharmaceutical: Any medicinal product which, when ready for use, contains one or more radionuclides (radioactive isotopes) included for a medicinal purpose. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a

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cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] 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] 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] 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] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Refractory: Not readily yielding to treatment. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Relative risk: The ratio of the incidence rate of a disease among individuals exposed to a specific risk factor to the incidence rate among unexposed individuals; synonymous with risk ratio. Alternatively, the ratio of the cumulative incidence rate in the exposed to the cumulative incidence rate in the unexposed (cumulative incidence ratio). The term relative risk has also been used synonymously with odds ratio. This is because the odds ratio and relative risk approach each other if the disease is rare ( 5 percent of population) and the number of subjects is large. [NIH] Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renal Dialysis: Removal of certain elements from the blood based on the difference in their rates of diffusion through a semipermeable membrane. [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] 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] Resection: Removal of tissue or part or all of an organ by surgery. [NIH]

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Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Respirator: A mechanical device that helps a patient breathe; a mechanical ventilator. [NIH] Respiratory distress syndrome: A lung disease that occurs primarily in premature infants; the newborn must struggle for each breath and blueing of its skin reflects the baby's inability to get enough oxygen. [NIH] Respiratory Physiology: Functions and activities of the respiratory tract as a whole or of any of its parts. [NIH] Respiratory System: The tubular and cavernous organs and structures, by means of which pulmonary ventilation and gas exchange between ambient air and the blood are brought about. [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Resuscitation: The restoration to life or consciousness of one apparently dead; it includes such measures as artificial respiration and cardiac massage. [EU] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retrospective: Looking back at events that have already taken place. [NIH] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Rod: A reception for vision, located in the retina. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Saphenous: Applied to certain structures in the leg, e. g. nerve vein. [NIH] Saphenous Vein: The vein which drains the foot and leg. [NIH] Sarcomere: The repeating structural unit of a striated muscle fiber. [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

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create pictures of areas inside the body. [NIH] Sciatic Nerve: A nerve which originates in the lumbar and sacral spinal cord (L4 to S3) and supplies motor and sensory innervation to the lower extremity. The sciatic nerve, which is the main continuation of the sacral plexus, is the largest nerve in the body. It has two major branches, the tibial nerve and the peroneal nerve. [NIH] Sclerotherapy: Treatment of varicose veins, hemorrhoids, gastric and esophageal varices, and peptic ulcer hemorrhage by injection or infusion of chemical agents which cause localized thrombosis and eventual fibrosis and obliteration of the vessels. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Secondary tumor: Cancer that has spread from the organ in which it first appeared to another organ. For example, breast cancer cells may spread (metastasize) to the lungs and cause the growth of a new tumor. When this happens, the disease is called metastatic breast cancer, and the tumor in the lungs is called a secondary tumor. Also called secondary cancer. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Selective estrogen receptor modulator: SERM. A drug that acts like estrogen on some tissues, but blocks the effect of estrogen on other tissues. Tamoxifen and raloxifene are SERMs. [NIH] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [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] Sepsis: The presence of bacteria in the bloodstream. [NIH] Septal: An abscess occurring at the root of the tooth on the proximal surface. [NIH] Septic: Produced by or due to decomposition by microorganisms; putrefactive. [EU] Sequela: Any lesion or affection following or caused by an attack of disease. [EU] Sequence Homology: The degree of similarity between sequences. Studies of amino acid and nucleotide sequences provide useful information about the genetic relatedness of certain species. [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] Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serous: Having to do with serum, the clear liquid part of blood. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral

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upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]

Shock, Cardiogenic: Shock resulting from diminution of cardiac output in heart disease. [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] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

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] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] 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] 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] Spectroscopic: The recognition of elements through their emission spectra. [NIH] Sphincter: A ringlike band of muscle fibres that constricts a passage or closes a natural orifice; called also musculus sphincter. [EU] Spina bifida: A defect in development of the vertebral column in which there is a central deficiency of the vertebral lamina. [NIH]

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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] Stabilization: The creation of a stable state. [EU] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH]

Stasis: A word termination indicating the maintenance of (or maintaining) a constant level; preventing increase or multiplication. [EU] Statistically significant: Describes a mathematical measure of difference between groups. The difference is said to be statistically significant if it is greater than what might be expected to happen by chance alone. [NIH] Steady state: Dynamic equilibrium. [EU] Stent: A device placed in a body structure (such as a blood vessel or the gastrointestinal tract) to provide support and keep the structure open. [NIH] 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] Streptococci: A genus of spherical Gram-positive bacteria occurring in chains or pairs. They are widely distributed in nature, being important pathogens but often found as normal commensals in the mouth, skin, and intestine of humans and other animals. [NIH] Streptokinase: Streptococcal fibrinolysin . An enzyme produced by hemolytic streptococci. It hydrolyzes amide linkages and serves as an activator of plasminogen. It is used in thrombolytic therapy and is used also in mixtures with streptodornase (streptodornase and streptokinase). EC 3.4.-. [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] Subacute: Somewhat acute; between acute and chronic. [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] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substrate: A substance upon which an enzyme acts. [EU] Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts. [NIH]

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Subtrochanteric: Below a trochanter. [NIH] Suction: The removal of secretions, gas or fluid from hollow or tubular organs or cavities by means of a tube and a device that acts on negative pressure. [NIH] Sudden cardiac death: Cardiac arrest caused by an irregular heartbeat. [NIH] Sudden death: Cardiac arrest caused by an irregular heartbeat. The term "death" is somewhat misleading, because some patients survive. [NIH] Sulfates: Inorganic salts of sulfuric acid. [NIH] Sulfur: An element that is a member of the chalcogen family. It has an atomic symbol S, atomic number 16, and atomic weight 32.066. It is found in the amino acids cysteine and methionine. [NIH] Sulfuric acid: A strong acid that, when concentrated is extemely corrosive to the skin and mucous membranes. It is used in making fertilizers, dyes, electroplating, and industrial explosives. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Surface Plasmon Resonance: A biosensing technique in which biomolecules capable of binding to specific analytes or ligands are first immobilized on one side of a metallic film. Light is then focused on the opposite side of the film to excite the surface plasmons, that is, the oscillations of free electrons propagating along the film's surface. The refractive index of light reflecting off this surface is measured. When the immobilized biomolecules are bound by their ligands, an alteration in surface plasmons on the opposite side of the film is created which is directly proportional to the change in bound, or adsorbed, mass. Binding is measured by changes in the refractive index. The technique is used to study biomolecular interactions, such as antigen-antibody binding. [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] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire body. [NIH] Systemic disease: Disease that affects the whole body. [NIH] Systemic lupus erythematosus: SLE. A chronic inflammatory connective tissue disease marked by skin rashes, joint pain and swelling, inflammation of the kidneys, inflammation of the fibrous tissue surrounding the heart (i.e., the pericardium), as well as other problems. Not all affected individuals display all of these problems. May be referred to as lupus. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Systolic blood pressure: The maximum pressure in the artery produced as the heart contracts and blood begins to flow. [NIH] Tachycardia: Excessive rapidity in the action of the heart, usually with a heart rate above 100 beats per minute. [NIH] Tachypnea: Rapid breathing. [NIH] Tamoxifen: A first generation selective estrogen receptor modulator (SERM). It acts as an agonist for bone tissue and cholesterol metabolism but is an estrogen antagonist in mammary and uterine. [NIH] Technetium: The first artificially produced element and a radioactive fission product of

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uranium. The stablest isotope has a mass number 99 and is used diagnostically as a radioactive imaging agent. Technetium has the atomic symbol Tc, atomic number 43, and atomic weight 98.91. [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] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thigh: A leg; in anatomy, any elongated process or part of a structure more or less comparable to a leg. [NIH] Thoracic: Having to do with the chest. [NIH] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] 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] Thrombocytes: Blood cells that help prevent bleeding by causing blood clots to form. Also called platelets. [NIH] Thrombocytopenia: A decrease in the number of blood platelets. [NIH] Thromboembolism: Obstruction of a vessel by a blood clot that has been transported from a distant site by the blood stream. [NIH] Thrombolytic: 1. Dissolving or splitting up a thrombus. 2. A thrombolytic agent. [EU] Thrombolytic Therapy: Use of infusions of fibrinolytic agents to destroy or dissolve thrombi in blood vessels or bypass grafts. [NIH] Thrombopenia: Reduction in the number of platelets in the blood. [NIH] Thrombophlebitis: Inflammation of a vein associated with thrombus formation. [NIH] Thrombosed: A localized clot that either forms in the vein of a hemorrhoid or arises from a ruptured hemorrhoidal blood vessel. [NIH] Thromboses: The formation or presence of a blood clot within a blood vessel during life. [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] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Tibial Nerve: The medial terminal branch of the sciatic nerve. The tibial nerve fibers originate in lumbar and sacral spinal segments (L4 to S2). They supply motor and sensory innervation to parts of the calf and foot. [NIH] Tidal Volume: The volume of air inspired or expired during each normal, quiet respiratory cycle. Common abbreviations are TV or V with subscript T. [NIH] 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] Tonus: A state of slight tension usually present in muscles even when they are not undergoing active contraction. [NIH] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] Topical: On the surface of the body. [NIH] Torsion: A twisting or rotation of a bodily part or member on its axis. [NIH] Toxaemia: 1. The condition resulting from the spread of bacterial products (toxins) by the bloodstream. 2. A condition resulting from metabolic disturbances, e.g. toxaemia of pregnancy. [EU] 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] Trachea: The cartilaginous and membranous tube descending from the larynx and

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branching into the right and left main bronchi. [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transcutaneous: Transdermal. [EU] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transferases: Transferases are enzymes transferring a group, for example, the methyl group or a glycosyl group, from one compound (generally regarded as donor) to another compound (generally regarded as acceptor). The classification is based on the scheme "donor:acceptor group transferase". (Enzyme Nomenclature, 1992) EC 2. [NIH] 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] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Translocation: The movement of material in solution inside the body of the plant. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Tropomyosin: A protein found in the thin filaments of muscle fibers. It inhibits contraction of the muscle unless its position is modified by troponin. [NIH] Troponin: One of the minor protein components of skeletal muscle. Its function is to serve as the calcium-binding component in the troponin-tropomyosin B-actin-myosin complex by conferring calcium sensitivity to the cross-linked actin and myosin filaments. [NIH] Trypsin: A serine endopeptidase that is formed from trypsinogen in the pancreas. It is converted into its active form by enteropeptidase in the small intestine. It catalyzes hydrolysis of the carboxyl group of either arginine or lysine. EC 3.4.21.4. [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] Tumour: 1. Swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. A new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU] Tunica: A rather vague term to denote the lining coat of hollow organs, tubes, or cavities. [NIH]

Tunica Intima: The innermost coat of blood vessels, consisting of a thin lining of endothelial cells longitudinally oriented and continuous with the endothelium of capillaries on the one hand and the endocardium of the heart on the other. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is

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also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Ulceration: 1. The formation or development of an ulcer. 2. An ulcer. [EU] Ultrasonography: The visualization of deep structures of the body by recording the reflections of echoes of pulses of ultrasonic waves directed into the tissues. Use of ultrasound for imaging or diagnostic purposes employs frequencies ranging from 1.6 to 10 megahertz. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Uranium: A radioactive element of the actinide series of metals. It has an atomic symbol U, atomic number 92, and atomic weight 238.03. U-235 is used as the fissionable fuel in nuclear weapons and as fuel in nuclear power reactors. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Uric: A kidney stone that may result from a diet high in animal protein. When the body breaks down this protein, uric acid levels rise and can form stones. [NIH] Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] 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]

Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Urokinase: A drug that dissolves blood clots or prevents them from forming. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vaginal: Of or having to do with the vagina, the birth canal. [NIH] Valves: Flap-like structures that control the direction of blood flow through the heart. [NIH] Varicose: The common ulcer in the lower third of the leg or near the ankle. [NIH] Varicose vein: An abnormal swelling and tortuosity especially of the superficial veins of the legs. [EU] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasoactive: Exerting an effect upon the calibre of blood vessels. [EU] Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [NIH] Vasodilation: Physiological dilation of the blood vessels without anatomic change. For dilation with anatomic change, dilatation, pathologic or aneurysm (or specific aneurysm) is used. [NIH] Vasodilators: Any nerve or agent which induces dilatation of the blood vessels. [NIH]

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VE: The total volume of gas either inspired or expired in one minute. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Vena: A vessel conducting blood from the capillary bed to the heart. [NIH] Vena Cava Filters: Mechanical devices inserted in the inferior vena cava that prevent the migration of blood clots from deep venous thrombosis of the leg. [NIH] Venous: Of or pertaining to the veins. [EU] Venous blood: Blood that has given up its oxygen to the tissues and carries carbon dioxide back for gas exchange. [NIH] Venous Insufficiency: Inadequacy of the venous valves and impairment of venous return (venous stasis) usually from the legs, often with edema and sometimes with stasis ulcers at the ankle. [NIH] Venous Thrombosis: The formation or presence of a thrombus within a vein. [NIH] Ventilation: 1. In respiratory physiology, the process of exchange of air between the lungs and the ambient air. Pulmonary ventilation (usually measured in litres per minute) refers to the total exchange, whereas alveolar ventilation refers to the effective ventilation of the alveoli, in which gas exchange with the blood takes place. 2. In psychiatry, verbalization of one's emotional problems. [EU] Ventilator: A breathing machine that is used to treat respiratory failure by promoting ventilation; also called a respirator. [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] Ventricular: Pertaining to a ventricle. [EU] Ventricular Dysfunction: A condition in which the ventricles of the heart exhibit a decreased functionality. [NIH] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vertebrae: A bony unit of the segmented spinal column. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] 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] Warfarin: An anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent coagulation factors. Warfarin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization. It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Warfarin is also used as a rodenticide. [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.

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[NIH]

Womb: A hollow, thick-walled, muscular organ in which the impregnated ovum is developed into a child. [NIH] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] X-ray therapy: The use of high-energy radiation from x-rays to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. X-ray therapy is also called radiation therapy, radiotherapy, and irradiation. [NIH] 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] Zygote: The fertilized ovum. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]

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INDEX A Abdominal, 26, 46, 67, 88, 106, 159, 169, 174, 195 Abortion, 159, 163 Abscess, 51, 159, 205 Acceptor, 159, 188, 195, 211 Acetylcholine, 159, 193 Acetylgalactosamine, 159, 182 Acetylglucosamine, 159, 182 Acidity, 159, 197 Actin, 159, 192, 211 Acute myeloid leukemia, 159, 200 Adaptation, 101, 159 Adjustment, 94, 159 Adrenergic, 111, 159, 163, 175, 178 Adrenergic Agonists, 111, 159 Adverse Effect, 159, 171, 206 Aerobic, 159, 179 Aerosol, 99, 160 Affinity, 12, 91, 160, 171, 206 Age-Adjusted, 4, 160 Agonist, 7, 160, 175, 178, 208 Albumin, 50, 96, 160, 198 Aldehydes, 91, 160 Algorithms, 17, 160, 166 Alkaline, 160, 167, 195 Allogeneic, 160, 182 Alpha Particles, 160, 202 Alternative medicine, 115, 160 Alveoli, 160, 213 Amino Acid Sequence, 98, 161, 162, 182 Amnion, 161 Amniotic Fluid, 105, 161 Amplification, 18, 161 Ampulla, 161, 177 Amyloid, 161, 169 Anaesthesia, 161, 186 Anal, 161, 180 Analogous, 95, 161, 211 Analytes, 8, 161, 208 Anaplasia, 161 Anemia, 111, 161, 181, 197 Anesthesia, 26, 60, 111, 161, 164, 177, 193, 200 Aneurysm, 63, 65, 161, 212 Angina, 6, 91, 92, 104, 107, 108, 161 Angina Pectoris, 107, 108, 161 Angiogenesis, 22, 96, 161, 190

Angiogram, 33, 156, 161 Angiography, 11, 13, 14, 15, 16, 17, 18, 32, 33, 34, 35, 44, 54, 57, 61, 63, 64, 66, 73, 99, 156, 157, 161 Angioplasty, 19, 85, 92, 95, 107, 108, 161, 164 Angiotensinogen, 162, 203 Animal model, 6, 22, 162 Anions, 160, 162, 187 Ankle, 93, 162, 212, 213 Antagonism, 162, 171 Anterior Cerebral Artery, 162, 169 Antibodies, 21, 83, 84, 162, 163, 183, 185, 189, 191, 198 Antibodies, Anticardiolipin, 162, 163 Antibodies, Antiphospholipid, 162, 163 Anticoagulant, 4, 6, 11, 18, 39, 75, 76, 88, 133, 141, 162, 163, 200, 213 Antidote, 6, 162 Antigen, 85, 160, 162, 168, 172, 185, 186, 190, 208 Anti-infective, 162, 184 Anti-inflammatory, 100, 162, 164 Anti-Inflammatory Agents, 163, 164 Antioxidant, 163, 195 Antiphospholipid Syndrome, 49, 162, 163 Antiplasmin, 101, 163 Antipsychotic, 163, 171, 193 Antithrombotic, 5, 10, 18, 106, 136, 137, 140, 141, 144, 145, 163 Antiviral, 163, 196 Anus, 161, 163, 166, 171, 186 Anxiety, 155, 163, 196 Aorta, 63, 163, 168, 173, 175, 213 Aortic Valve, 36, 163 Apoptosis, 9, 163 Applicability, 13, 15, 16, 17, 18, 43, 164 Aqueous, 164, 165, 174, 177, 184, 188 Arachidonic Acid, 7, 164, 188, 200 Arginine, 164, 193, 211, 212 Arterial, 5, 6, 8, 9, 22, 57, 82, 85, 86, 88, 91, 92, 96, 97, 99, 102, 104, 163, 164, 169, 185, 201, 208 Arteries, 7, 84, 86, 93, 98, 105, 106, 108, 146, 163, 164, 166, 173, 187, 190, 192, 202, 209 Arteriography, 26, 164 Arterioles, 164, 166, 167, 192

Pulmonary embolism

Arteriosclerosis, 164, 169, 192 Arteriosus, 164, 201 Arteriovenous, 164, 169 Arthroplasty, 36, 40, 41, 42, 63, 68, 73, 88, 106, 164 Aspiration, 111, 164 Aspirin, 10, 88, 114, 133, 164 Assay, 22, 26, 38, 46, 57, 64, 70, 81, 84, 164, 185 Asymptomatic, 28, 90, 164 Atherectomy, 164, 177 Atrial, 40, 42, 49, 50, 51, 56, 70, 135, 164, 213 Atrial Fibrillation, 70, 135, 164, 213 Atrium, 164, 168, 213 Attenuation, 86, 164 Atypical, 114, 165, 171 B Bacteremia, 51, 165 Bacteria, 162, 165, 172, 176, 177, 178, 190, 191, 205, 207, 210, 212 Bacterial Physiology, 159, 165 Bacterium, 165, 172, 183 Basal Ganglia, 163, 165, 169 Base, 165, 174, 182, 187, 209 Basophils, 165, 188 Benign, 52, 165, 192, 202 Bile, 165, 181, 188 Bilirubin, 160, 165 Binding Sites, 12, 165 Bioassays, 22, 165 Bioavailability, 10, 165 Biochemical, 10, 19, 29, 82, 85, 165, 182, 205 Biomarkers, 30, 165 Biomolecular, 165, 208 Biopsy, 165, 196 Biotechnology, 24, 25, 96, 115, 127, 165 Bladder, 87, 166, 193, 200, 212 Bleeding Time, 10, 166 Blood Cell Count, 166, 197 Blood Coagulation, 19, 88, 104, 105, 166, 167 Blood Coagulation Factors, 166 Blood Platelets, 166, 205, 209 Blood pressure, 5, 166, 168, 185, 191, 194, 197, 202, 206 Blood Substitutes, 95, 166, 181 Blood Volume, 49, 166 Body Fluids, 165, 166, 167, 206, 211 Bolus, 114, 166 Bolus infusion, 166

216

Bone Marrow, 84, 105, 159, 166, 185, 189, 192, 200, 206 Bone scan, 166, 204 Bowel, 161, 166, 174, 193, 207 Bowel Movement, 166, 174, 207 Brachytherapy, 166, 186, 187, 202, 214 Bradykinin, 167, 193, 198 Branch, 153, 167, 189, 196, 206, 209, 210 Breakdown, 106, 167, 174, 181 Bronchi, 167, 178, 211 Bronchial, 30, 107, 108, 167 Bronchitis, 100, 107, 108, 167, 170 Bupivacaine, 167, 188 Bypass, 85, 91, 92, 104, 167, 209 C Calcification, 48, 164, 167 Calcium, 20, 115, 167, 171, 190, 191, 201, 211 Calcium blocker, 115, 167 Calpain, 20, 167 Capillary, 82, 166, 167, 213 Carbohydrate, 167, 182, 199 Carbon Dioxide, 95, 105, 166, 167, 180, 181, 185, 204, 213 Carcinogenesis, 168, 170 Carcinogenic, 168, 186 Carcinoma, 67, 168 Cardiac, 5, 19, 24, 30, 31, 34, 37, 47, 49, 53, 54, 60, 91, 92, 104, 107, 108, 164, 167, 168, 173, 176, 178, 183, 188, 192, 195, 204, 206, 208 Cardiac arrest, 53, 168, 208 Cardiac Output, 168, 206 Cardiolipins, 163, 168 Cardiology, 32, 46, 58, 60, 62, 69, 73, 134, 135, 140, 141, 145, 168 Cardiopulmonary, 19, 20, 25, 27, 53, 168 Cardiopulmonary Bypass, 19, 25, 168 Cardiopulmonary Resuscitation, 53, 168 Cardiorespiratory, 11, 168 Cardiovascular, 5, 10, 11, 12, 26, 40, 54, 57, 62, 83, 84, 85, 86, 90, 91, 92, 103, 104, 135, 144, 168, 179, 188, 205 Cardiovascular disease, 11, 12, 83, 85, 90, 103, 104, 168 Cardiovascular Physiology, 5, 168 Cardiovascular System, 168 Carrier Proteins, 168, 198 Case report, 27, 40, 51, 55, 168 Case series, 38, 168 Case-Control Studies, 8, 168 Catecholamine, 169, 175, 197

217

Catheter, 33, 42, 54, 83, 86, 99, 114, 140, 164, 169, 177 Catheterization, 162, 169 Cations, 169, 187 Caudal, 169, 199 Cause of Death, 85, 90, 169 Cell Adhesion, 18, 169 Cell Adhesion Molecules, 18, 169 Cell Death, 163, 169 Cell Division, 84, 165, 169, 191, 198 Central Nervous System, 82, 159, 169, 171, 182, 188, 205 Cerebral, 85, 92, 97, 107, 108, 134, 162, 165, 169, 173, 177, 178, 181, 189 Cerebral Angiography, 169, 189 Cerebral Hemorrhage, 107, 108, 169 Cerebral Infarction, 85, 169 Cerebrovascular, 82, 91, 104, 168, 169 Cerebrum, 169 Cesarean Section, 45, 169 Character, 161, 169 Chemokines, 22, 170 Chemopreventive, 21, 170 Chest Pain, 135, 139, 145, 170 Chin, 170, 190 Cholesterol, 165, 170, 173, 208 Chromatin, 163, 170, 178 Chromosomal, 161, 170 Chromosome, 170, 172, 188 Chronic, 3, 12, 18, 30, 34, 85, 93, 106, 132, 139, 141, 142, 145, 146, 170, 175, 186, 187, 199, 207, 208 Chronic Disease, 13, 170 Chronic Obstructive Pulmonary Disease, 139, 145, 170 Circadian, 5, 170 Circadian Rhythm, 5, 170 Circulatory system, 13, 170 CIS, 9, 170, 204 Cleave, 14, 170 Clinical Medicine, 47, 170, 199 Clinical trial, 4, 9, 10, 17, 75, 77, 127, 170, 201, 203 Clitoral, 108, 170 Clone, 84, 170 Cloning, 166, 171 Clot Retraction, 171, 198 Clozapine, 29, 31, 171 Coagulation, 4, 6, 19, 45, 81, 85, 88, 89, 96, 98, 103, 104, 105, 163, 166, 171, 183, 198, 209, 213 Cofactor, 4, 11, 171, 201

Collagen, 10, 20, 160, 171, 173, 179, 180, 190, 198, 200 Collapse, 167, 171 Colloidal, 160, 171, 176 Colon, 59, 143, 171, 187, 188 Comorbidity, 4, 171 Complement, 171, 198 Computational Biology, 127, 172 Computerized tomography, 172 Conception, 159, 172, 180 Conduction, 172, 193 Cone, 98, 172 Confidence Intervals, 4, 172 Congestive heart failure, 105, 138, 172 Conjugated, 172 Conjugation, 22, 172 Connective Tissue, 163, 166, 171, 173, 180, 208 Connective Tissue Diseases, 163, 173 Consciousness, 173, 175, 204 Constriction, 173, 187, 212 Constriction, Pathologic, 173, 212 Contraindications, ii, 173 Contrast Media, 173, 189 Contrast medium, 32, 161, 169, 173 Conus, 173, 201 Convulsions, 173, 176, 199 Coronary, 4, 6, 9, 21, 37, 48, 54, 82, 85, 107, 108, 136, 161, 168, 173, 184, 190, 192 Coronary Artery Bypass, 6, 54, 107, 108, 173 Coronary Circulation, 161, 173 Coronary Disease, 85, 173 Coronary heart disease, 9, 21, 168, 173 Coronary Thrombosis, 173, 190, 192 Coronary Vessels, 173 Corpus, 111, 173, 196 Cortisol, 160, 173 Criterion, 20, 174 Curative, 174, 209 Cyclic, 167, 174, 183, 194 Cyst, 27, 174 Cystathionine beta-Synthase, 174, 184 Cytokines, 100, 170, 174 Cytoplasm, 163, 165, 174, 178, 192 Cytoprotection, 9, 174 D Defense Mechanisms, 105, 174 Deletion, 163, 174 Density, 7, 174, 194 Dermatitis, 174, 199 Deuterium, 174, 184

Pulmonary embolism

Diagnostic procedure, 79, 102, 115, 174 Dialyzer, 174, 183 Diaphragm, 174, 199 Diastolic, 174, 185 Digestion, 165, 166, 174, 188, 196, 207 Digestive system, 78, 174 Dihydroergotamine, 88, 174 Dihydrotestosterone, 174, 203 Dilatation, 30, 159, 161, 174, 175, 186, 212 Dilatation, Pathologic, 175, 212 Dilation, 108, 164, 167, 175, 212 Dilution, 81, 175, 178 Direct, iii, 18, 81, 85, 102, 117, 170, 175, 184, 203, 208 Disease Progression, 19, 175 Dislocation, 48, 175 Dissection, 46, 175 Dissociation, 160, 175 Distal, 83, 86, 92, 108, 173, 175, 176, 201 Dopamine, 163, 171, 175, 193, 197 Dorsal, 175, 199 Dosimetry, 10, 175 Double Outlet Right Ventricle, 26, 175 Drug Interactions, 120, 175 Drug Tolerance, 175, 210 Duodenum, 165, 176, 177, 196, 207 Dysmenorrhea, 107, 108, 176 E Echocardiography, 20, 24, 36, 42, 48, 49, 50, 57, 69, 176 Eclampsia, 107, 108, 176, 199 Ectopia Lentis, 82, 176 Edema, 18, 89, 93, 106, 176, 199, 213 Effector, 22, 159, 171, 176 Efficacy, 10, 18, 37, 75, 76, 176 Elastic, 80, 83, 86, 176 Elastin, 171, 173, 176, 179 Elective, 48, 106, 176 Electric shock, 168, 176 Electrocoagulation, 171, 176 Electrode, 73, 89, 94, 176 Electrolyte, 176, 206 Electrophoresis, 20, 82, 176, 185 Elementary Particles, 176, 189, 193, 201 Embolectomy, 64, 176, 209 Emboli, 72, 73, 93, 97, 106, 110, 111, 114, 134, 139, 142, 176, 213 Embolization, 72, 73, 111, 176, 213 Embolus, 38, 92, 98, 105, 106, 146, 177, 186 Embryo, 159, 161, 177, 180, 186 Emphysema, 100, 170, 177 Emulsion, 177, 180

218

Encephalocele, 177, 193 Endarterectomy, 107, 108, 162, 164, 177 Endogenous, 97, 101, 107, 166, 167, 175, 177, 211 Endonucleases, 6, 177 Endoscope, 177 Endoscopic, 56, 177 Endothelial cell, 7, 8, 12, 18, 86, 177, 211 Endothelins, 55, 177 Endothelium, 7, 10, 85, 107, 177, 178, 193, 198, 211 Endothelium, Lymphatic, 177 Endothelium, Vascular, 177 Endothelium-derived, 107, 178, 193 Endotoxin, 100, 178 Environmental Health, 126, 128, 178 Enzymatic, 54, 161, 167, 172, 178, 180, 204 Enzyme Inhibitors, 178, 198 Eosinophils, 178, 188 Epidemiological, 5, 12, 178 Epidermis, 178, 202 Epinephrine, 159, 175, 178, 193, 194, 212 Epithelium, 177, 178 Epitope, 22, 85, 178 Erectile, 178, 196 Erection, 108, 111, 178, 200 Ergotamine, 174, 178 Erythrocyte Volume, 166, 178 Erythrocytes, 105, 161, 166, 167, 178, 203 Esophageal, 73, 178, 205 Esophageal Varices, 178, 205 Esophagus, 174, 178, 179, 196, 207 Estrogen, 21, 179, 205, 208 Eukaryotic Cells, 82, 179, 194 Excitation, 102, 179, 193 Exercise Test, 27, 179 Exogenous, 22, 101, 177, 179 External-beam radiation, 179, 187, 202, 214 Extracellular, 20, 161, 173, 179, 180, 190, 191, 206 Extracellular Matrix, 173, 179, 180, 190 Extracellular Matrix Proteins, 179, 190 Extraction, 73, 169, 179 Extremity, 87, 89, 90, 106, 114, 135, 138, 179, 205 F Family Planning, 127, 179 Fat, 67, 105, 164, 166, 173, 176, 177, 179, 188, 206 Fatigue, 179, 183 Fatty acids, 160, 179, 200, 209

219

Femoral, 33, 65, 115, 168, 179, 180, 184, 199 Femoral Artery, 168, 179, 180 Femoral Neck Fractures, 179, 184 Femoral Vein, 65, 180, 199 Femur, 179, 180, 184 Fetal Development, 180, 193 Fetus, 9, 159, 169, 180, 212 Fibrin, 8, 9, 14, 19, 41, 59, 81, 84, 85, 91, 92, 96, 97, 104, 105, 163, 166, 171, 180, 198, 209, 210 Fibrinogen, 8, 27, 66, 81, 85, 104, 180, 198, 209 Fibrinolysis, 14, 19, 101, 180 Fibrinolytic, 14, 18, 97, 111, 180, 209 Fibrinolytic Agents, 14, 18, 180, 209 Fibroblasts, 86, 180 Fibrosis, 82, 100, 103, 132, 180, 205 Fibula, 180, 199 Filtration, 92, 180 Fistula, 111, 180 Fixation, 103, 180 Flank Pain, 26, 180 Flatus, 181 Fluorescence, 12, 181 Fluorocarbons, 95, 181 Folate, 181 Fold, 92, 181, 195 Folic Acid, 9, 181 Foramen, 53, 170, 181 Forearm, 166, 181 Fossa, 94, 181 Fovea, 180, 181 Friction, 181, 188 Frontal Lobe, 162, 169, 181 Fungi, 172, 181, 182, 190, 191, 214 G Gallbladder, 159, 174, 181 Gangrene, 111, 181 Gas, 24, 94, 95, 99, 102, 167, 181, 184, 193, 194, 202, 204, 208, 213 Gas exchange, 24, 99, 181, 204, 213 Gastric, 56, 181, 196, 205 Gastrin, 181, 184 Gastrointestinal, 107, 108, 167, 178, 181, 188, 205, 207, 211 Gastrointestinal tract, 181, 188, 205, 207, 211 Gene, 101, 166, 181 Generator, 89, 99, 181 Genetic Code, 182, 194 Genetic Markers, 8, 182 Genetics, 43, 172, 182

Genital, 108, 182 Genotype, 19, 182, 197 Germfree, 84, 182 Glomerulus, 182, 192 Glucuronic Acid, 182, 183 Glutamic Acid, 181, 182, 193, 200 Glycine, 160, 182, 193, 205 Glycoprotein, 10, 18, 163, 180, 182 Glycosaminoglycans, 4, 179, 182 Glycosylation, 12, 182 Governing Board, 182, 199 Gp120, 182, 196 Graft, 6, 54, 107, 108, 182 Graft Rejection, 107, 108, 182 Grafting, 173, 182 Grasses, 181, 182 Growth, 91, 104, 105, 107, 108, 161, 162, 163, 169, 180, 182, 189, 192, 198, 205, 210, 211 Guanylate Cyclase, 183, 194 H Haptens, 160, 183 Heart Arrest, 168, 183 Heart attack, 6, 13, 91, 92, 104, 105, 168, 183 Heart failure, 30, 134, 140, 183 Heartbeat, 183, 208 Hematology, 10, 35, 44, 55, 110, 183 Heme, 8, 100, 165, 183, 195 Hemodialysis, 111, 174, 183 Hemodynamics, 106, 183 Hemoglobin, 161, 166, 178, 183, 195 Hemolytic, 183, 207 Hemorrhage, 42, 166, 176, 183, 202, 207 Hemorrhoids, 183, 205 Hemostasis, 39, 53, 85, 92, 96, 102, 104, 183, 205 Heparin, 4, 10, 23, 42, 45, 51, 52, 54, 63, 64, 67, 76, 88, 91, 92, 103, 104, 114, 118, 140, 183 Hepatic, 25, 160, 183 Heredity, 181, 182, 184 Heterogeneity, 160, 184 Hip Fractures, 45, 180, 184 Homeostasis, 100, 184 Homotypic, 19, 184 Hormonal, 108, 184 Hormone, 8, 142, 165, 170, 173, 178, 181, 184, 209, 210 Hormone Replacement Therapy, 8, 142, 184 Hospital Mortality, 60, 184

Pulmonary embolism

Humoral, 182, 184 Hybrid, 84, 170, 184 Hybridoma, 84, 184 Hydrogen, 90, 101, 159, 165, 167, 174, 179, 181, 184, 188, 191, 193, 195, 197, 201 Hydrogen Peroxide, 90, 101, 184, 188 Hydrogenation, 174, 184 Hydrolysis, 177, 184, 201, 211 Hydroxylysine, 171, 184 Hydroxyproline, 160, 171, 184 Hyperhomocysteinemia, 46, 61, 82, 174, 184 Hyperoxia, 101, 184 Hypertension, 12, 85, 100, 107, 108, 132, 168, 169, 185, 199 Hyperventilation, 105, 185 Hypotension, 53, 163, 173, 185 Hypoxia, 50, 185 Hypoxic, 19, 185 Hysterotomy, 169, 185 I Id, 74, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 152, 154, 185 Idiopathic, 90, 100, 185 Iliac Vein, 180, 185 Immune response, 162, 182, 183, 185 Immunization, 185, 200 Immunoassay, 59, 81, 84, 162, 185 Immunoelectrophoresis, 163, 185 Immunoglobulin, 61, 84, 162, 185, 191 Immunologic, 185, 203 Immunology, 160, 185 Impairment, 185, 190, 213 Implant radiation, 185, 186, 187, 202, 214 Impotence, 111, 178, 185 In vitro, 4, 8, 10, 19, 22, 81, 84, 85, 101, 185 In vivo, 5, 8, 10, 22, 84, 85, 97, 101, 183, 185, 209 Incision, 185, 187 Indicative, 10, 81, 109, 186, 196, 212 Induction, 9, 101, 163, 186 Infarction, 5, 11, 12, 21, 42, 51, 81, 83, 84, 85, 91, 92, 96, 97, 101, 104, 107, 134, 141, 169, 173, 186, 190, 192, 203, 213 Infection, 48, 84, 105, 186, 189, 207, 213 Inferior vena cava, 25, 62, 80, 84, 86, 98, 185, 186, 213 Infusion, 46, 186, 205 Inhalation, 102, 119, 160, 186 Initiation, 18, 105, 186, 211 Inlay, 186, 204

220

Innervation, 186, 197, 205, 210 Insight, 5, 19, 186 Intermittent, 12, 87, 186 Internal Medicine, 4, 8, 23, 31, 33, 35, 36, 37, 39, 42, 44, 47, 52, 61, 65, 66, 68, 72, 183, 186 Internal radiation, 186, 187, 202, 214 Interstitial, 100, 166, 186, 187, 192, 214 Intestines, 159, 181, 186 Intracellular, 186, 194 Intracranial Aneurysm, 169, 186 Intramuscular, 90, 186 Intravascular, 22, 45, 81, 96, 140, 186 Intravenous, 17, 42, 52, 61, 64, 90, 102, 186, 187 Intrinsic, 5, 20, 104, 160, 187 Invasive, 9, 11, 17, 18, 22, 26, 57, 87, 99, 104, 105, 187, 189, 195 Invertebrates, 4, 187 Ions, 90, 159, 165, 175, 176, 184, 187, 201 Irradiation, 101, 187, 214 Ischemia, 20, 187, 203 Ischemic stroke, 136, 187 J Joint, 36, 48, 49, 63, 74, 164, 187, 189, 208 K Kb, 126, 187 Kidney Disease, 3, 78, 100, 126, 141, 187 Kidney stone, 187, 212 Kinetic, 19, 187 L Large Intestine, 174, 186, 187, 203, 206 Larynx, 100, 187, 210 Latency, 21, 187 Latent, 14, 187 Lavage, 30, 188 Lens, 176, 188 Lepirudin, 54, 188 Lethal, 26, 51, 188 Leukemia, 61, 159, 188 Leukocytes, 7, 22, 165, 166, 170, 174, 178, 188, 192 Leukotrienes, 164, 188 Library Services, 152, 188 Lidocaine, 88, 188 Ligaments, 173, 188 Ligands, 169, 188, 208 Linkage, 182, 188 Lipid, 21, 164, 188, 195 Lipid Peroxidation, 188, 195 Lipopolysaccharide, 101, 188 Liver scan, 188, 204

221

Liver Transplantation, 36, 37, 188 Lobe, 162, 169, 188, 196 Localized, 12, 108, 159, 180, 186, 188, 198, 205, 209, 212 Loop, 12, 94, 188 Lubricants, 188, 189 Lubrication, 108, 188 Lumbar, 189, 205, 210 Lung Transplantation, 8, 189 Lupus, 162, 163, 189, 208 Luxation, 175, 189 Lymph, 170, 177, 189 Lymphatic, 177, 186, 189, 206, 207 Lymphatic system, 189, 206, 207 Lymphocyte, 162, 189, 190 Lymphoid, 162, 189 Lytic, 98, 189, 205 M Magnetic Resonance Angiography, 42, 189 Magnetic Resonance Imaging, 22, 56, 102, 189, 204 Magnetic Resonance Spectroscopy, 5, 189 Malignancy, 23, 77, 82, 105, 106, 189 Malignant, 33, 84, 189, 192, 202 Malnutrition, 160, 189 Mammary, 173, 189, 208 Mammogram, 167, 189, 191 Manifest, 22, 189 Matrix metalloproteinase, 20, 189 Mechanical ventilation, 137, 190 Medial, 164, 190, 210 Mediate, 9, 18, 169, 175, 190 Mediator, 7, 22, 190, 205 MEDLINE, 127, 190 Megaloblastic, 181, 190 Melanin, 190, 197, 212 Meninges, 169, 190 Menopause, 135, 190, 199 Menstruation, 176, 190 Mental, iv, 4, 78, 82, 126, 128, 136, 170, 175, 179, 190, 200, 201 Mental Disorders, 78, 190, 200, 201 Mental Health, iv, 4, 78, 126, 128, 190, 200 Mental Retardation, 82, 190 Meta-Analysis, 52, 53, 190 Metastasis, 96, 169, 190 Methionine, 190, 208 MI, 21, 62, 85, 157, 190 Microbe, 190, 210 Microbiology, 159, 165, 191 Microcalcifications, 167, 191

Microorganism, 171, 191, 213 Micro-organism, 182, 191 Microspheres, 96, 97, 191 Migration, 84, 86, 98, 99, 191, 213 Mitogen-Activated Protein Kinase Kinases, 191 Mitogen-Activated Protein Kinases, 8, 191 Mitosis, 163, 191 Modification, 161, 191 Monitor, 84, 99, 191, 194 Monoclonal, 12, 22, 83, 84, 187, 191, 202, 214 Monoclonal antibodies, 12, 84, 191 Monocytes, 7, 188, 192 Mononuclear, 192 Monotherapy, 38, 192 Morphology, 183, 192 Muscle Contraction, 94, 192 Muscle Relaxation, 192, 193 Musculoskeletal System, 192, 195 Mydriatic, 175, 192 Myeloma, 84, 184, 192 Myocardial Ischemia, 161, 173, 192 Myocardium, 161, 190, 192 Myofibrils, 167, 192 Myosin, 192, 211 N NCI, 1, 77, 125, 170, 192 Need, 3, 6, 11, 14, 17, 22, 93, 110, 120, 121, 147, 159, 190, 192, 210 Neoplasia, 192 Neoplasm, 192, 211 Neoplastic, 81, 161, 192 Nephritis, 107, 108, 192 Nephropathy, 187, 192 Nerve, 90, 93, 96, 159, 161, 170, 186, 190, 193, 197, 199, 200, 204, 205, 207, 210, 211, 212 Nerve Regeneration, 96, 193 Nervous System, 169, 190, 193 Neural, 9, 46, 161, 177, 184, 193 Neural tube defects, 9, 193 Neuroleptic, 163, 171, 193 Neurologic, 89, 111, 177, 193 Neuromuscular, 89, 138, 159, 193 Neuromuscular Blockade, 138, 193 Neuromuscular Junction, 159, 193 Neuropeptides, 167, 193 Neurotransmitter, 159, 161, 167, 175, 182, 193, 194 Neutralization, 6, 193 Neutrons, 160, 187, 193, 202

Pulmonary embolism

Neutrophil, 19, 22, 105, 193 Nitric Oxide, 49, 82, 107, 193 Nitrogen, 82, 179, 180, 181, 194, 211 Noble Gases, 102, 194 Nonmalignant, 21, 194 Norepinephrine, 159, 175, 193, 194 Normotensive, 20, 31, 67, 194 Nuclear, 5, 37, 41, 49, 54, 63, 69, 99, 144, 165, 172, 179, 194, 212 Nuclear Medicine, 37, 41, 49, 54, 63, 69, 99, 144, 194 Nuclei, 160, 162, 172, 189, 191, 193, 194, 201 Nucleic acid, 6, 182, 194 Nucleus, 162, 163, 165, 170, 174, 176, 178, 179, 192, 193, 194, 201 O Observational study, 38, 194 Odds Ratio, 194, 203 Opacity, 174, 194 Ophthalmology, 180, 194 Organelles, 174, 192, 194 Orgasm, 108, 195 Orthopaedic, 41, 73, 103, 142, 195 Osmotic, 160, 195 Osteoporosis, 55, 82, 141, 142, 195 Outpatient, 11, 60, 195 Oxidation, 91, 159, 163, 188, 195 Oxidative Stress, 100, 101, 195 Oxides, 82, 195 Oximetry, 67, 195 Oxygen Consumption, 179, 195, 204 Oxygenase, 8, 100, 195 Oxygenator, 168, 195 P Pacemaker, 25, 49, 195 Paediatric, 40, 195 Palliative, 142, 195, 209 Pancreas, 159, 165, 174, 195, 211 Panic, 105, 196 Paradoxical, 53, 196 Parietal, 162, 196, 199 Paroxysmal, 161, 196 Pathogenesis, 8, 10, 11, 19, 86, 102, 196 Pathologic, 81, 85, 163, 165, 173, 196 Pathologic Processes, 163, 196 Pathophysiology, 22, 27, 55, 111, 196 Pelvic, 88, 196, 200 Pelvis, 80, 186, 187, 189, 196, 212 Penis, 108, 111, 196, 197, 200 Peptic, 196, 205 Peptic Ulcer, 196, 205

222

Peptic Ulcer Hemorrhage, 196, 205 Peptide, 10, 20, 30, 38, 52, 59, 68, 85, 160, 196, 200, 201 Peptide T, 68, 196 Perception, 172, 196 Percutaneous, 6, 26, 28, 62, 99, 196 Perforation, 181, 196 Perfusion, 13, 14, 15, 16, 17, 26, 33, 37, 41, 42, 49, 50, 54, 58, 68, 69, 95, 99, 100, 102, 134, 185, 196 Perioperative, 60, 114, 135, 196 Peripheral Vascular Disease, 6, 13, 100, 196 Pernicious, 61, 190, 197 Pernicious anemia, 61, 197 Peroneal Nerve, 89, 197, 205 PH, 49, 197 Phallic, 180, 197 Pharmacokinetic, 91, 197 Pharmacologic, 161, 197, 210 Pharmacotherapy, 61, 67, 111, 197 Phenotype, 19, 197 Phenylalanine, 197, 211 Phlebitis, 84, 86, 197 Phospholipids, 162, 163, 168, 179, 197, 201 Phosphorus, 167, 197 Phosphorylase, 167, 197 Phosphorylation, 20, 191, 197, 201 Photocoagulation, 171, 197 Physiologic, 14, 22, 160, 180, 190, 197, 203 Physiology, 10, 55, 168, 183, 198 Plants, 167, 192, 194, 198, 210 Plaque, 161, 164, 198 Plasma cells, 162, 192, 198 Plasma protein, 85, 97, 160, 177, 198, 201 Plasmin, 14, 81, 97, 101, 163, 180, 198, 210, 212 Plasminogen, 13, 66, 81, 96, 97, 163, 180, 198, 207, 210, 212 Plasminogen Activators, 198 Platelet Activation, 10, 83, 198 Platelet Aggregation, 7, 10, 92, 107, 108, 193, 198, 209 Platelets, 7, 10, 12, 18, 19, 83, 86, 88, 92, 96, 105, 167, 194, 198, 209 Platinum, 188, 198 Pleura, 198, 199 Pleural, 29, 198, 199 Pleural cavity, 199 Pleural Effusion, 29, 199 Pneumonia, 100, 105, 107, 108, 173, 199 Polymers, 5, 81, 84, 199, 201

223

Polysaccharide, 162, 199 Popliteal, 94, 180, 199 Popliteal Vein, 180, 199 Posterior, 90, 161, 164, 175, 195, 199 Postmenopausal, 142, 195, 199 Postoperative, 36, 39, 73, 88, 106, 138, 199 Postphlebitic Syndrome, 101, 199 Post-traumatic, 106, 199 Practice Guidelines, 128, 134, 135, 138, 199 Precancerous, 170, 199 Preclinical, 6, 199 Precursor, 162, 164, 175, 176, 178, 194, 197, 198, 199, 201, 211, 212 Preeclampsia, 107, 108, 199 Pre-eclamptic, 176, 199 Prevalence, 46, 48, 60, 106, 114, 194, 199 Priapism, 110, 111, 145, 200 Primary Prevention, 13, 23, 142, 200 Primary tumor, 84, 200 Procaine, 188, 200 Proenzymes, 104, 200 Progeny, 172, 200 Progression, 12, 162, 200 Progressive, 91, 175, 182, 198, 200, 211 Projection, 174, 194, 200 Proline, 171, 184, 200 Promyelocytic leukemia, 61, 200 Prone, 90, 200 Prophylaxis, 22, 63, 72, 73, 85, 88, 144, 200, 213 Proportional, 81, 200, 208 Prospective Studies, 23, 200 Prospective study, 7, 11, 39, 49, 69, 200 Prostaglandins, 164, 200 Prostate, 144, 165, 200, 211 Protease, 20, 104, 200, 210 Protein C, 121, 160, 161, 200, 201, 211 Protein Conformation, 161, 201 Protein Kinase C, 191, 201 Protein S, 166, 182, 201 Protein-Serine-Threonine Kinases, 191, 201 Proteinuria, 199, 201 Proteolytic, 20, 81, 97, 104, 172, 180, 198, 201, 210, 212 Prothrombin, 8, 21, 104, 201, 209 Protocol, 5, 15, 16, 17, 55, 201 Protons, 160, 184, 189, 201, 202 Protozoa, 172, 191, 201 Proximal, 84, 86, 89, 92, 108, 114, 175, 201, 205 Psychiatry, 29, 180, 201, 213

Psychic, 190, 201 Public Policy, 127, 201 Pulmonary Artery, 13, 14, 15, 16, 17, 18, 99, 106, 166, 175, 201, 202, 213 Pulmonary Circulation, 98, 99, 202 Pulmonary Edema, 8, 36, 202 Pulmonary hypertension, 7, 82, 100, 101, 202 Pulmonary Ventilation, 102, 185, 202, 204 Pulse, 20, 67, 89, 191, 195, 202 Pupil, 175, 192, 202 Purpura, 61, 202 Putrefaction, 181, 202 Q Quantitative Structure-Activity Relationship, 96, 202 R Race, 191, 202 Radiation, 10, 62, 161, 176, 179, 181, 186, 187, 189, 202, 204, 214 Radiation therapy, 179, 186, 187, 202, 214 Radioactive, 99, 166, 184, 185, 186, 187, 188, 191, 194, 202, 204, 208, 212, 214 Radiography, 69, 132, 161, 169, 173, 202 Radiolabeled, 187, 202, 214 Radiological, 72, 132, 196, 202 Radiopharmaceutical, 72, 182, 202 Radiotherapy, 166, 187, 202, 214 Randomized, 52, 176, 203 Receptor, 7, 10, 19, 72, 88, 107, 159, 162, 171, 172, 175, 182, 196, 201, 203, 205 Recombinant, 12, 41, 97, 203 Recombination, 172, 182, 203 Rectum, 163, 166, 171, 174, 181, 187, 200, 203 Recurrence, 75, 134, 170, 203 Red blood cells, 178, 183, 195, 203 Reductase, 21, 203 Refer, 1, 171, 180, 181, 188, 193, 203, 210 Refractory, 67, 176, 203 Regimen, 176, 197, 203 Relative risk, 4, 203 Remission, 203 Renal Dialysis, 91, 104, 203 Renin, 107, 162, 203 Reperfusion, 8, 20, 203 Reperfusion Injury, 203 Resection, 60, 203 Respiration, 27, 28, 44, 50, 68, 167, 191, 204 Respirator, 190, 204, 213 Respiratory distress syndrome, 100, 204 Respiratory Physiology, 43, 59, 204, 213

Pulmonary embolism

Respiratory System, 105, 204 Restoration, 20, 203, 204, 214 Resuscitation, 37, 53, 64, 168, 204 Retina, 173, 188, 204 Retinal, 172, 204 Retrospective, 43, 204 Risk factor, 4, 8, 9, 12, 21, 23, 63, 89, 184, 200, 203, 204 Rod, 103, 165, 204 S Salivary, 174, 204 Salivary glands, 174, 204 Saphenous, 173, 204 Saphenous Vein, 173, 204 Sarcomere, 20, 204 Scans, 11, 14, 15, 16, 17, 28, 30, 204 Sciatic Nerve, 197, 205, 210 Sclerotherapy, 56, 205 Screening, 20, 95, 102, 115, 133, 170, 205 Secondary tumor, 190, 205 Secretion, 170, 205 Selective estrogen receptor modulator, 205, 208 Senile, 195, 205 Sensor, 99, 205 Sepsis, 100, 105, 106, 205 Septal, 40, 50, 51, 162, 175, 205 Septic, 51, 82, 100, 205 Sequela, 18, 205 Sequence Homology, 196, 205 Serine, 174, 191, 201, 205, 210, 211 Serologic, 185, 205 Serotonin, 163, 171, 193, 197, 205, 211 Serous, 177, 198, 205 Serum, 20, 160, 171, 205 Shock, 20, 37, 53, 65, 82, 100, 107, 108, 205, 206, 211 Shock, Cardiogenic, 82, 206 Side effect, 5, 117, 121, 159, 163, 206, 210 Signs and Symptoms, 105, 203, 206 Skeletal, 20, 82, 192, 206, 211 Skeleton, 159, 180, 187, 206 Skull, 177, 193, 206, 209 Small intestine, 176, 184, 186, 206, 211 Smooth muscle, 7, 86, 107, 108, 167, 206 Sodium, 73, 91, 121, 206 Soft tissue, 166, 206 Solid tumor, 161, 206 Solvent, 12, 195, 206 Specialist, 147, 175, 206 Species, 82, 160, 178, 184, 191, 202, 205, 206, 207, 211, 213, 214

224

Specificity, 13, 14, 15, 16, 17, 22, 64, 81, 160, 206 Spectroscopic, 102, 189, 206 Sphincter, 187, 206 Spina bifida, 193, 206 Spinal cord, 89, 106, 143, 169, 170, 190, 193, 200, 205, 207 Spleen, 84, 95, 100, 184, 189, 207 Stabilization, 85, 143, 207 Staging, 204, 207 Stasis, 18, 88, 114, 199, 207, 213 Statistically significant, 4, 207 Steady state, 87, 207 Stent, 98, 207 Stimulus, 176, 179, 186, 187, 207, 209 Stomach, 159, 174, 178, 179, 181, 184, 186, 188, 196, 206, 207 Stool, 171, 187, 207 Streptococci, 207 Streptokinase, 14, 46, 97, 115, 207 Stress, 20, 100, 101, 169, 174, 191, 195, 207 Subacute, 186, 207 Subclinical, 186, 207 Subcutaneous, 64, 90, 176, 207 Subspecies, 206, 207 Substrate, 14, 100, 107, 178, 207 Substrate Specificity, 14, 207 Subtrochanteric, 184, 208 Suction, 180, 208 Sudden cardiac death, 5, 208 Sudden death, 7, 208 Sulfates, 4, 208 Sulfur, 82, 179, 181, 190, 208 Sulfuric acid, 208 Supplementation, 9, 208 Surface Plasmon Resonance, 12, 208 Symptomatic, 11, 28, 38, 40, 44, 47, 75, 208 Synapse, 159, 193, 208, 211 Synergistic, 88, 208 Systemic, 18, 90, 106, 111, 118, 119, 120, 162, 163, 166, 178, 183, 186, 187, 202, 208, 213, 214 Systemic disease, 90, 208 Systemic lupus erythematosus, 162, 163, 208 Systolic, 20, 185, 208 Systolic blood pressure, 20, 208 T Tachycardia, 156, 165, 208 Tachypnea, 156, 165, 208 Tamoxifen, 21, 205, 208 Technetium, 50, 208

225

Temporal, 19, 209 Testosterone, 203, 209 Therapeutics, 6, 84, 120, 139, 209 Thigh, 179, 209 Thoracic, 27, 28, 30, 34, 44, 50, 53, 56, 58, 60, 63, 64, 67, 68, 88, 132, 146, 174, 198, 209 Threonine, 191, 196, 201, 205, 209 Threshold, 65, 185, 209 Thrombectomy, 25, 28, 54, 67, 176, 209 Thrombin, 4, 11, 18, 19, 81, 85, 91, 92, 104, 180, 198, 200, 201, 209 Thrombocytes, 198, 209 Thrombocytopenia, 45, 54, 209 Thromboembolism, 7, 10, 11, 23, 35, 73, 76, 83, 98, 101, 106, 110, 134, 135, 136, 143, 144, 145, 209 Thrombolytic, 19, 24, 48, 49, 51, 53, 65, 67, 91, 92, 97, 101, 119, 136, 198, 207, 209 Thrombolytic Therapy, 24, 48, 49, 51, 53, 65, 67, 92, 136, 207, 209 Thrombopenia, 163, 209 Thrombophlebitis, 12, 21, 132, 209 Thrombosed, 199, 209 Thromboses, 163, 209 Thromboxanes, 164, 209 Thyroid, 210, 212 Thyroxine, 160, 197, 210 Tibial Nerve, 94, 205, 210 Tidal Volume, 185, 210 Tissue Plasminogen Activator, 41, 97, 210 Tolerance, 101, 210 Tomography, 13, 14, 15, 16, 17, 24, 26, 32, 34, 37, 39, 44, 46, 49, 53, 54, 56, 59, 65, 76, 114, 172, 189, 204, 210 Tone, 7, 88, 194, 210 Tonus, 210 Tooth Preparation, 159, 210 Topical, 118, 184, 210 Torsion, 186, 210 Toxaemia, 199, 210 Toxic, iv, 10, 172, 182, 210 Toxicity, 6, 95, 175, 210 Toxicology, 7, 128, 210 Toxin, 178, 210 Trachea, 167, 187, 210 Transcription Factors, 9, 211 Transcutaneous, 94, 211 Transfection, 166, 211 Transferases, 182, 211 Translation, 160, 211 Translational, 10, 211

Translocation, 86, 211 Transmitter, 159, 175, 190, 194, 211 Transplantation, 4, 19, 36, 47, 185, 211 Trauma, 35, 43, 70, 77, 90, 105, 106, 111, 143, 169, 211 Tropomyosin, 211 Troponin, 20, 24, 31, 37, 48, 60, 66, 211 Trypsin, 200, 211, 214 Tryptophan, 171, 205, 211 Tumor marker, 165, 211 Tumour, 51, 70, 211 Tunica, 177, 211 Tunica Intima, 177, 211 Tyrosine, 10, 175, 211 U Ulcer, 196, 212 Ulceration, 18, 196, 199, 212 Ultrasonography, 14, 15, 36, 212 Unconscious, 174, 185, 212 Uranium, 209, 212 Urethra, 196, 200, 212 Uric, 107, 108, 212 Urinary, 210, 212 Urinary Plasminogen Activator, 210, 212 Urine, 97, 166, 187, 201, 212 Urokinase, 91, 97, 212 Uterus, 108, 159, 173, 185, 190, 212 V Vaccine, 201, 212 Vagina, 108, 185, 190, 212 Vaginal, 108, 189, 212 Valves, 199, 212, 213 Varicose, 12, 93, 205, 212 Varicose vein, 12, 93, 205, 212 Vasoactive, 88, 107, 212 Vasoconstriction, 7, 19, 178, 212 Vasodilation, 108, 212 Vasodilators, 193, 212 VE, 58, 213 Vena, 65, 80, 98, 213 Vena Cava Filters, 65, 213 Venous blood, 87, 90, 166, 169, 213 Venous Insufficiency, 18, 199, 213 Ventilation, 13, 14, 15, 16, 17, 26, 37, 50, 68, 69, 99, 168, 213 Ventilator, 190, 204, 213 Ventricle, 27, 99, 163, 175, 202, 208, 213 Ventricular, 19, 20, 32, 40, 62, 68, 72, 175, 213 Ventricular Dysfunction, 68, 213 Venules, 166, 167, 177, 213 Vertebrae, 207, 213

Pulmonary embolism

Veterinary Medicine, 127, 213 Virulence, 210, 213 Vitro, 5, 9, 22, 85, 183, 213 Vivo, 5, 9, 10, 85, 95, 213 W Warfarin, 23, 39, 73, 75, 76, 91, 133, 134, 213 White blood cell, 162, 188, 189, 192, 193, 198, 213 Womb, 212, 214 Wound Healing, 19, 22, 100, 169, 190, 214

226

X Xenograft, 162, 214 X-ray, 68, 96, 97, 132, 156, 157, 161, 164, 172, 173, 181, 187, 189, 194, 202, 204, 214 X-ray therapy, 187, 214 Y Yeasts, 181, 197, 214 Z Zygote, 172, 214 Zymogen, 200, 214

227

Pulmonary embolism

228

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