ANTICOAGULANTS 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., 1960Anticoagulants: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-497-00076-8 1. Anticoagulants-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.
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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 anticoagulants. 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 ANTICOAGULANTS ................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Anticoagulants.............................................................................. 6 E-Journals: PubMed Central ....................................................................................................... 25 The National Library of Medicine: PubMed ................................................................................ 28 CHAPTER 2. NUTRITION AND ANTICOAGULANTS ......................................................................... 73 Overview...................................................................................................................................... 73 Finding Nutrition Studies on Anticoagulants ............................................................................ 73 Federal Resources on Nutrition ................................................................................................... 75 Additional Web Resources ........................................................................................................... 75 CHAPTER 3. ALTERNATIVE MEDICINE AND ANTICOAGULANTS ................................................... 79 Overview...................................................................................................................................... 79 The Combined Health Information Database............................................................................... 79 National Center for Complementary and Alternative Medicine.................................................. 80 Additional Web Resources ........................................................................................................... 82 General References ....................................................................................................................... 88 CHAPTER 4. DISSERTATIONS ON ANTICOAGULANTS ..................................................................... 89 Overview...................................................................................................................................... 89 Dissertations on Anticoagulants ................................................................................................. 89 Keeping Current .......................................................................................................................... 90 CHAPTER 5. PATENTS ON ANTICOAGULANTS ................................................................................ 91 Overview...................................................................................................................................... 91 Patents on Anticoagulants........................................................................................................... 91 Patent Applications on Anticoagulants....................................................................................... 96 Keeping Current ........................................................................................................................ 115 CHAPTER 6. BOOKS ON ANTICOAGULANTS ................................................................................. 117 Overview.................................................................................................................................... 117 Book Summaries: Online Booksellers......................................................................................... 117 Chapters on Anticoagulants ...................................................................................................... 118 CHAPTER 7. PERIODICALS AND NEWS ON ANTICOAGULANTS.................................................... 121 Overview.................................................................................................................................... 121 News Services and Press Releases.............................................................................................. 121 Academic Periodicals covering Anticoagulants ......................................................................... 123 CHAPTER 8. RESEARCHING MEDICATIONS .................................................................................. 125 Overview.................................................................................................................................... 125 U.S. Pharmacopeia..................................................................................................................... 125 Commercial Databases ............................................................................................................... 126 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 131 Overview.................................................................................................................................... 131 NIH Guidelines.......................................................................................................................... 131 NIH Databases........................................................................................................................... 133 Other Commercial Databases..................................................................................................... 135 APPENDIX B. PATIENT RESOURCES ............................................................................................... 137 Overview.................................................................................................................................... 137 Patient Guideline Sources.......................................................................................................... 137 Finding Associations.................................................................................................................. 141 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 143 Overview.................................................................................................................................... 143 Preparation................................................................................................................................. 143
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Finding a Local Medical Library................................................................................................ 143 Medical Libraries in the U.S. and Canada ................................................................................. 143 ONLINE GLOSSARIES................................................................................................................ 149 Online Dictionary Directories ................................................................................................... 150 ANTICOAGULANTS DICTIONARY ....................................................................................... 151 INDEX .............................................................................................................................................. 211
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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 anticoagulants 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 anticoagulants, 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 anticoagulants, 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 anticoagulants. 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 anticoagulants, 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 anticoagulants. 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 ANTICOAGULANTS Overview In this chapter, we will show you how to locate peer-reviewed references and studies on anticoagulants.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and anticoagulants, 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 “anticoagulants” (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: •
Myths of Dental Surgery in Patients Receiving Anticoagulant Therapy Source: JADA. Journal of the American Dental Association. 131(1): 77-81. January 2000. Summary: Continuous anticoagulant therapy with warfarin is administered to prevent a variety of medical complications, including thromboembolisms and stroke. When patients receiving continuous anticoagulant therapy are scheduled for dental surgery, a decision must be made whether to continue or interrupt the anticoagulant therapy. This article reports on a study of the related literature in which the author focuses on dental surgery in patients receiving continuous anticoagulant therapy (including those patients whose anticoagulant therapy was withdrawn before they underwent dental procedures). Of more than 950 patients receiving continuous anticoagulant therapy (including many whose anticoagulation levels were well above currently recommended therapeutic levels) who underwent more than 2,400 surgical procedures, only 12 (less
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than 1.3 percent) required more than local measures to control hemorrhage. Only three of these patients (less than 0.31 percent) had anticoagulation levels within or below currently recommended therapeutic levels. Of 526 patients who experienced 575 interruptions of continuous anticoagulant therapy, five (0.95 percent) suffered serious embolic complications; four of these patients died. The author concludes that serious embolic complications, including death, were three times more likely to occur in patients whose anticoagulant therapy was interrupted than were bleeding complications in patients whose anticoagulant therapy was continued (and whose anticoagulation levels were within or below therapeutic levels). Interrupting therapeutic levels of continuous anticoagulation for dental surgery is not based on scientific fact, but seems to be based on its own mythology. Dentists should recommend that therapeutic levels of anticoagulation be continued for patients undergoing dental surgery. Practitioners should consult with the patient's physician if necessary to determine his or her level of anticoagulation before performing dental surgery. 60 references. •
Current Perspectives on Dental Patients Receiving Coumarin Anticoagulant Therapy Source: JADA. Journal of American Dental Association. 128(3): 327-335. March 1997. Summary: Despite approximately 40 years of experience with oral anticoagulant drugs, controversy still exists about the safety of dental treatment in patients receiving this therapy. This article reviews this topic in depth and offers detailed recommendations for the dental management of patients receiving coumarin anticoagulant therapy. The authors review how coumarin affects coagulation, present the newly accepted international normalized ratio (INR) for monitoring anticoagulation status, and describe current medical practice with respect to the use of coumarin. The authors conclude that while a risk-benefit assessment must be made for each patient, dentists can perform most dental treatments safely in patients undergoing coumarin therapy without the need for hospitalization or cessation of anticoagulant therapy. 2 figures. 3 tables. 60 references. (AA-M).
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Stop the Nonsense Not the Anticoagulants: A Matter of Life and Death Source: New York State Dental Journal (NYSDJ). 68(9): 24-26. November 2002. Contact: Available from Dental Society of the State of New York. 7 Elk Street, Albany, NY 12207. (518) 465-0044. Summary: Many dental patients have medical problems that require the administration of oral anticoagulants to prevent catastrophic or life-threatening thromboembolic events. Examples include patients with medical conditions such as atrial fibrillation, mechanical heart valves, recent pulmonary embolism, stroke, deep vein thrombosis, anticardiolipin syndrome, and coronary artery disease. The oral anticoagulant used most commonly in these instances is Coumadin. This article presents an evidence-based approach to the treatment of patients on anticoagulants. The authors note that stopping the administration of Coumadin to perform routine dental procedures can be life threatening. Many physicians and dentists believe these patients may not have routine dental procedures, including cleanings and uncomplicated extractions, while on Coumadin for fear of serious postoperative bleeding. The authors conclude that no scientific evidence exists to support removing these patients from Coumadin to perform routine dental procedures and uncomplicated extractions, provided the patient's level of anticoagulation is within therapeutic range. 1 table. 7 references.
Studies
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Warfarin Sodium (Coumadin) Anticoagulant Therapy for Vascular Access Patency Source: ANNA Journal. American Nephrology Nurses' Association Journal. 25(2): 195204. April 1998. Contact: Available from American Nephrology Nurses' Association. Box 56, East Holly Avenue, Pitman, NJ 08071. (609) 256-2320. Summary: The increase of patients who are older or have diabetes brings about a corresponding increase in the use of synthetic vascular access grafts, placed for hemodialysis access. Synthetic grafts are often chosen for patients with poor vasculature because compromised blood vessels cannot support native arteriovenous fistulas. This article discusses the use of warfarin sodium (Coumadin), a drug used as anticoagulant therapy to help maintain vascular access patency. Warfarin sodium is often chosen because of its predictability and bioavailability to interrupt the coagulation cascade to prevent thrombus formation. The author discusses the actions, interactions, monitoring, and adverse effects of this drug. The main complication of warfarin sodium is bleeding, or hemorrhage, that can occur in any tissue or organ. The risk for bleeding increases in the presence of certain conditions, including older age, history of gastrointestinal bleeding, renal insufficiency, or anemia. The author stresses that once nephrology nurses have an understanding of warfarin sodium and the methods of monitoring, it is important for them to provide education for patients about the drug. The author concludes that, although it has not been truly determined if warfarin sodium use will help prolong access patency, the use of the drug will most likely be continued to prevent thrombosis because of its mechanism of action to interrupt coagulation. The article includes extensive charts listing medications with which warfarin sodium may interact, indications, and contraindications. The article is worth 2.5 contact hours of continuing education credit from the American Nephrology Nurses Association (ANNA); the posttest is included at the end of the article. 1 figure. 5 tables. 21 references. (AA-M).
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Dental Management of Patients on Anticoagulant Therapy Source: General Dentistry. 43(4): 351-354. July-August 1995. Summary: This case report highlights changes in the dental management of patients on anticoagulant therapy. A 37 year old man was examined for restorative treatment in the dental office. Diagnosed with Marfan's sign, the man had an aortic prosthesis and was taking warfarin sodium (Coumadin), atenolol (Tenormin), and nitroglycerin. He was premedicated for the dental work according to the American Heart Association (AHA) guidelines for subacute bacterial endocarditis prophylaxis. He had bilateral mandibular amalgam restorations, for which he received bilateral mandibular block injections. A few days after treatment, the patient awoke with pain in his right mandible and swelling in the right internal pterygoid muscle and infratemporal fossa. He was eventually diagnosed with a hematoma of the pterygoid muscle. After the diagnosis was made and the anticoagulant medications were regulated, the patient was discharged. The hematoma gradually was absorbed and function returned over a period of weeks. The authors conclude that this case demonstrates that individuals on long-term anticoagulant therapy are at risk of bleeding and hematoma formation from injection of local anesthesia and routine dental care. To assist dentists in managing patients on longterm anticoagulant therapy, a patient care management algorithm is provided. 6 figures. 5 references. (AA-M).
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Dental Treatment for Patients on Continuous Anticoagulant and Antiplatelet Drugs: Questions and Answers Source: Dentistry Today. 20(8): 74-75. August 2001. Contact: Available from Dentistry Today Inc. 26 Park Street, Montclair, NJ 07042. (973) 783-3935. Summary: This continuing education article helps dentists feel comfortable providing care to patients on continuous anticoagulant and antiplatelet drugs. Patients may be on these drugs as a result of a variety of underlying conditions, including artificial heart valve, atrial fibrillation, valvular heart disease, history of deep vein thrombosis (clotting) or pulmonary embolism (blockage in a lung blood vessel), history of systemic embolism, left ventricular dysfunction or thrombus, and history of transient ischemic attack or stroke. Continuous anticoagulant and antiplatelet drugs are used to prevent a variety of medical complications, including thromboembolism and stroke. These medications may also cause hemorrhage after trauma, including after dental surgery. In this article, the author answers common questions about delivering dental treatment to these patients. Topics include the drugs coumadin and heparin and how they are used, the risks of continuing anticoagulation therapy versus withdrawing anticoagulation for surgical dental procedures, when physician consultation should be utilized, the role of aspirin, a newer antiplatelet drug clopidogrel (Plavix), and how to control bleeding in patients taking anticoagulants or antiplatelet drugs. Appended to the article is a posttest with which readers can obtain continuing education credits. 12 references.
Federally Funded Research on Anticoagulants The U.S. Government supports a variety of research studies relating to anticoagulants. 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 anticoagulants. 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 anticoagulants. The following is typical of the type of information found when searching the CRISP database for anticoagulants: •
Project Title: A NOVEL FAMILY OF ANTICOAGULANTS FROM IXODES SCAPULARIS Principal Investigator & Institution: Ledizet, Michel E.; L2 Diagnostics, Llc Box 8175 New Haven, Ct 94904 Timing: Fiscal Year 2003; Project Start 22-AUG-2003; Project End 31-AUG-2004
2 Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).
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Summary: (provided by applicant): The overall objective of this proposal is to evaluate the anticoagulant properties of a family of novel tick salivary proteins Ixodes scapularis, the black-legged tick, circumvents host hemostatic mechanisms as it engorges on vertebrate hosts. This tick's saliva contains potent anticoagulants, including a Factor Xa inhibitor. Purified salivary proteins with anticoagulant activity were subjected to Nterminal sequencing. A corresponding tick salivary cDNA was cloned that encoded a 96 kDa protein, designated Salp9A. This protein is homologous to Salp14, which we previously identified by immunoscreening a tick salivary gland cDNA expression library. Additional protein and cDNA sequencing indicate that I scapularis salivary glands express at least ten different Salp14-related proteins. We expressed and purified recombinant Salp14, and found that it inhibits coagulation and Factor Xa. These data suggest that we have discovered a new family of anticoagulants. In Phase I experiments we will obtain full-length cDNAs encoding selected Salp14 family members. Recombinant proteins will be expressed from these cDNAs. The recombinant proteins will be compared to partially purified salivary anticoagulants in anticoagulant and protease inhibition assays. These studies will relate structure and function, and provide a rational basis for selecting anticoagulant molecules for Phase II animal studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: A SCAFFOLD FOR CARDIOVASCULAR TISSUE ENGINEERING Principal Investigator & Institution: Ameer, Guillermo A.; Biomedical Engineering; Northwestern University 633 Clark Street Evanston, Il 60208 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-JUL-2005 Summary: (provided by applicant): Tissue engineering offers the potential to provide biological substitutes to restore, maintain, or improve tissue function. The construction of tissue engineered heart valves or blood vessels could potentially offer several advantages over currently used therapeutic interventions or devices. Advantages include the limitation or avoidance of anticoagulants, the potential for tissue growth with the patient, and the use of autologous tissues that can repair and remodel using the body's natural mechanisms. Therefore, an important area of research is the development of suitable scaffolds that meet the demands of cardiovascular applications. To engineer cardiovascular tissues, there is a need to develop scaffolds that can closely model the mechanical properties (elasticity) of the native tissue (valve leaflets, blood vessels) and are amenable to implantation. It is hypothesized that polymers based on copolymers of sebacic acid and glycerol (PGSA) could potentially serve as suitable elastomeric scaffolds for cardiovascular applications. It is also hypothesized that a novel optical technique referred to as light scattering spectroscopy can be used to non-invasively monitor the tissue formation and remodeling processes of cells on the scaffold. Sebacic acid and glycerol are non-toxic with the latter offering the potential for cross-links and hydrogen bonding, properties that could potentially confer elasticity to a material. The goal of the research is to evaluate the feasibility of using PGSA as scaffolds to engineer cardiovascular tissues such as heart valves and blood vessels. Towards this goal, the specific aims are to: 1) Synthesize and characterize a biodegradable elastomeric scaffold for potential use in cardiovascular tissue engineering. 2) Investigate whether LSS can asses the micro-architecture/development of intact and cell-seeded elastomeric scaffolds, and 3) Test the biocompatibility and degradation of the elastomeric scaffold in vitro as well as in vivo. The biodegradable elastic polymer developed from this research could potentially provide an inexpensive scaffold for cardiovascular tissue engineering and for other devices such as stents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ACTION OF FUCOIDAN DURING THE ACTIVATION OF PLASMINOGEN Principal Investigator & Institution: Doctor, Vasant M.; Prairie View Agri & Mech University Box 519 Prairie View, Tx 77445 Timing: Fiscal Year 2002 Summary: Considerable attention has been focused recently on the therapeutic value of tissue plasminogen activator (t-PA) as a thrombolytic agent for the treatment of heart attacks and strokes. One possible problem with this therapy is the rapid reocclussion of the affected artery. Therefore, patients treated with t-PA are treated concomitantly with heparin. However, heparin cannot prevent coronary reocclussion effectively, since it promotes binding of thrombin to fibrin polymer by forming a ternary complex, thus lowering the inactivation of thrombin by anti-thrombin III. On the other hand, fucoidan [sulfated poly (L-fucopyranose)] from marine algae Fucus Vesiculosis, is reported to show in vitro and in vivo anticoagulant activity mediated by heparin co-factor II, which will inactivate thrombin, even on a fibrin surface. The enzyme response for lysis mediated by heparin co-factor II, which will inactivate thrombin, even on a fibrin surface. The enzyme responsible for lysis of fibrin is plasmin (Plm), which is generated from the inactive plasma precursor plasminogen (plg) by the action of specific activators. Our laboratory has reported that fucoidan enhanced the in vitro activation of Plg to Plm by t- pA or by urokinase (u-PA). This proposal is concerned with the mechanism of this enhancement and will consist of the following investigations. 1) Purification of fucoidan by DEAE or ECTEOLA cellulose, or QAE sepharose chromatography followed by degradation, using fucosidase or hydrochloric acid and isolation of the degradation products by gel filtration or ultra-filtration procedures. 2) The purified fucoidan or the degradation products will be characterized according to the molecular weight by using size exclusion chromatography, and 1H- nmr OR 13 C-NMR spectroscopy will be used to determine the location of the sulfate groups and the nature of the glycosidic bonds. 3) Fucoidan, which exhibits the optimum enhance of Plm generation, will be used for studying its interactions in the various in vitro systems during the activation enhancement of Plm generation, will be used for studying its interactions in the various in vitro systems during the activation of Glu- POLG or LysPlg, by t-PA or uPA, or during inhibition of the activation by plasminogen activator inhibitor (PAI-1). 4) The binding site of fucoidan, with Glu-Plg, t-PA, uPA, or PAI-1 will be investigated by affinity chromatography, using fucoidan-sepharose. 5) Conformation changes of Glu-Plg or Lys-Plg induced during the activation of Plg in the presence of fucoidan or 6-amino hexanoic acid (6-AHA), alone or in combination, will be examined by using circular dichroism spectroscopy. In each of the above studies the results of the fucoidan will be compared with sulfated glycosaminoglycans occurring in human tissues or heparinoids. The proposed study will give an insight into the mechanisms by which these compounds modify the normal processes and may eventually resulted in the development of a new generation of anticoagulants that may replace heparin as adjunct therapy with t-PA. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ANTICOAGULANTS ON DEVELOPMENT OF OSTEOPOROSIS DURING PREGNANCY Principal Investigator & Institution: Kiwi, Robert; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2002
Studies
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Summary: The specific aim of this study is to assess the effect of heparin therapy during pregnancy on bone density. The study is prospective and observational. Potential subjects include women receiving heparin therapy prophylactically for a history of thromboembolism and patients receving therapy for deep vein thrombosis, thrombophlebitis or any condition requiring heparin. Blood and urine samples and a dietary intake history are taken at 20 weeks gestation, 6 weeks postpartum, and 6 and 12 months postpartum. Bone density is measured at 20 wks gestation, following delivery and 6 and 12 months postpartum. The spine is measured after delivery. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
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 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: CYP2C9--ACTIVE SITE STRUCTURE--MOLECULAR MODELING ASPECTS Principal Investigator & Institution: Trager, William F.; Professor; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002 Summary: The long-term aim of the research described in this proposal is to understand the structural basis underlying the unique substrate specificities of the human CYP2C
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proteins. This is important for the avoidance of inhibitory drug-drug interactions involving this important P450 sub-family, and in particular CYP2C9, during the development of new therapeutic agents. Our preliminary data derived from CoMFA modeling, homology modeling and site-directed mutagenesis studies, suggest that the binding of coumarin anticoagulants and anticonvulsant hydantoins to CYP2C9 is governed by an aromatic binding interaction within the B'-helix, and two electrostatic interactions (E1 and E2) within elements of the F, G and I-helices of the enzyme. The primary goal of this research is to test this hypothesis in order to refine our active-site model for CYP2C9. CYP2C19, which share greater than 90% sequence homology with CYP2C9, also metabolizes the coumarins and hydantoins but generates metabolite profiles quite distinct from CYP2C9. Therefore, the active-sites of CYP2C9 and CYP2C19 likely share some common binding determinants which should facilitate the related goal of developing a three-dimensional active-site model for CYP2C19. The Specific Aims of this proposal are; 1. Construction of new CoMFA models for CYP2C9 and CYP2C19 based on Ki values for the inhibition of both isoforms by Type I and Type II ligands. 2. Identification of active-sites residues in CYP2C9 and CYP2C19 through photo-affinity labeling and analysis of adducted residues by electrospray and MALDI mass spectrometry. 3. Identification of electrophilic binding site determinants in CYP2C9 through the construction of hybrid CYP2C9/CYP2C19 proteins and point mutants, and analysis of their interaction with valproic acid, phenytoin and phenprocoumon. This three-tiered approach involves the use of complementary techniques which will permit the iterative refinement of three-dimensional structural representations of CYP2C9 and CYP2C19. This approach provides a powerful internal control for the procedures which we are using, by ensuring that discrete CYP2C9 and CYP2C19 structural representations are created rather than a low resolution "global" CYP2C model. Finally, if we can develop discrete models for the closely related CYP2C9 and CYP2C19 isoforms, there should be little impediment to the future generation of active-site models for the other human CYP2C isoforms. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DESIGNING MECHANISM-BASED ANTICOAGULANTS Principal Investigator & Institution: Desai, Umesh R.; Assistant Professor; Medicinal Chemistry; Virginia Commonwealth University Richmond, Va 232980568 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2007 Summary: (provided by applicant): Thrombotic and vascular disorders are among the leading cause of deaths in the US annually. Unfractionated heparin and low-molecularweight heparins have become major anticoagulant drugs for use in these hematological disorders with combined annual sales of more than $ 3 billion. Unfortunately heparin and low molecular weight-based anticoagulation therapy is beset with several problems including bleeding complications. Heparin anticoagulation therapy is primarily based on the ability to accelerate the inhibition of factor Xa and thrombin by antithrombin, a plasma serine proteinase inhibitor. At the molecular level, heparin binding induces a conformational change in antithrombin ('activation') to greatly enhance its ability to inhibit factor Xa. However, the polyanionic nature of heparin also results in non-specific interactions leading to the numerous undesirable side effects. Alternative approaches based on rationally designed small non-sugar heparin-mimics that eliminate these side effects and possibly possess advantages, such as oral activity, are therefore highly desirable. Our central hypothesis is that efficient activation of antithrombin leading to specific inhibition of factor Xa can be achieved with small non-sugar molecules. We propose to synthesize and study rationally designed small organic molecules as
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conformational activators of antithrombin. Towards this end we will I) synthesize and characterize rationally designed bicyclic-unicyclic, bicyclic-linker-unicyclic and bicyclicbicyclic activators of antithrombin, II) investigate the molecular interaction of antithrombin with designed, small heparin mimetics using biochemical and biophysical techniques, and III) design rational advanced organic, non-sugar activators based on initial promising leads. Detailed investigation of the rationally designed molecules will provide the knowledge to deduce quantitative structure-function relationship critical for the design of an effective non-sugar heparin-mimic. These aims will be investigated utilizing computerized molecular modeling; fluorescence spectroscopic study of interactions; rapid kinetic determination mechanism of interaction; enzyme kinetics; and synthetic organic chemistry. This fundamental research will establish the principles of effective conformational activation of antithrombin by small nonheparin molecules for accelerated inhibition of factor Xa. Successful completion of this research will contribute fundamental knowledge for the design of an effective anticoagulant I) with reduced non-specific adverse effects normally associated with heparin therapy and II) with better oral activity. 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
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Anticoagulants
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 •
Project Title: ECLS IN MULTIPLE ORGAN FAILURE Principal Investigator & Institution: Bartlett, Robert H.; Professor of Surgery; Surgery; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 01-AUG-1980; Project End 30-JUN-2004 Summary: Over the last 25 years our laboratory research on extracorporeal gas exchange and perfusion (ECMO) has progressed from oxygenator design, through the physiologic response to ECMO, through the development of extracorporeal technology to safe, simple automated systems which can be used to support cardiac or pulmonary function for days. Clinical success with ECMO indicates that expansion to total mechanical extracorporeal life support (ECLS) is feasible, but expansion of the technology requires a solution to two problems: 1) anticoagulation and thrombocytopenia, and 2) multiple organ failure. Despite many innovative approaches to anticoagulation and new prosthetic surfaces, systemic heparin anticoagulation is still required for extracorporeal circulation. A new group of anticoagulants inhibit clotting at specific early stages of the cascade. We will evaluate inhibitors of Factor IXa and Xa, used systemically or on the surface. Nitric oxide, a potent inhibitor of platelet adherence and activation, can be incorporated into the plastic materials and ventilating gas in the ECMO system, eliminating surface thrombogenesis, platelet consumption, and systemic anticoagulation without affecting endogenous platelet function. This research will develop and characterize thrombosis prevention leading to prolonged extracorporeal circulation without anticoagulation or thrombocytopenia. This will allow extension of mechanical life support from weeks to months, and initiate new approaches to ECLS. The nonthrombogenic surface combined with high blood flow and a unique albumin-based hemodiafiltration system can extend mechanical life support to liver failure and sepsis. The significance of this research is to decrease the mortality from cardiorespiratory and multiple organ failure. By studying prolonged support in experimental animals we will improve our understanding of the mechanisms and treatment of multiple organ failure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: EPIDEMIOLOGY FIBRILLATION
OF
ANTICOAGULATION
IN
ATRIAL
Principal Investigator & Institution: Singer, Daniel E.; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 30-SEP-1997; Project End 31-MAR-2006
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Summary: We propose to continue our studies of a uniquely informative cohort of greater than 13,559 patients with atrial fibrillation (AF) from Kaiser Medical Care Program of Northern California ("Kaiser"). Our overall goal remains to optimize prevention of stroke in AF by improving selection of patients treated with anticoagulants, and by improving the management of anticoagulation. AF is the most common significant cardiac rhythm disorder. Its frequency increases strikingly with age, reaching a prevalence of nearly 10 percent in those over age 80. AF is also a powerful risk factor for stroke, raising this risk 5-fold. Randomized trials (RCTs) have established that anticoagulation largely removes the stroke risk posed by AF. Nonetheless, warfarin remains a burdensome and risky therapy. There is considerable uncertainty whether warfarin therapy will prove beneficial under real-world conditions. Guidelines call for long-term anticoagulation, and for use of anticoagulants in the elderly. Yet, the RCTs were relatively brief, with a mean follow-up of only 18 months, and few patients greater than or equal to 80 years old were studied. During the 2.7 years of current funding we have established methods to assemble a very large AF cohort, characterize baseline features and warfarin status, and follow for thromboembolic and hemorrhagic events. This has been accomplished efficiently via comprehensive automated clinical and administrative Kaiser databases supplemented by medical chart review. Continued follow-up of our AF cohort will provide unique assessments of both the long-term impact of anticoagulation and the impact of anticoagulation among the oldest patients with AF. Further, we will be able to address other important controversies including the need for anticoagulation in patients greater than or equal to 65 years old without other risk factors for stroke, and the optimal intensity of anticoagulation in older AF patients. In addition, we will address the provocative new finding that estrogen replacement therapy substantially raises the risk of stroke among women with AF. In all, continued study of our cohort will efficiently provide powerful insights into optimizing stroke prevention strategies for the many older Americans with AF. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FACTOR VA INTERACTIONS REGULATING PROTHROMBIN ACTIVATION Principal Investigator & Institution: Bock, Paul E.; Associate Professor; Physiology and Biophysics; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2003; Project Start 01-APR-1994; Project End 31-MAR-2007 Summary: (provided by applicant): The ultimate goal of the proposed studies is to define the molecular mechanisms of factor V function in normal hemostasis and in the pathology of thrombosis. The studies address major gaps in understanding the function of proteinase exosites in substrate recognition mechanisms of the procoagulant activation of human factor V, factor Va cofactor activity in prothrombin (Pro) activation, and the anticoagulant inactivation of factor Va by activated protein C (APC). The factor V activation pathway is hypothesized to involve thrombin exosites I and II in substrate recognition of factor V activation species, which control the pathway direction and the expression of specific binding sites for factor Xa and Pro. Factor Va-directed substrate recognition of Pro activation species is hypothesized to occur through exosites expressed on factor Xa within the factor Xa-Va catalytic complex, and between proexosite I on Pro and the factor Va heavy subunit. Binding is coupled to engagement of the factor Xa catalytic site in a conformational change required for proteolytic cleavage. The Pro activation pathway is controlled in part by selective expression of increased (pro) exosite I binding affinity for factor Va on the activation intermediates, modulated by fragments 2 and 1.2, and phospholipid membranes. The mechanism of
14
Anticoagulants
factor Va inactivation by APC and the cofactor activity of protein S are hypothesized to result from exosite-mediated assembly on membranes of APC-factor Va-protein S and competing factor Xa-Va complexes. The mechanisms will be evaluated in quantitative fluorescence equilibrium binding studies, steady-state and rapid-reaction kinetic studies. Fluorescent Pro derivatives specifically labeled in the zymogen catalytic site have been developed as new probes of the mechanisms. Specific aims are: (1) To delineate the kinetic mechanism of factor V activation, the expression of binding sites for factor Xa and Pro species, and the roles of thrombin exosites in factor V substrate recognition and pathway direction; (2) To determine the specificity of the binding site on factor Va for Pro activation species, and its role in the individual molecular events in substrate recognition by the factor Xa-Va complex; (3) To define the contribution of proexosite I-mediated Pro-factor Va interactions to the mechanism of regulation of the Pro activation pathway, including substrate channeling; (4) To elucidate assembly of membrane-bound factor Xa-Va and APC-factor Va-protein S complexes in regulation of factor Va inactivation. The results of the studies will contribute to the mechanistic information needed for design of new anticoagulants that act at the level of the exositedirected regulation of procoagulant and anticoagulant systems. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETIC VARIATION IN FACTOR IX AND THROMBOSIS RISK Principal Investigator & Institution: Howard, Tom E.; Medicine; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2003; Project Start 15-AUG-2003; Project End 31-JUL-2007 Summary: (provided by applicant): Plasma factor IX (f-IX) levels influence thrombosis risk. Recent discoveries from the Genetics Analysis of Idiopathic Thrombophilia (GAIT) Project demonstrate that: 1) the population variation in thrombosis risk has a high heritability (h2), equal to or > 60%, largely due to unknown genetic factors; 2) a substantial portion of these heritable factors influence thrombosis risk by modulating intermediate hemostasis traits like f-IX; 3) the variation in f-IX levels also involves a substantial genetic component (h2 about 40%) that is entirely unknown; and 4) the variation in thrombosis risk and f-IX levels are strongly correlated genetically (rho[sub g] about 60%), indicating a number of the f-IX quantitative trait loci (QTLs) also influence thrombosis risk. These findings strengthen our proposal because a number of these QTLs are likely to reside in the f-IX locus itself as the expression of this protein is largely regulated at transcriptional and post-transcriptional levels through molecular events involving elements in essential gene regions. Indeed, two f-IX cis-elements, one in the promoter (AE-5') and one in the 3'-UTR (AE-3'), are responsible for the increase in f-IX levels with age. This implies that some of the population variation in f-IX levels may be age-related. Since we found that both age-elements are polymorphic, G-793A in AE-5' and a dinucleotide repeat (DNR) in AE-3', these variations are candidate QTL for f-IX levels and thrombosis risk. Our hypothesis that these variations, along with a f-IX coding region polymorphism (A23387G), modulate f-IX levels and/or catalytic activity, and therefore influence thrombosis risk leads to these Aims: Aim 1: To determine if a single nucleotide (SNP), G-793A, located within an essential f-IX promoter element influences f-IX levels and thrombosis susceptibility. Aim 2: Determine if a polymorphic DNR, which is located in a regulatory element in the 3' -untranslated region (3' -UTR), influences f-IX mRNA stability, plasma f-IX levels and thrombosis risk. Aim 3: Determine if A23387G, a f-IX coding SNP non-conservatively substituting an alanine (Ala) residue for a conserved threonine (thr), influences the rate of f-IX activation, plasma f-IX levels and thrombosis risk. Our long-range goal is to provide more accurate
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diagnostic approaches, including pre-clinical pedisposition testing, by improving our understanding of the inherited liability to thrombosis, and ultimately to supply the foundation for identifying the interacting factors influencing hemostasis as potential therapeutic targets for more efficacious and safer anticoagulants and antithrombotic agents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GLYCOSYLPHOSPHATIDYLINOSITOL ANTITHROMBIN
(GPI)
ANCHORED
Principal Investigator & Institution: Whinna, Herbert C.; Pathology and Lab Medicine; University of North Carolina Chapel Hill Aob 104 Airport Drive Cb#1350 Chapel Hill, Nc 27599 Timing: Fiscal Year 2002; Project Start 15-AUG-1999; Project End 31-JUL-2004 Summary: Thrombosis is a major cause of morbidity and mortality in the United States. Most patients with thrombotic disorders require long-term therapy with oral anticoagulants, which have numerous side effects and present clinical challenges in situations of surgery or other medical interventions. Targeting a drug to the vascular endothelium, which is a primary site of action for hemostatic proteins, could avoid these systemic side effects. The overall goal of this project is to create a new antithrombotic molecule that we have termed "glycosylphosphatidylinositol(GPI)- anchored antithrombin" (AT-GPI). When expressed in cells, this antithrombotic protein should be tethered from the cell surface, concentrating it at the primary site of thrombotic activity. We propose to: i) Generate AT-GPI cDNA using standard molecular biology techniques; ii) Establish in vitro endothelial cell lines that express AT-GPI and assay this system for the antithrombotic activity of AT-GPI; iii) Use gene therapy technology to establish ATGPI in an in vivo animal model and test for antithrombotic activity'; iv) Engineer the tissue factor promoter upstream of the AT-GPI cDNA and determine whether it can regulate AT-GPI expression in response to inflammatory signals. This project will provide the Principal Investigator with new training using the techniques of molecular biology, cell culture, adenoviral gene therapy and animal models to complement his earlier training in protein biochemistry. This training will increase the number of tools and techniques available to the Principal Investigator in his future study of the normal and pathologic biology of the vascular system and thereby greatly enhance his chances of success in pursuing a career in academic medicine. In addition, gene therapy using these types of proteins could be a powerful new approach in the treatment of thrombotic disorders and in the prevention of thrombus formation on highly susceptible tissues, such as atherosclerotic arteries and venous grafts. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IMPROVING PATIENT SAFETY BY REDUCING MEDICATION ERRORS Principal Investigator & Institution: Strom, Brian L.; Professor of Medicine and Pharmacology; Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 07-SEP-2001; Project End 31-AUG-2006 Summary: (PROVIDED BY APPLICANT) Medication errors are among the most common and potentially preventable types of medical errors, accounting for more deaths than motor vehicle accidents, breast cancer, or HIV, and an annual cost of $17 to 29 billion. The elderly are particularly at risk for such complications. The highest risk
16
Anticoagulants
drugs include anticoagulants, anticonvulsants, antimicrobials, and digoxin. The most frequent serious adverse outcomes include bleeding and acute renal failure. Medication errors can occur anywhere in the medication use process, including diagnosis, prescribing, dispensing, administering, ingesting, and monitoring. Sources of medication errors are quite varied. Among health care professionals, factors such as work stress, distractions, interruptions, inadequate training, fragmented information, or information overload may increase the risk of committing errors, such as prescribing the wrong drug or dose, or omitting needed action in the course of delivery of care, such as failing to properly monitor the use of nephrotoxic drugs or anticoagulants. Among patients, factors such as advanced age, frailty, cultural or literacy barriers, mental illness or incapacity, or lack of adequate social support may contribute to poor adherence with a specified therapeutic regimen. Poor adherence accounts for almost a quarter of all hospital admissions attributed to drugs, and can take the form of overuse, underuse, or erratic use of the drug. Building on its 20 years of experience studying adverse drug reactions and other medication safety problems, the University of Pennsylvania proposes a Center of Excellence for Patient Safety Research and Practice. The proposed Center will re-focus this large past experience on the expansion of this patient safety knowledge base through multidisciplinary research and education programs that are designed to identify and implement systems approaches to reducing error in the use of medications. In particular, we propose a program that will combine investigators in pharmacoepidemiology, health services research, biostatistics, occupational medicine, sociology, psychology, and economics to address a theme of "Improving Patient Safety Through Reduction of Errors in the Medication Use Process." The program will be composed of four projects and four cores, based at the University of Pennsylvania and linked to the government of the State of Pennsylvania and to the network of Centers for Education and Research in Therapeutics. Each of the four cores will serve the four projects, in such a way as to maximize quality and efficiency simultaneously. Project 1 will study patient and system factors that are predictive of hospitalizations due to doserelated medication errors among elderly individuals taking specific high-risk drugs (warfarin, phenytoin, and digoxin), using a State-run population-based pharmaceutical benefit program. Project 2 will study human and medical practice factors as predictors of poor adherence to warfarin therapy in an anticoagulation clinic setting created as a systems approach to prevent medication errors. Project 3 will study medication errors as causes of preventable acute renal failure in the inpatient setting, despite the existence of a pharmacokinetic monitoring service created to prevent such problems. Project 4 will study conditions that lead to medication errors among physicians, with emphasis on work conditions that increase stress, such as workload, schedules, work organization, shifts, and patient/staff ratios. Core A will be an administrative core, responsible for coordination. Core B will be a data collection core, responsible for all field activities. Core C will be a biostatistics and data management core, responsible for data entry, management, and analysis. Core D will be a dissemination core, responsible for an extensive dissemination program, as the results of the program emerge. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: LUPUS ANTICOAGULANTS AND THE PROTEIN C PATHWAY Principal Investigator & Institution: Esmon, Naomi L.; University of Oklahoma Hlth Sciences Ctr Health Sciences Center Oklahoma City, Ok 73126 Timing: Fiscal Year 2002 Summary: We have found that the membrane requirements of the APC anti- coagulant complex differ markedly from those of the pro-coagulant complexes, These
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requirements mimic those of at least a population of autoantibodies found in thrombotic patients, providing both specificity and a link between the APC pathway, lupus anticoagulant/anti- phospholipid antibodies and thrombosis. More recently, we have observed that phospholipid oxidation further enhances APC activity selectively. Oxidation is considered a central feature of many inflammatory diseases including lupus and cardiovascular disease. It is the goal of this application to determine the relationship between the different membrane structural requirements of the prothrombinase and APC complexes with an emphasis on the role of oxidation in these reaction. We will determine whether currently unknown plasma factors are involved in the oxidation, what the active products are and whether any modification to the proteins of the APC complex occur as a result of this oxidation. The lipophilic antioxidant, alpha-tocopherol is regarded as protective against oxidative damage in various diseases, including heart disease. We will determine whether incorporation of tocopherol derivatives in membranes differentially affects the pro- and anti- coagulant reactions which may have direct protective effects against thrombus formation. Patients have been identified whose immunoglobulin inhibits only the oxidation dependent anticoagulant APC activity, while others inhibit the oxidation dependent and independent activity equivalently. It is not known whether these represent different risk groups. Immunoglobulin from thrombotic patients recruited during the first grant period will be screened for the prevalence of anti- APC activity and the binding specificities determined. A chimeric form of protein C whose membrane requirements more closely resemble those of the pro-coagulant complexes will also be used in these studies. We will attempt to correlate APC inhibition and binding patterns with the risk of rethrombosis in the study population to determine whether such classification is useful in the identification of pro-thrombotic antibodies for the diagnosis and/or treatment of thrombosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: OPTIMIZING THERAPEUTIC RATIOS FOR HERBS Principal Investigator & Institution: Goldman, Peter; Maxwell Finland Professor; Medicine; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 01-SEP-2000; Project End 30-JUN-2005 Summary: Herbal remedies are used by an estimated 12% of the adult population in the United States. Ginkbo biloba is one of the most widely used herbs, with sales last year of more than $90 million. Ginkbo has traditionally been thought to improve circulation, particularly to the brain, and it has been used both to increase cognition and to improve peripheral circulation. Recent clinical trial indicating improve cognition in patients with early stage Alzheimer's Disease should increase ginkgo's use among older adults. Use, however, may not be without risk. The medical literature contains several case reports of an association between ginkgo use and severe risk. The medical literature contains several case reports of an association between ginkgo use and severe hemorrhage, and studies in both human subjects and animals confirm that certain fractions of ginkgo impair normal coagulation. Clinical reports suggest an interaction between ginkgo and such prescribed anticoagulants as aspirin and warfarin, while animal studies show3 an interaction with the anti- thrombotic drug ticlopidine. In the case of aspirin the interaction may result from combining direct effects on platelet aggregation, but with the other drugs an interaction at the level of cytochrome P450 system is likely. The goal of this proposal is to investigate is to investigate whether ginkgo may interact with such prescribed anticoagulants as warfarin and ticlopidine at the level of the cytochrome
18
Anticoagulants
P450 system. Additional studies will determine which fractions of ginkgo are responsible for it anti- platelet effects and how these fractions relate to ginkgo's nonspecific antioxidant effects, which may believe are responsible for ginkgo's benefit. Such fractions will also be assayed for their capacity to prevent apoptosis induced in embryonic rat nerve cells by oxidative stress. The project will also address the issue of the consistency of herbal products, which our preliminary studies suggest varies from product to product as well as from to batch of the same product. By addressing the issues of herbal product consistency and using laboratory models to define chemical and biological mechanisms of potential clinical significance, this proposal offers a paradigm for the multi-disciplinary study of commonly used herbal products. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PREVENTING HARM FROM ALCOHOL USE IN OLDER ADULTS Principal Investigator & Institution: Moore, Alison A.; Medicine; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2003; Project Start 15-AUG-2003; Project End 31-JUL-2007 Summary: (provided by applicant): Up to 40 percent of older persons who drink may be at-risk for harm. This risk is due to age-related physiological changes that increase the effects of a given dose of alcohol and age-associated increases in comorbidity and medication use that may cause adverse effects when even small amounts of alcohol are consumed. Most trials of brief advice to reduce drinking among primarily younger populations have reduced subjects' alcohol use by 10-20 percent. These trials have focused on drinkers who are at risk because of the amount they drink, or because they have symptoms of alcohol abuse or dependence. No trials have yet focused on older drinkers who are at risk because of the interaction of alcohol use and co-morbidity (e.g., diabetes, hypertension) and medication use (e.g., anticoagulants, nonprescription antihistamines). To test whether a screening and brief advice preventive intervention targeted to older persons may reduce such at-risk drinking and prevent subsequent harm, we propose a 12-month, randomized, controlled trial involving 880 subjects attending primary care clinics at two non-academic sites. Our intervention will consist of advice given to both at-risk drinkers and their physicians personalized to address the particular reasons a subject is identified as an at-risk drinker. We will identify at-risk drinkers using a new screening measure, the Short Alcohol-Related Problems Survey (shARPS). Respondents may be identified as at-risk drinkers because they have a single risk (e.g., drinking and using benzodiazepines) or multiple risks (e.g., drinking and using narcotics, drinking and having depression). At-risk drinkers will be randomized to either receive brief advice about at-risk drinking (intervention) or a booklet on healthy behaviors (control). To assess the efficacy of the intervention, subjects will undergo assessments of their alcohol-associated risks at recruitment, and 3 and 12 months later. Our analyses will assess the effect of the intervention on the prevalence of at-risk drinking, the amount of drinking, and the numbers of risks identifying those subjects still considered at-risk drinkers. This study will be the first to assess a preventive intervention to reduce risks of alcohol use, alone or in conjunction with comorbidity and medication use among older adults in primary care. If such an intervention is successful, potentially hundreds of thousands of older persons may benefit from a reduction in their risks associated with alcohol use and prevention of harm. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PROTEINS OF COAGULATION PATHWAYS Principal Investigator & Institution: Griffin, John H.; Professor; Scripps Research Institute Tpc7 La Jolla, Ca 92037 Timing: Fiscal Year 2004; Project Start 01-JUL-1992; Project End 30-JUN-2009 Summary: (provided by applicant): This project will extend the principal investigator's basic and clinical research on regulation of blood coagulation involving studies of protein-protein and protein-lipid interactions and on translational clinical research studies of venous thrombosis risk factors. Thrombosis is strongly linked to failure to regulate thrombin generation, i.e., to an imbalance in anticoagulant and procoagulant mechanisms. One major goal of this project is to elucidate molecular interactions that are critical for thrombin generation. We hypothesize that molecular mechanisms for regulation of thrombin generation by the blood coagulation pathways are determined by specific amino acids on surfaces of coagulation factors V (fV) and X (fX) and by specific lipids that determine the assembly of the procoagulant prothrombinase complex (fXa:fVa:phospholipid:Ca++). Preliminary data from synthetic peptides that inhibit fVa or fXa functions combined with analysis of fVa and fXa three-dimensional structures enable us to propose specific mutations in fVa and fXa that we speculate will cause loss of functional activities. In specific aims 1-4, the fVa and fXa mutants will be studied using coagulation and prothrombinase assays and fluorescence spectroscopy to identify dysfunctional molecules and to characterize the nature of their dysfunction. Based on preliminary data showing that sphingosine and other long chain alkyl amines are potent anticoagulants, we propose to clarify how sphingosine inhibits thrombin generation by neutralizing the prothrombinase complex activity. A second major goal involves translational thrombosis research. As in the previous period of support, we propose continued studies that build a bridge between plasma dyslipoproteinemia research and blood coagulation research. Based on preliminary data, we propose studies to test the hypothesis that risk of excessive thrombin generation in vivo, manifested as venous thrombosis, is associated with HDL2b deficiency and that this is caused by genetic variations (SNPs) in genes that regulate lipoprotein and HDL metabolism. The proposed studies will increase our insights into the pathophysiology of thrombosis and are likely to improve diagnosis and treatment of thrombosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: REGULATION OF BRAIN THROMBOSIS IN STROKE MODELS Principal Investigator & Institution: Zlokovic, Berislav V.; Professor and Associate Chair; Neurosurgery; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2002; Project Start 15-JUL-1999; Project End 30-JUN-2004 Summary: Human strokes are most often caused by thrombosis or thromboembolism. Abnormalities in coagulation and fibrinolysis are risk factors for ischemic stroke and brain infarction. Recent studies suggest a major role of cerebral vasculature in regulating antithrombotic, procoagulant and fibrinolytic pathways in brain. Generation of endogenous anticoagulant activated protein C (APC) is triggered by ischemia in preliminary studies. We have initially developed a mouse stroke model with fibrin-rich microvascular deposits and obstructions due to middle cerebral artery occlusion/reperfusion or thrombin-induced thromboembolism. Treatment with APC was protective in this thromboembolic model in wild type mice and in hypercoagulable mice lacking tissue plasminogen activator (tPA-/-). The in vitro anticoagulant activities of plasma protein S and APC are enhanced by high density lipoproteins (HDL). Our central hypothesis is that fibrolytic and anticoagulant mechanisms in brain and systemic
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Anticoagulants
circulation control the development of cerebrovascular thrombosis which has a major impact on functional and neuropathological outcome of focal cerebral ischemia. We hypothesize that therapeutic interventions with various natural anticoagulants (i.e., APC, protein S and HDL) or with combined anticoagulant and fibrinolytic (i.e., tPA) agents are protective and/or preventive in stroke. Wild type mice and hypercoagulable mice due to tPA(-/-) or uPA(-/-) or thrombomodulin (TM) functional homozygous knockout (TM/Pro) or protein C (+1-) heterozygosity will be subjected to stroke. Brain injury, local blood flow, neurologic outcome, deposition of fibrin, risk for hemorrhage and blood-brain barrier permeability will be studied. To test our hypothesis we propose to develop a mouse stroke model with definition of pathophysiological consequences of ischemic stroke in wild type mice and in various hypercoagulable mice (aim 1), and to determine the efficacy and safety of anticoagulant (APC, protein S and/or HDL) treatment (aim 2) and of tPA alone treatment and of combined treatment with APC, protein S and HDL (aim 3) after focal ischemic insult in wild type mice and in various hypercoagulable knockout mice. Proposed studies will define the role of hypercoagulable state in ischemic stroke and evaluate potential protective vs. deleterious effects of anticoagulant and fibrinolytic therapies for stroke. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MONOCYTES
REGULATION
OF
INDUCIBLE
GENE
EXPRESSION
IN
Principal Investigator & Institution: Mackman, Nigel; Associate Professor; Scripps Research Institute Tpc7 La Jolla, Ca 92037 Timing: Fiscal Year 2002; Project Start 01-JUL-1992; Project End 31-MAR-2006 Summary: Gram-negative sepsis is a major cause of death in intensive care units in the United States. Sepsis is induced by the presence of pathogenic bacteria in the blood. Monocytes of the host innate immune system orchestrate a rapid response to bacterial lipopolysaccharide (LPS [endotoxin]) by expressing various cytokines and by expressing the procoagulant protein tissue factor (TF), which initiates disseminated intravascular coagulation. Recent studies indicate that administration of anticoagulants reduces mortality in patients with severe sepsis. The long-term objectives of this proposal are to elucidate the mechanism by which coagulation proteases contribute to inflammation during sepsis. Our central hypothesis is that FXa activation of protease activated receptor 2 (PAR-2) enhances IL-6 expression and increases lethality during sepsis. We will also determine the role of thrombin (FIIa) -PAR- 1 signaling in sepsis. We will employ selective inhibitors of FXa and FIIa and analyze PAR-1- and PAR-2-dependent mice in a lethal mouse model of sepsis. In addition, we will use bone marrow transplantation to determine the role of TF and PAR-1 expression on monocytes versus endothelial cells in sepsis. Finally, we will generate mice that constitutively or inducibly express PAR-2 in endothelial cells to directly test our central hypothesis that PAR-2 is a key component of a pathogenic pathway involved in lethal sepsis. These studies should define the mechanism by which coagulation proteases enhance inflammation during sepsis. The clinical relevance of these studies is that they may provide new insight that can be used to develop improved therapeutic strategies for the treatment of patients with severe sepsis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: LIPOCALINS
STRUCTURE/FUNCTION
STUDIES
OF
21
ANTIHEMOSTATIC
Principal Investigator & Institution: Montfort, William R.; Professor; Biochem and Molecular Biophysics; University of Arizona P O Box 3308 Tucson, Az 857223308 Timing: Fiscal Year 2002; Project Start 01-MAR-1999; Project End 29-FEB-2004 Summary: The saliva of blood-feeding insects contains a variety of antihemostatic agents that aid in obtaining an uninterrupted flow of blood to the mouthparts. These include vasodilators, platelet aggregation inhibitors, and anticoagulants. Most of these substances are proteinaceous, and a number of their targets have been identified. However, the molecular mechanisms for their actions and the structural features responsible for their activity are largely unknown. This proposal focuses on two types of antihemostatic agents from the saliva of the triatomine bug Rhodnius prolixus, the anticoagulant nitrophorin 2 and three proteins known as salivary antiplatelet lipocalins (SAPLs). Nitrophorins are a group of four multifunctional hemeproteins which transport nitric oxide and bind histamine. Nitrophorin 2 is the only member of the group possessing anticoagulant activity as well. SAPLs 1-3 inhibit collagen-mediated platelet aggregation and thrombin activity. Surprisingly, both the nitrophorins and SAPLs belong to the lipocalin protein family despite their completely different activities. The hypotheses tested in these studies are that the anticoagulant activity of nitrophorin 2 and the antiplatelet activity of SAPLs 1-3 are due to interaction of these molecules with specific proteinaceous targets or binding of essential ligands. The specific aims of the study are to analyze the mechanisms and structural determinants of activity of nitrophorin 2 and SAPLs 1-3 using functional assays, X-ray crystallography, and sitedirected mutagenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STRUCTURE-FUNCTION CARBOXYLASE
ANALYSIS
OF
THE
GAMMA-
Principal Investigator & Institution: Berkner, Kathleen L.; Assistant Professor; Cleveland Clinic Foundation 9500 Euclid Ave Cleveland, Oh 44195 Timing: Fiscal Year 2003; Project Start 01-APR-1997; Project End 30-NOV-2006 Summary: (provided by applicant): Vitamin K dependent (VKD) proteins require carbolylation for activity and so the VKD carboxylase plays a critical role in hemostasis. The carboxylase converts Glu's to Gla's using the energy of vitamin K oxygenation. At least 10 different VKD proteins in liver engage a single carboxylase in the endoplasmic reticulum to become fully carboxylated (9-12 Gla's per molecule). Under normal conditions full carboxylation occurs, however how the process is regulated to achieve such remarkable fidelity is not known. A method that mimics the normal physiological process was developed to study protein carboxylation, which showed conclusively that carboxylase processivity can account for comprehensive carboxylation in vivo and also provided new insights into the mechanism. The carboxylase active site was identified in studies that led to a hypothesis of substrate-regulated carboxylation. The long standing question of why carboxylation is saturated when VKD proteins are expressed in mammalian cells was addressed and showed the importance of the secretory machinery in facilitating carboxylation. Two modifications, carboxylase carboxylation and phosphorylation, were discovered. The long term goal is to understand the mechanism of carboxylation, including how multiple VKD proteins compete for one carboxylase in tissue to become fully carboxylated. The specific aims proposed for the next funding period are to: 1) Determine how the active site facilitates carboxylation. The hypotheses
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Anticoagulants
for how carboxylation is regulated will be tested by characterizing a newly discovered second site of VKD protein-carboxylase interaction and determining how vitamin K is oxygenated to initiate carboxylation. 2) Define the mechanism of VKD protein carboxylation, The hypothesis that vitamin K availability, competing VKD proteins and carboxylase carboxylation affect carboxylase processivity will be tested. 3) Determine how carboxylase carboxylation and phosphorylation regulate carboxylation. The hypothesis that these modifications regulate how secretory events facilitate carboxylation will be tested by analyzing effects on carboxylase trafficking, stability, chaperone association and fIX carboxylation. These studies will make fundamental contributions towards understanding the mechanism of carboxylation, which will be important for developing improved anticoagulants, determining how changes in diet and anticoagulation affect hemostasis and producing therapeutic amounts of VKD proteins. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SYNDROME
THERAPY
WITH
ANNEXINS
FOR
ANTIPHOSPHOLIPID
Principal Investigator & Institution: Campos-Naciff, Maria-Begona M.; Molecular and Cellular Physio; University of Cincinnati 2624 Clifton Ave Cincinnati, Oh 45221 Timing: Fiscal Year 2002; Project Start 08-MAY-2001; Project End 30-APR-2005 Summary: (Scanned from the applicant's description): APS is a disorder characterized by venous and arterial thrombosis, recurrent fetal loss, thrombocytopenia and by the presence of antiphospholipid antibodies. Recurrent pregnancy loss is produced also in APS patients due to thrombosis in the placental vasculature. Patients with APS also have higher risks of other obstetric and postnatal complications like preeclampsia, fetal distress, fetal growth impairment, premature delivery, maternal postpartum thrombosis and postpartum lung syndrome. In vitro, the annexins, a family of calcium dependent membrane binding proteins, are extremely potent inhibitors of blood coagulation. Annexin V has been proposed to regulate thrombosis and homeostasis on the villous trophoblast surface by shielding the anionic phospholipid membrane that may accelerate the coagulation cascade whereas the antiphospholipid antibodies have been proposed to displace the annexin V shield, causing exposure of phospholipid surfaces that produce activation in the coagulation cascade. Therefore, our initial hypothesis is that annexins could act in vivo as potent anticoagulants and could be beneficial in treating APS. In this study, we will evaluate therapeutic potential of wild type annexin V and mutants annexin V in vivo. Our prediction is that annexin mutants with higher affinity for phospholipid membranes may act as better anticoagulants. To test this hypothesis annexin V mutants will be created. The phospholipid binding affinity of wild type annexin and mutated annexin V will be compared with the antiphospholipid antibodies using three distinct approaches. Using a pregnant mice model, we will evaluate the therapeutic potential of these in vivo against the pathological effects of the antiphospholipid antibodies. Mice will be evaluated for fetal viability and size, fetal loss, placental thrombosis in the fetal and in the maternal side. We predict that annexin V may ameliorate the pathological consequences of the infusion of an antiphospholipid antibody. Transgenic mice will be used to evaluate the potential therapeutic of extracellular annexin V in the context of the whole animal. The results obtained with this work will provide useful treatment strategies to ameliorate the symptoms associated with the antiphospholipid syndrome. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: TICK VACCINE PREVENTION OF LYME BORRELIOSIS Principal Investigator & Institution: Kantor, Fred S.; Associate Professor; Internal Medicine; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2003; Project Start 15-MAR-2003; Project End 28-FEB-2007 Summary: (provided by applicant): Our strategy is to prevent transmission of Lyme borreliosis by interfering with the tick's ability to feed to repletion. The proposed project attempts to identify and characterize a family of anticoagulants used by Ixodes ticks needed to permit feeding on their mammalian hosts. Such anticoagulants are vital to the success of tick feeding and in the transmission on tick borne pathogens. We shall explore the family of Ixodes tick anticoagulants by biochemical separation from tick salivary gland and saliva, and by probing cDNA and genomic libraries with appropriate primer fragments. Previous attempts in our laboratories to isolate tick salivary proteins by probing cDNA libraries with antibodies from animals made tick immune resulted in 40 clones; 22 of which were represented by an anticoagulant that we have called SALP14. In the present proposal we will probe libraries with primers derived from homologous portions of the clones previously identified in order to characterize what we now recognize as a family of anticoagulants vital to tick feeding and transmission of Lyme borreliosis. We will express and purify the recombinant anticoagulants and characterize their activities. To determine active sites, we will generate deletion mutants of these anticoagulants and identify the smallest region essential for effective catalytic activity, as well as antigenicity. The goal is to interfere with feeding by the immune response directed against the functional epitope(s) of the anticoagulant molecules. Feeding to repletion is essential for ticks to complete their life cycle and for the transmission of the pathogens they harbor. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: TOWARDS THE DEVELOPMENT OF PEDIATRIC STROKE TRIALS Principal Investigator & Institution: Pavlakis, Steven G.; Professor; Maimonides Medical Center (Brooklyn) 4802 10Th Ave New York, Ny 112192844 Timing: Fiscal Year 2004; Project Start 01-JUL-2004; Project End 30-JUN-2005 Summary: (provided by applicant): Childhood stroke is a serious and frequent which affects over 6/100,000 children / year and has a ten percent mortality. Adverse outcomes include neurological deficits or seizures in 70% and recurrent strokes in 20%. In adults, clinical trials provide evidence based specialized and standardized approaches to treatment. The adult trial conclusions may have limited value in children based on differences in pathophysiology. Pediatric stroke is at an early stage of research development with no randomized clinical trials (RCT) except in sickle cell disease and few epidemiological studies. The requisite data and collaboration for pediatric stroke trials is being obtained through a 2 year multi-center study initiated by the applicants and funded in 2002 by the CNS/CNF entitled "Towards the Establishment of Standards of Practice and the Initiation of Multi-Center, Multi-National Clinical Trials for Neonates and Children with Stroke". This grant arose from an initial NINDS funded meeting in 2000 at which researchers met and developed a 15 center study. This 2 year consecutive cohort study which will be completed in December 2004 is providing data which will enable RCT's including diagnostic definitions, risk factors, current treatments and outcomes. It is now crucial to go the next step, in organizing a meeting, as proposed here, to bring together neurologists, epidemiologists and the FDA with experience in designing adult stroke and pediatric trials with key members of the pediatric neurology and epidemiology researchers to design childhood RCT's. The specific aims are to apply
24
Anticoagulants
the experience gleaned from adult stroke trials, and to discuss feasibility, potential design and prioritization of candidate studies, eg 1) RCT of anticoagulants vs. aspirin in secondary prevention of ischemic stroke; 2) intra-arterial tPA in older children with arterial ischemic stroke, and 3) low-molecular weight heparin vs. supportive therapy in neonates with non-hemorrhagic sinus thrombosis. A 3 day meeting is proposed at Glen Cove NY in September 2004. Day 1 will focus on relevant animal and adult stroke research, Day 2 will focus on available data in childhood stroke on: natural history, outcome measures, protection of patients, education strategies to promote early referral for acute therapies, pediatric safety data for tPA and other treatments, and sickle stroke trials. Day 3 will consist of working groups collating information from Days 1 and 2 into specific plans for at least 2 pediatric stroke clinical trials to be developed as grant applications. Participants will include adult stroke and sickle cell disease trialists, translational researchers and co-investigators of the international pediatric stroke study described above. 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 956165200 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
Studies
25
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
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 “anticoagulants” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for anticoagulants in the PubMed Central database: •
A circulating anticoagulant in gamma-1A-multiple myeloma: its modification by penicillin. by Glueck HI, Hong R.; 1965 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=289687
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An Allosteric Switch Controls the Procoagulant and Anticoagulant Activities of Thrombin. by Dang QD, Vindigni A, Cera ED.; 1995 Jun 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=41625
•
Ancylostoma Caninum Anticoagulant Peptide: A Hookworm-Derived Inhibitor of Human Coagulation Factor Xa. by Cappello M, Vlasuk GP, Bergum PW, Huang S, Hotez PJ.; 1995 Jun 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=41660
•
Antiplatelet and anticoagulant therapy in elective percutaneous coronary intervention. by ten Berg JM, Plokker HW, Verheugt FW.; 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=59637
•
Chemical synthesis and spontaneous folding of a multidomain protein: Anticoagulant microprotein S. by Hackeng TM, Fernandez JA, Dawson PE, Kent SB, Griffin JH.; 2000 Dec 19; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=18873
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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•
Comparing the quality of oral anticoagulant management by anticoagulation clinics and by family physicians: a randomized controlled trial. by Wilson SJ, Wells PS, Kovacs MJ, Lewis GM, Martin J, Burton E, Anderson DR.; 2003 Aug 19; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=180652
•
CONTROL OF ANTICOAGULANTS DURING OPEN HEART SURGERY. by Attar S, Rivera R, Wilson D, McLaughlin JS.; 1978 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=287701
•
Effect of anticoagulants on binding and neutralization of lipopolysaccharide by the peptide immunoglobulin conjugate CAP18(106-138)-immunoglobulin G in whole blood. by Ogata M, Fletcher MF, Kloczewiak M, Loiselle PM, Zanzot EM, Vermeulen MW, Warren HS.; 1997 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=175298
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Effects of anticoagulants and storage of blood samples on efficacy of the polymerase chain reaction assay for hepatitis C virus. by Wang JT, Wang TH, Sheu JC, Lin SM, Lin JT, Chen DS.; 1992 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=265150
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Effects of Anticoagulants and Temperature on Expression of Activation Markers CD11b and HLA-DR on Human Leukocytes. by Shalekoff S, Page-Shipp L, Tiemessen CT.; 1998 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95642
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Effects of two blood culture anticoagulants on growth of Neisseria meningitidis. by Rintala L, Pollock HM.; 1978 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=274957
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Endothelium-specific loss of murine thrombomodulin disrupts the protein C anticoagulant pathway and causes juvenile-onset thrombosis. by Isermann B, Hendrickson SB, Zogg M, Wing M, Cummiskey M, Kisanuki YY, Yanagisawa M, Weiler H.; 2001 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=209404
•
Enhancement of rabbit protein S anticoagulant cofactor activity in vivo by modulation of the protein S C4B binding protein interaction. by Weinstein RE, Walker FJ.; 1990 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=329828
•
Familial thrombophilia due to a previously unrecognized mechanism characterized by poor anticoagulant response to activated protein C: prediction of a cofactor to activated protein C. by Dahlback B, Carlsson M, Svensson PJ.; 1993 Feb 1; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=45799
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•
Immunologic Differentiation of Classic Hemophilia (Factor VIII Deficiency) and von Willebrand's Disease. WITH OBSERVATIONS ON COMBINED DEFICIENCIES OF ANTIHEMOPHILIC FACTOR AND PROACCELERIN (FACTOR V) AND ON AN ACQUIRED CIRCULATING ANTICOAGULANT AGAINST ANTIHEMOPHILIC FACTOR. by Zimmerman TS, Ratnoff OD, Powell AE.; 1971 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=291913
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Interaction of the Anticoagulant Drug Warfarin and Its Metabolites with Human Plasma Albumin. by O'Reilly RA.; 1969 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=322205
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Leflunomide can potentiate the anticoagulant effect of warfarin. by Lim V, Pande I.; 2002 Dec 7; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=137810
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Multivariate relationships between international normalized ratio and vitamin Kdependent coagulation-derived parameters in normal healthy donors and oral anticoagulant therapy patients. by Watala C, Golanski J, Kardas P.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=317378
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Normal levels of anticoagulant heparan sulfate are not essential for normal hemostasis. by HajMohammadi S, Enjyoji K, Princivalle M, Christi P, Lech M, Beeler D, Rayburn H, Schwartz JJ, Barzegar S, de Agostini AI, Post MJ, Rosenberg RD, Shworak NW.; 2003 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=152578
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Occurrence and quality of anticoagulant treatment of chronic atrial fibrillation in primary health care in Sweden: a retrospective study on electronic patient records. by Nilsson GH, Bjorholt I.; 2004; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=368440
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The anticoagulant activation of antithrombin by heparin. by Jin L, Abrahams JP, Skinner R, Petitou M, Pike RN, Carrell RW.; 1997 Dec 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=25092
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The Role of Proaccelerin in Human Blood Coagulation. Evidence that Proaccelerin Is Converted to a Prothrombin-converting Principle by Activated Stuart Factor: With Notes on the Anticoagulant Action of Soybean Trypsin Inhibitor, Protamine Sulfate, and Hexadimethrine Bromide. by Breckenridge RT, Ratnoff OD.; 1965 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=292478
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Tsetse thrombin inhibitor: Bloodmeal-induced expression of an anticoagulant in salivary glands and gut tissue of Glossina morsitans morsitans. by Cappello M, Li S, Chen X, Li CB, Harrison L, Narashimhan S, Beard CB, Aksoy S.; 1998 Nov 24; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=24366
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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 anticoagulants, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “anticoagulants” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for anticoagulants (hyperlinks lead to article summaries): •
A simple method to discriminate between beta2-glycoprotein I- and prothrombindependent lupus anticoagulants. Author(s): Simmelink MJ, Derksen RH, Arnout J, De Groot PG. Source: Journal of Thrombosis and Haemostasis : Jth. 2003 April; 1(4): 740-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12871410
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Accidental detection of lupus anticoagulants in children. Author(s): Venugopalan P, Bushra R, Gravell D. Source: Annals of Tropical Paediatrics. 2001 September; 21(3): 277-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11579869
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Adult respiratory distress syndrome: do selective anticoagulants help? Author(s): Idell S. Source: American Journal of Respiratory Medicine : Drugs, Devices, and Other Interventions. 2002; 1(6): 383-91. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14720025
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An update on new anticoagulants. Author(s): Linkins LA, Weitz JI. Source: Current Drug Targets. Cardiovascular & Haematological Disorders. 2003 December; 3(4): 287-300. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14683471
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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•
Antibiotics and anticoagulants: beware when prescribing concurrently. Author(s): Bhatt V, Moss C. Source: The British Journal of Oral & Maxillofacial Surgery. 2001 April; 39(2): 163-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11286459
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Anticoagulants (heparin, low molecular weight heparin and oral anticoagulants) for intermittent claudication. Author(s): Cosmi B, Conti E, Coccheri S. Source: Cochrane Database Syst Rev. 2001; (3): Cd001999. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11687006
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Anticoagulants (thrombin inhibitors) and aspirin synergize with P2Y12 receptor antagonism in thrombosis. Author(s): Andre P, LaRocca T, Delaney SM, Lin PH, Vincent D, Sinha U, Conley PB, Phillips DR. Source: Circulation. 2003 November 25; 108(21): 2697-703. Epub 2003 Nov 03. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14597584
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Anticoagulants and antiplatelet agents in acute ischaemic stroke. Author(s): Bath P. Source: Lancet. Neurology. 2002 November; 1(7): 405. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12849358
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Anticoagulants and blood thinners during cutaneous surgery: always, sometimes or never? Author(s): Schanbacher CF. Source: Skin Therapy Letter. 2004 March; 9(3): 5-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15037926
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Anticoagulants and inhibitors of platelet aggregation derived from leeches. Author(s): Salzet M. Source: Febs Letters. 2001 March 16; 492(3): 187-92. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11257492
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Anticoagulants for acute respiratory distress syndrome: can they work? Author(s): Idell S. Source: American Journal of Respiratory and Critical Care Medicine. 2001 August 15; 164(4): 517-20. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11520709
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Anticoagulants for deep venous thrombosis. Author(s): Cundiff DK. Source: Journal of the Royal Society of Medicine. 2001 November; 94(11): 608-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11691907
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Anticoagulants for nonvalvular atrial fibrillation (NVAF)--drug review. Author(s): Cundiff DK. Source: Medgenmed [electronic Resource] : Medscape General Medicine. 2003 February 6; 5(1): 4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12827065
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Anticoagulants for prophylaxis and treatment of thromboembolic events. Author(s): Talarico L. Source: Blood. 2002 March 15; 99(6): 2279-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11902143
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Anticoagulants in thrombosis and cancer: the missing link. Author(s): Mousa SA. Source: Seminars in Thrombosis and Hemostasis. 2002 February; 28(1): 45-52. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11885025
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Anticoagulants interfere with PCR used to diagnose invasive aspergillosis. Author(s): Garcia ME, Blanco JL, Caballero J, Gargallo-Viola D. Source: Journal of Clinical Microbiology. 2002 April; 40(4): 1567-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11923400
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Anticoagulants or antiplatelet therapy for non-rheumatic atrial fibrillation and flutter. Author(s): Segal JB, McNamara RL, Miller MR, Powe NR, Goodman SN, Robinson KA, Bass EB. Source: Cochrane Database Syst Rev. 2001; (1): Cd001938. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11279741
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Anticoagulants versus antiplatelet agents for acute ischemic stroke. Author(s): Hankey GJ, Berge E, Sandercock P. Source: Stroke; a Journal of Cerebral Circulation. 2003 June; 34(6): 1571-2. Epub 2003 May 22. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12764231
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Are anticoagulants better than antiplatelet agents for treatment of acute ischemic stroke? Author(s): Griffin G. Source: American Family Physician. 2003 October 1; 68(7): 1307-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14567484
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Basis for using anticoagulants in coronary artery disease. Author(s): Vigran IM. Source: Postgraduate Medicine. 1969 February; 45(2): 75-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5763383
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Beta 2-glycoprotein I is a requirement for anticardiolipin antibodies binding to activated platelets: differences with lupus anticoagulants. Author(s): Shi W, Chong BH, Chesterman CN. Source: Blood. 1993 March 1; 81(5): 1255-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8443387
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Beta-2-glycoprotein I dependent lupus anticoagulants form stable bivalent antibody beta-2-glycoprotein I complexes on phospholipid surfaces. Author(s): Arnout J, Wittevrongel C, Vanrusselt M, Hoylaerts M, Vermylen J. Source: Thrombosis and Haemostasis. 1998 January; 79(1): 79-86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9459328
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Bilateral extradural hematomas in a thrombocytopenic infant receiving anticoagulants: case report. Author(s): Grabel JC, Sacher M, Rothman AS. Source: Neurosurgery. 1989 November; 25(5): 828-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2586737
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Bilateral intrarenal hematomas from anticoagulants. Author(s): Hidvegi RS. Source: J Can Assoc Radiol. 1976 December; 27(4): 250-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=993238
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Binding of coumarin anticoagulants to human and bovine serum albumin. Circular dichroism studies. Author(s): Brown NA, Muller WE. Source: Pharmacology. 1978; 17(4): 233-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=567809
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Binding specificity of lupus anticoagulants and anticardiolipin antibodies. Author(s): McNeil HP, Chesterman CN, Krilis SA. Source: Thrombosis Research. 1988 December 15; 52(6): 609-19. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3148207
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Bleeding diverticulosis in patients on oral anticoagulants. Author(s): Parsa F, Wilson SE. Source: American Journal of Surgery. 1974 June; 127(6): 708-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4545538
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Bleeding risks, risk factors and management of bleeding complications after treatment with anticoagulants, specific antithrombins, thrombolytics IIb-IIIa receptor blockers. Author(s): Armstrong PW, Mant MJ. Source: European Heart Journal. 1995 November; 16 Suppl L: 75-80. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8869023
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Blood lead determinations by atomic absorption spectrophotometry, with use of the Delves sampling-cup technique: effect of various anticoagulants. Author(s): Elfbaum SG, Juliano R, Macfarland RE, Pfeil DL. Source: Clinical Chemistry. 1972 March; 18(3): 316. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4623196
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Blood viscometry: comparison of two instruments and two anticoagulants. Author(s): Bate H, Grande MJ. Source: Medical & Biological Engineering & Computing. 1979 March; 17(2): 177-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=312394
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Blue toe syndrome: treatment with anticoagulants and delayed percutaneous transluminal angioplasty. Author(s): Brewer ML, Kinnison ML, Perler BA, White RI Jr. Source: Radiology. 1988 January; 166(1 Pt 1): 31-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2962224
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Bone image detection of lesions induced by self-administered anticoagulants. Author(s): Polga JP, Spencer RP. Source: Clinical Nuclear Medicine. 1985 August; 10(8): 592. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4042511
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Cancer, thrombosis, and anticoagulants. Author(s): Ornstein DL, Zacharski LR. Source: Current Opinion in Pulmonary Medicine. 2000 July; 6(4): 301-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10912637
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Carotid and vertebral-basilar transient ischemic attacks: effect of anticoagulants, hypertension, and cardiac disorders on survival and stroke occurrence--a population study. Author(s): Whisnant JP, Cartlidge NE, Elveback LR. Source: Annals of Neurology. 1978 February; 3(2): 107-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=655661
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Cerebral venous thrombosis: anticoagulants or thrombolyic therapy? Author(s): Benamer HT, Bone I. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2000 October; 69(4): 42730. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10990497
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Chronic use of anticoagulants. Psychosocial adaptation. Author(s): Griffith EE, Hero N 3rd. Source: N Y State J Med. 1979 January; 79(1): 90-2. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=282478
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Cimetidine and oral anticoagulants. Author(s): Flind AC. Source: British Medical Journal. 1978 November 11; 2(6148): 1367. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=719395
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Cimetidine and oral anticoagulants. Author(s): Flind AC. Source: Lancet. 1978 November 11; 2(8098): 1054. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=82071
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Cimetidine: interaction with oral anticoagulants in man. Author(s): Serlin MJ, Sibeon RG, Mossman S, Breckenridge AM, Williams JR, Atwood JL, Willoughby JM. Source: Lancet. 1979 August 18; 2(8138): 317-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=89387
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Circulating anticoagulants. Author(s): Gleicher N, Deppe G. Source: American Journal of Obstetrics and Gynecology. 1979 April 15; 133(8): 941. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=434047
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Clinical pharmacokinetics of oral anticoagulants. Author(s): Kelly JG, O'Malley K. Source: Clinical Pharmacokinetics. 1979 January-February; 4(1): 1-15. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=369763
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Clinical trial of brinase and anticoagulants as a method of treatment for advanced limb ischemia. Author(s): Verhaeghe R, Verstraete M, Schetz J, Vanhove P, Suy R, Vermylen J. Source: European Journal of Clinical Pharmacology. 1979 September; 16(3): 165-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=387420
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Combined effects of eptifibatide and anticoagulants: differences between LMWH and UH or rH in thrombin generation inhibition but not in platelet aggregation inhibition. Author(s): Koestenberger M, Gallistl S, Cvirn G, Roschitz B, Petritsch M, Leschnik B, Muntean W. Source: Thrombosis and Haemostasis. 2002 December; 88(6): 1012-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12529753
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Comparative pharmacokinetics of coumarin anticoagulants L: Physiologic modeling of S-warfarin in rats and pharmacologic target-mediated warfarin disposition in man. Author(s): Levy G, Mager DE, Cheung WK, Jusko WJ. Source: Journal of Pharmaceutical Sciences. 2003 May; 92(5): 985-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12712418
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Comparative pharmacokinetics of coumarin anticoagulants XXXV: Examination of possible pharmacokinetic interaction between (R)-(+)- and (S)-(--)-warfarin in humans. Author(s): Levy G, O'Reilly RA, Wingard LB Jr. Source: Journal of Pharmaceutical Sciences. 1978 June; 67(6): 867-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=660478
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Comparison of 2 hemostatic agents for the prevention of postextraction hemorrhage in patients on anticoagulants. Author(s): Halfpenny W, Fraser JS, Adlam DM. Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 2001 September; 92(3): 257-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11552140
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Compartment syndrome of the forearm following radial-artery puncture in a patient treated with anticoagulants. Author(s): Halpern AA, Mochizuki R, Long CE 3rd. Source: The Journal of Bone and Joint Surgery. American Volume. 1978 December; 60(8): 1136-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=721868
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Compliance and stability of INR of two oral anticoagulants with different half-lives: a randomised trial. Author(s): Laporte S, Quenet S, Buchmuller-Cordier A, Reynaud J, Tardy-Poncet B, Thirion C, Decousus H, Mismetti P. Source: Thrombosis and Haemostasis. 2003 March; 89(3): 458-67. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12624628
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Conceptions and misconceptions in testing for lupus anticoagulants. Author(s): Exner T. Source: Journal of Autoimmunity. 2000 September; 15(2): 179-83. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10968906
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Control of oral anticoagulants by the prothrombin time: a plea for uniformity. Author(s): Bain B, Forster T, Sleigh B. Source: The Medical Journal of Australia. 1978 November 4; 2(10): 459-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=739933
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Cost-effectiveness of oral anticoagulants versus aspirin in patients after infrainguinal bypass grafting surgery. Author(s): Oostenbrink JB, Tangelder MJ, Busschbach JJ, van Hout BA, Buskens E, Algra A, Lawson JA, Eikelboom BC; Dutch Bypass Oral anticoagulants or Aspirin (BOA) Study Group. Source: Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. 2001 August; 34(2): 254-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11496277
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Cutaneous reactions to anticoagulants. Recognition and management. Author(s): Harenberg J, Hoffmann U, Huhle G, Winkler M, Bayerl C. Source: American Journal of Clinical Dermatology. 2001; 2(2): 69-75. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11705306
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Dental extractions and anticoagulants. Author(s): Brownbill JW. Source: Aust Dent J. 2003 December; 48(4): 267-8; Author Reply 268. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14738133
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Detection of 4-hydroxycoumarin anticoagulants and their metabolites in urine as part of a systematic toxicological analysis procedure for acidic drugs and poisons by gas chromatography-mass spectrometry after extractive methylation. Author(s): Maurer HH, Arlt JW. Source: J Chromatogr B Biomed Sci Appl. 1998 September 4; 714(2): 181-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9766858
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Detection of 'antiphospholipid' antibodies: a single chromogenic assay of thrombin generation sensitively detects lupus anticoagulants, anticardiolipin antibodies, plus antibodies binding beta(2)-glycoprotein I and prothrombin. Author(s): Sheng Y, Hanly JG, Reddel SW, Kouts S, Guerin J, Koike T, Ichikawa K, Sturgess A, Krilis SA. Source: Clinical and Experimental Immunology. 2001 June; 124(3): 502-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11472415
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Detection of lupus anticoagulants. Author(s): Horellou MH, Samama MM. Source: Clinical Reviews in Allergy & Immunology. 1995 Spring; 13(1): 19-24. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7648345
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Detection of lupus-like anticoagulants by an enzyme-linked immunosorbent assay using a partial thromboplastin as antigen; a comparative study. Author(s): Arnout J, Huybrechts E, Vanrusselt M, Falcon C, Vermylen J. Source: Thrombosis and Haemostasis. 1990 August 13; 64(1): 26-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2125756
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Determination of coumarin-type anticoagulants in human plasma by HPLCelectrospray ionization tandem mass spectrometry with an ion trap detector. Author(s): Kollroser M, Schober C. Source: Clinical Chemistry. 2002 January; 48(1): 84-91. Erratum In: Clin Chem 2002 August; 48(8): 1372. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11751542
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Determination of serum liver tests during therapy with coumarin anticoagulants. Author(s): Penning-van Beest FJ, Aben KK, van Meegen E, de Man RA, Wilson JH, Stricker BH. Source: Journal of Hepatology. 1999 October; 31(4): 778-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10551407
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Determination of the plasma protein binding of the coumarin anticoagulants phenprocoumon and its metabolites, warfarin and acenocoumarol, by ultrafiltration and high-performance liquid chromatography. Author(s): de Vries JX, Volker U. Source: Journal of Chromatography. 1990 August 3; 529(2): 479-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2229265
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Development of an ELISA for autoantibodies to prothrombin showing their prevalence in patients with lupus anticoagulants. Author(s): Arvieux J, Darnige L, Caron C, Reber G, Bensa JC, Colomb MG. Source: Thrombosis and Haemostasis. 1995 October; 74(4): 1120-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8560423
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Diagnostic methodologies for circulating anticoagulants. Author(s): Exner T. Source: Thrombosis and Haemostasis. 1995 July; 74(1): 338-44. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8578481
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Different anticoagulants and platelet reactivity in cardiac surgical patients. Author(s): John LC, Rees GM, Kovacs IB. Source: The Annals of Thoracic Surgery. 1993 October; 56(4): 899-902. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8215666
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Differential effects of anticoagulants on the activation of platelets ex vivo. Author(s): Schneider DJ, Tracy PB, Mann KG, Sobel BE. Source: Circulation. 1997 November 4; 96(9): 2877-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9386152
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Dimensions of quality of life and self-monitoring therapy with oral anticoagulants-still research or everyday practice? Author(s): Wenzel T, Morsdorf S, Sibitz I, Schenck JF, Griengl H, Erdlenbruch W, Heinrich W, Krischek B, Birner P, Harenberg J. Source: Seminars in Thrombosis and Hemostasis. 1999; 25(1): 117-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10327231
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Disagreement between bedside and laboratory activated partial thromboplastin time and international normalized ratio for various novel anticoagulants. Author(s): Kemme MJ, Faaij RA, Schoemaker RC, Kluft C, Meijer P, Cohen AF, Burggraaf J. Source: Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis. 2001 October; 12(7): 583-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11685048
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Do anticoagulants improve survival in patients presenting with venous thromboembolism? Author(s): Kelly J, Hunt BJ. Source: Journal of Internal Medicine. 2003 December; 254(6): 527-39. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14641793
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Drug interaction with coumarin anticoagulants. Author(s): Kayser SR. Source: Progress in Cardiovascular Nursing. 1993 Summer; 8(1): 40-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8372087
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Drug interactions with oral anticoagulants. Author(s): Ahmad S. Source: Postgraduate Medicine. 1980 January; 67(1): 47-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7350566
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Drug-induced hepatitis: a rare complication of oral anticoagulants. Author(s): Hohler T, Schnutgen M, Helmreich-Becker I, Mayet WJ, Mayer zum Buschenfelde KH. Source: Journal of Hepatology. 1994 September; 21(3): 447-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7836716
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Drugs in pregnancy. Anticoagulants. Author(s): Gibson PS, Rosene-Montella K. Source: Best Practice & Research. Clinical Obstetrics & Gynaecology. 2001 December; 15(6): 847-61. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11800528
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Duration of anticoagulants in acute or recurrent venous thromboembolism. Author(s): Schulman S. Source: Current Opinion in Pulmonary Medicine. 2000 July; 6(4): 321-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10912640
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Effect and outcomes of the ASGE guidelines on the periendoscopic management of patients who take anticoagulants. Author(s): Gerson LB, Gage BF, Owens DK, Triadafilopoulos G. Source: The American Journal of Gastroenterology. 2000 July; 95(7): 1717-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10925974
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Effect of anti-beta2glycoprotein I Lupus Anticoagulants on fibrin polymerization and fibrinolysis. Author(s): Pengo V, Biasiolo A, Brocco T, Rampazzo P. Source: Autoimmunity. 2000; 32(1): 39-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10958174
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Effect of anticoagulants and antiplatelet agents on platelet-mediated thrombin generation. Author(s): Halfon S, Malinowski J, Sinha U. Source: Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis. 2002 December; 13(8): 715-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12441911
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Effect of anticoagulants and cell separation media as preanalytical determinants on zymographic analysis of plasma matrix metalloproteinases. Author(s): Mannello F, Luchetti F, Canonico B, Papa S. Source: Clinical Chemistry. 2003 November; 49(11): 1956-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14578336
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Effect of anticoagulants and storage temperature on the stability of receptor activator for nuclear factor-kappa B ligand and osteoprotegerin in plasma and serum. Author(s): Chan BY, Buckley KA, Durham BH, Gallagher JA, Fraser WD. Source: Clinical Chemistry. 2003 December; 49(12): 2083-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14633883
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Effect of anticoagulants and storage temperatures on stability of plasma and serum hormones. Author(s): Evans MJ, Livesey JH, Ellis MJ, Yandle TG. Source: Clinical Biochemistry. 2001 March; 34(2): 107-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11311219
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Effect of anticoagulants in colorimetric assay for basic carboxypeptidases. Author(s): Komura H, Obata K, Campbell W, Yumoto M, Shimomura Y, Katsuya H, Okada N, Okada H. Source: Microbiology and Immunology. 2002; 46(2): 115-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11939576
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Effect of anticoagulants on plasma homocysteine determination. Author(s): Caliskan S, Kuralay F, Onvural B. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 2001 July 5; 309(1): 53-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11408006
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Effect of lupus anticoagulants on INR with different thromboplastins. Author(s): Lawrie AS, Mackie IJ, Purdy G, Machin SJ. Source: Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis. 2001 April; 12(3): 221. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11414639
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Effect of lupus anticoagulants on INR with different thromboplastins. Author(s): Pui JC, Pollak ES. Source: Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis. 2000 September; 11(6): 579-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10997799
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Effects of anticoagulants and contemporary blood collection containers on aluminum, copper, and zinc results. Author(s): Frank EL, Hughes MP, Bankson DD, Roberts WL. Source: Clinical Chemistry. 2001 June; 47(6): 1109-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11375301
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Effects of incubation time, temperature, and anticoagulants on platelet aggregation in whole blood. Author(s): Qi R, Yatomi Y, Ozaki Y. Source: Thrombosis Research. 2001 February 1; 101(3): 139-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11228337
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Effects of the glycoprotein IIb/IIIa receptor antagonist c7E3 Fab and anticoagulants on platelet aggregation and thrombin potential under high coagulant challenge in vitro. Author(s): Koestenberger M, Gallistl S, Cvirn G, Roschitz B, Muntean W. Source: Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis. 2000 July; 11(5): 425-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10937803
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Efficacy of oral anticoagulants compared with aspirin after infrainguinal bypass surgery (the Dutch Bypass Oral anticoagulants or Aspirin study). Lancet 2000; 355: 346-51. Author(s): Anand SS. Source: Vascular Medicine (London, England). 2001; 6(1): 61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11358162
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Epidural and spinal anaesthesia and the use of anticoagulants. Author(s): Armstrong RF, Addy V, Breivik H. Source: Hosp Med. 1999 July; 60(7): 491, 496. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10605540
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Evaluation of argatroban and DUP 714 as anticoagulants for blood gas, electrolyte and ionized calcium analyses. Author(s): Lyon ME, Harding SR, Oosman SN, Lyon AW. Source: Scandinavian Journal of Clinical and Laboratory Investigation. 2000 February; 60(1): 19-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10757450
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Evaluation of patient knowledge regarding oral anticoagulants. Author(s): Roche-Nagle G, Chambers F, Nanra J, Bouchier-Hayes D, Young S. Source: Ir Med J. 2003 July-August; 96(7): 211-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14518585
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Evaluation of the anticoagulants EDTA and citrate, theophylline, adenosine, and dipyridamole (CTAD) for assessing platelet activation on the ADVIA 120 hematology system. Author(s): Macey M, Azam U, McCarthy D, Webb L, Chapman ES, Okrongly D, Zelmanovic D, Newland A. Source: Clinical Chemistry. 2002 June; 48(6 Pt 1): 891-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12029005
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Evaluation of the thrombin inhibitor D-phenylalanyl-L-prolyl-L-arginine chloromethylketone (PPACK) with the factor Xa inhibitor 1,5-dansyl-L-glutamyl-Lglycyl-L-arginine chloromethylketone (GGACK) as anticoagulants for critical care clinical chemistry specimens. Author(s): Lyon ME, Drobot DW, Harding SR, Lyon AW. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 1999 February; 280(1-2): 91-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10090527
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Factor V anticoagulants: clinical, biochemical, and immunological observations. Author(s): Feinstein DI, Rapaport SI, McGehee WG, Patch MJ. Source: The Journal of Clinical Investigation. 1970 August; 49(8): 1578-88. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4194089
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Factor XII determinations and lupus anticoagulants. Author(s): Jones DW, Gallimore MJ, Winter M. Source: Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis. 1997 November; 8(8): 531-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9491272
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False negative screening tests for lupus anticoagulants--an unrecognized problem? Author(s): Jacobsen EM, Wisloff F. Source: Thrombosis Research. 1996 June 1; 82(5): 445-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8771705
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Familial lupus anticoagulants. Author(s): Mackie IJ, Colaco CB, Machin SJ. Source: British Journal of Haematology. 1987 November; 67(3): 359-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3689698
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Femoral neuropathy and anticoagulants. Author(s): Butterfield WC, Neviaser RJ, Roberts MP. Source: Annals of Surgery. 1972 July; 176(1): 58-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4338821
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Fetal and neonatal outcome of exposure to anticoagulants during pregnancy. Author(s): Wong V, Cheng CH, Chan KC. Source: American Journal of Medical Genetics. 1993 January 1; 45(1): 17-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8418652
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Fibrinolytic activity in patients receiving long-term anticoagulants for myocardial infarction. Author(s): Hume R, Geoghegan M. Source: Scott Med J. 1966 April; 11(4): 128-31. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5929896
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Filling defects in the renal pelvis and ureter owing to bleeding secondary to acquired circulating anticoagulants. Author(s): Eisenberg RL, Clark RE. Source: The Journal of Urology. 1976 November; 116(5): 662-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=978826
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Filtrability of whole blood and erythrocyte suspensions under the influence of several anticoagulants. Author(s): Schroer R, Muth K. Source: Ric Clin Lab. 1981; 11 Suppl 1: 109-16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6821313
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Filum terminale ependymoma revealed by acute cauda equina compression syndrome following intratumoral and spinal subarachnoid hemorrhage in a patient on oral anticoagulants. Author(s): Malbrain ML, Kamper AM, Lambrecht GL, Hermans P, Baeck E, Verhoeven F, Wyffels G, Verbraeken H. Source: Acta Neurol Belg. 1994; 94(1): 35-43. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8140885
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Flow cytometric analysis of whole blood lysis, three anticoagulants, and five cell preparations. Author(s): Carter PH, Resto-Ruiz S, Washington GC, Ethridge S, Palini A, Vogt R, Waxdal M, Fleisher T, Noguchi PD, Marti GE. Source: Cytometry : the Journal of the Society for Analytical Cytology. 1992; 13(1): 68-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1372204
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Fragile left atrial thrombus successfully treated with anticoagulants. Author(s): Ogata C, Nakatani S, Yamagishi M. Source: Heart (British Cardiac Society). 2003 January; 89(1): 60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12482793
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Frequent development of lupus anticoagulants in critically ill patients treated under intensive care conditions. Author(s): Wenzel C, Stoiser B, Locker GJ, Laczika K, Quehenberger P, Kapiotis S, Frass M, Pabinger I, Knobl P. Source: Critical Care Medicine. 2002 April; 30(4): 763-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11940742
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Gastrointestinal endoscopy in patients taking antiplatelet agents and anticoagulants: survey of ASGE members. American Society for Gastrointestinal Endoscopy. Author(s): Kadakia SC, Angueira CE, Ward JA, Moore M. Source: Gastrointestinal Endoscopy. 1996 September; 44(3): 309-16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8885352
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Gemcitabine and the interaction with anticoagulants. Author(s): Kilgour-Christie J, Czarnecki A. Source: The Lancet Oncology. 2002 August; 3(8): 460. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12147431
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Glycolytic intermediates and adenine nucleotides of human platelets. I. The influence of ACD and EDTA anticoagulants. Author(s): Kim BK, Baldini MG. Source: Haematologia. 1972; 6(4): 447-57. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4206674
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Guide to anticoagulant therapy. Part 2: Oral anticoagulants. American Heart Association. Author(s): Hirsh J, Fuster V. Source: Circulation. 1994 March; 89(3): 1469-80. Erratum In: Circulation 1995 January 15; 91(2): A55-A56. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8124830
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Guidelines for testing and revised criteria for lupus anticoagulants. SSC Subcommittee for the Standardization of Lupus Anticoagulants. Author(s): Exner T, Triplett DA, Taberner D, Machin SJ. Source: Thrombosis and Haemostasis. 1991 March 4; 65(3): 320-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1904657
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Guidelines for use of anticoagulants. Author(s): Horton J, Williams LE. Source: Circulation. 1997 September 16; 96(6): 2099. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9323120
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Guidelines on anticoagulants and the use of locoregional anesthesia. Author(s): Vandermeulen E. Source: Minerva Anestesiol. 2003 May; 69(5): 407-11. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12768175
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Guidelines on anticoagulants and the use of LR anesthesia. Author(s): Vandermeulen E. Source: Acta Anaesthesiol Belg. 2001; 52(4): 425-9. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11799577
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Haemorrhagic and thromboembolic complications versus intensity of treatment of venous thromboembolism with oral anticoagulants. Author(s): Schulman S, Stigendal L, Jansson JH, Brohult J. Source: Acta Med Scand. 1988; 224(5): 425-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3059761
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Haemorrhagic bullae induced by oral anticoagulants. Author(s): Elis A, Lishner M, Lang R, Savin H, Ravid M. Source: Journal of Internal Medicine. 1993 December; 234(6): 615-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8258755
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Haemorrhagic complications of anticoagulants. Heparin-induced femoral neuropathy. Author(s): Kounis NG, Karatzas GE. Source: The Practitioner. 1980 July; 224(1345): 741-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6253979
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Haemostasis, anticoagulants and fibrinolysis. Author(s): Casey G. Source: Nursing Standard : Official Newspaper of the Royal College of Nursing. 2003 October 29-November 4; 18(7): 45-51; Quiz 53, 55. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14639979
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Hazards of oral anticoagulants during pregnancy. Author(s): Stevenson RE, Burton OM, Ferlauto GJ, Taylor HA. Source: Jama : the Journal of the American Medical Association. 1980 April 18; 243(15): 1549-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7359739
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Hemarthrosis and oral anticoagulants. Author(s): Neuzil KM, Morgan HJ. Source: J Tenn Med Assoc. 1991 April; 84(4): 180-1. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1865684
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Hemobilia: a possible cause of jaundice in patients receiving anticoagulants. Author(s): Jolobe OM. Source: Journal of Hepatology. 1995 May; 22(5): 597-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7650342
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Hemocultures from chronic Chagasic patients using EDTA or heparin as anticoagulants. Author(s): Galvao LM, Cancado JR, Rezende DF, Krettli AU. Source: Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Medicas E Biologicas / Sociedade Brasileira De Biofisica. [et Al.]. 1989; 22(7): 841-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2517040
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Hemodialysis without anticoagulants: efficiency and hemostatic aspects. Author(s): Casati S, Moia M, Graziani G, Cantaluppi A, Citterio A, Mannucci PM, Ponticelli C. Source: Clinical Nephrology. 1984 February; 21(2): 102-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6723110
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Hemodynamic characteristics of the composite strut ball valve prostheses (StarrEdwards track valves) in patients on anticoagulants. Author(s): McAnulty JH, Morton M, Rahimtoola SH, Kloster FE, Ahuja N, Starr AE. Source: Circulation. 1978 September; 58(3 Pt 2): I159-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14740696
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Heparin and oral anticoagulants in the treatment of brain ischemia. Author(s): Chaves CJ, Caplan LR. Source: Journal of the Neurological Sciences. 2000 February 1; 173(1): 3-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10675573
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Heparin and warfarin: use of anticoagulants in the prevention and treatment of venous thrombosis and pulmonary embolism. Author(s): Rosen RL. Source: The Journal of Family Practice. 1979 May; 8(5): 923-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=438753
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Heparin-like anticoagulants in asthma. Author(s): Lasser EC, Simon RA, Lyon SG, Hamblin AE, Stein R. Source: Allergy. 1987 November; 42(8): 619-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3425861
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Hereditary deficiency of all vitamin K-dependent procoagulants and anticoagulants. Author(s): Brenner B, Tavori S, Zivelin A, Keller CB, Suttie JW, Tatarsky I, Seligsohn U. Source: British Journal of Haematology. 1990 August; 75(4): 537-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2145029
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Herpes zoster infection and use of oral anticoagulants. A potentially dangerous association. Author(s): Blumenkopf B, Lockhart WS Jr. Source: Jama : the Journal of the American Medical Association. 1983 August 19; 250(7): 936-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6864976
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Heterogeneity and diversity of IgM and IgG lupus anticoagulants in an individual with systemic lupus erythematosus. Author(s): Nakamura N, Azuma C, Akamizu T, Sugawa H, Matsuda F, Mitsuda N, Honjo T, Mori T, Yamaji K. Source: Biochemical and Biophysical Research Communications. 1994 September 30; 203(3): 1789-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7945329
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Hirudins: antithrombin anticoagulants. Author(s): Stringer KA, Lindenfeld J. Source: The Annals of Pharmacotherapy. 1992 December; 26(12): 1535-40. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1482812
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Hospitalisation for upper gastrointestinal bleeding associated with use of oral anticoagulants. Author(s): Johnsen SP, Sorensen HT, Mellemkjoer L, Blot WJ, Nielsen GL, McLaughlin JK, Olsen JH. Source: Thrombosis and Haemostasis. 2001 August; 86(2): 563-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11522004
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How to prevent stroke recurrence in patients with patent foramen ovale: anticoagulants, antiaggregants, foramen closure, or nothing? Author(s): Nendaz M, Sarasin FP, Bogousslavsky J. Source: European Neurology. 1997; 37(4): 199-204. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9208257
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Human hybridoma lupus anticoagulants distinguish between lamellar and hexagonal phase lipid systems. Author(s): Rauch J, Tannenbaum M, Tannenbaum H, Ramelson H, Cullis PR, Tilcock CP, Hope MJ, Janoff AS. Source: The Journal of Biological Chemistry. 1986 July 25; 261(21): 9672-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3733693
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Identification of critical molecular interactions mediating heparin activation of antithrombin: implications for the design of improved heparin anticoagulants. Author(s): Olson ST, Bjork I, Bock SC. Source: Trends in Cardiovascular Medicine. 2002 July; 12(5): 198-205. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12161073
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Improved confirmation of weak lupus anticoagulants by employing sensitive and insensitive reagents to the lupus anticoagulant. Author(s): Ames PR, Iannaccone L, De Iasio R, Brancaccio V. Source: Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis. 2001 October; 12(7): 563-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11685045
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Improved detection of lupus anticoagulants by the dilute Russell's Viper venom time. Author(s): Moore GW, Savidge GF, Smith MP. Source: Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis. 2000 December; 11(8): 767-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11132656
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Improving methods to assess therapeutic quality control of treatment with oral anticoagulants. Author(s): Marco F, Sedano C, Bermudez A, Duarte ML, Zubizarreta A. Source: Thrombosis and Haemostasis. 2000 November; 84(5): 920-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11127879
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Infantile cerebellar thrombosis: a case of lupus anticoagulants? Author(s): Bardella D, Rossi ML, Temporin G. Source: Pediatr Med Chir. 2002 September-October; 24(5): 392-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12494544
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Influence of anticoagulants on the level of soluble HLA class I and class II antigens measured in blood samples. Author(s): Hausmann S, Claus R, Falk U, Wegener S. Source: J Immunoassay. 1996 August; 17(3): 257-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8842984
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Influence of citrate and EDTA anticoagulants on plasma malondialdehyde concentrations estimated by high-performance liquid chromatography. Author(s): Suttnar J, Masova L, Dyr JE. Source: J Chromatogr B Biomed Sci Appl. 2001 February 10; 751(1): 193-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11232851
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Influence of different anticoagulants on platelet aggregation in whole blood; a comparison between citrate, low molecular mass heparin and hirudin. Author(s): Wallen NH, Ladjevardi M, Albert J, Broijersen A. Source: Thrombosis Research. 1997 July 1; 87(1): 151-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9253810
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Inhibition of blood coagulation activation and oral anticoagulants in patients with mechanical heart valve prostheses. Author(s): Barcellona D, Mameli G, Marongiu F. Source: Thrombosis Research. 1996 February 1; 81(3): 403-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8928097
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Inhibition of metastases by anticoagulants. Author(s): Hejna M, Raderer M, Zielinski CC. Source: Journal of the National Cancer Institute. 1999 January 6; 91(1): 22-36. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9890167
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Interaction between anticoagulants and contraceptives: an unsuspected finding. Author(s): de Teresa E, Vera A, Ortigosa J, Pulpon LA, Arus AP, de Artaza M. Source: British Medical Journal. 1979 November 17; 2(6200): 1260-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=519402
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Interaction between clarithromycin and oral anticoagulants. Author(s): Grau E, Real E, Pastor E. Source: The Annals of Pharmacotherapy. 1996 December; 30(12): 1495-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8968465
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Interaction of dietary factors with oral anticoagulants: review and applications. Author(s): Harris JE. Source: Journal of the American Dietetic Association. 1995 May; 95(5): 580-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7722194
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Interference of lupus anticoagulants in prothrombin time assays: implications for selection of adequate methods to optimize the management of thrombosis in the antiphospholipid-antibody syndrome. Author(s): Della Valle P, Crippa L, Garlando AM, Pattarini E, Safa O, Vigano D'Angelo S, D'Angelo A. Source: Haematologica. 1999 December; 84(12): 1065-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10586206
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International normalized ratio for prothrombin times in patients taking oral anticoagulants: critical difference and probability of significant change in consecutive measurements. Author(s): Lassen JF, Brandslund I, Antonsen S. Source: Clinical Chemistry. 1995 March; 41(3): 444-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7882520
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Interpretation of Dutch BOA trial. Dutch Bypass Oral anticoagulants or Aspirin study group. Author(s): Algra A, Tangelder MJ, Lawson JA, Eikelboom BC. Source: Lancet. 2000 April 1; 355(9210): 1186-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10791406
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Intracranial bleed in a pregnant patient on oral anticoagulants for prosthetic heart valve. Author(s): Bagga R, Sawhney H, Saxena SV, Aggarwal N, Vasishta K. Source: Acta Obstetricia Et Gynecologica Scandinavica. 2001 August; 80(8): 766-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11531623
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Introduction: are natural anticoagulants candidates for modulating the inflammatory response to endotoxin? Author(s): Esmon CT. Source: Blood. 2000 February 15; 95(4): 1113-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10666178
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Is there a hypercoagulable phase during initiation of antithrombotic therapy with oral anticoagulants in patients with atrial fibrillation? Author(s): Zeuthen EL, Lassen JF, Husted SE. Source: Thrombosis Research. 2003 March 15; 109(5-6): 241-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12818245
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Is there a phospholipid specificity of lupus anticoagulants (LAC) in patients with autoimmune and drug induced LAC? Author(s): Hess EV. Source: The Journal of Rheumatology. 1998 February; 25(2): 200-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9489806
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Laboratory diagnosis of heparin-induced thrombocytopenia and monitoring of alternative anticoagulants. Author(s): Leo A, Winteroll S. Source: Clinical and Diagnostic Laboratory Immunology. 2003 September; 10(5): 731-40. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12965896
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Laboratory diagnosis of lupus anticoagulants for patients on oral anticoagulant treatment. Performance of dilute Russell viper venom test and silica clotting time in comparison with Staclot LA. Author(s): Tripodi A, Chantarangkul V, Clerici M, Mannucci PM. Source: Thrombosis and Haemostasis. 2002 October; 88(4): 583-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12362227
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Laboratory diagnosis of lupus anticoagulants--effect of residual platelets in plasma, assessed by Staclot LA and silica clotting time. Author(s): Chantarangkul V, Tripodi A, Clerici M, Bressi C, Mannucci PM. Source: Thrombosis and Haemostasis. 2002 May; 87(5): 854-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12038789
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Laboratory identification of lupus anticoagulants using the combination of activated partial thromboplastin time and Russell's viper venom at two phospholipid concentrations. Author(s): Akkawat B, Chantarangkul V, Rojnuckarin P, Juntiang J. Source: J Med Assoc Thai. 2003 June; 86 Suppl 2: S451-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12930024
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Large variations in the use of oral anticoagulants in stroke patients with atrial fibrillation: a Swedish national perspective. Author(s): Glader EL, Stegmayr B, Norrving B, Terent A, Hulter-Asberg K, Wester PO, Asplund K; Riks-Stroke Collaboration. Source: Journal of Internal Medicine. 2004 January; 255(1): 22-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14687235
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Liver damage induced by coumarin anticoagulants. Author(s): Ehrenforth S, Schenk JF, Scharrer I. Source: Seminars in Thrombosis and Hemostasis. 1999; 25(1): 79-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10327225
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Long-term use of oral anticoagulants and the risk of fracture. Author(s): Caraballo PJ, Heit JA, Atkinson EJ, Silverstein MD, O'Fallon WM, Castro MR, Melton LJ 3rd. Source: Archives of Internal Medicine. 1999 August 9-23; 159(15): 1750-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10448778
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Low levels of activated protein C in patients with systemic lupus erythematosus do not relate to lupus anticoagulants but to low levels of factor II. Author(s): Simmelink MJ, Fernandez JA, Derksen RH, Griffin JH, de Groot PG. Source: British Journal of Haematology. 2002 June; 117(3): 676-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12028041
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Low molecular weight heparin versus oral anticoagulants in the long-term treatment of deep venous thrombosis. Author(s): Lopez-Beret P, Orgaz A, Fontcuberta J, Doblas M, Martinez A, Lozano G, Romero A. Source: Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. 2001 January; 33(1): 77-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11137927
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Lupus anticoagulants and antiphospholipid antibodies. Author(s): Thiagarajan P, Shapiro SS. Source: Hematology/Oncology Clinics of North America. 1998 December; 12(6): 116792, V. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9922931
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Lupus anticoagulants are stronger risk factors for thrombosis than anticardiolipin antibodies in the antiphospholipid syndrome: a systematic review of the literature. Author(s): Galli M, Luciani D, Bertolini G, Barbui T. Source: Blood. 2003 March 1; 101(5): 1827-32. Epub 2002 October 03. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12393574
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Lupus anticoagulants form immune complexes with prothrombin and phospholipid that can augment thrombin production in flow. Author(s): Field SL, Hogg PJ, Daly EB, Dai YP, Murray B, Owens D, Chesterman CN. Source: Blood. 1999 November 15; 94(10): 3421-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10552952
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Lupus anticoagulants, thrombosis and the protein C system. Author(s): Esmon NL, Smirnov MD, Safa O, Esmon CT. Source: Haematologica. 1999 May; 84(5): 446-51. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10329924
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Lupus anticoagulants: pathogenesis and laboratory diagnosis. Author(s): Court EL. Source: British Journal of Biomedical Science. 1997 December; 54(4): 287-98. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9624740
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Management of anticoagulants during pregnancy. Author(s): Hanania G. Source: Heart (British Cardiac Society). 2001 August; 86(2): 125-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11454818
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Management of anticoagulants in a patient requiring major surgery. Author(s): Tavel ME, Stein PD. Source: Chest. 1998 December; 114(6): 1756-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9872212
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Many faces of lupus anticoagulants. Author(s): Triplett DA. Source: Lupus. 1998; 7 Suppl 2: S18-22. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9814666
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Mechanism of action of beta2-glycoprotein I-dependent lupus anticoagulants. Author(s): Arnout J, Vermylen J. Source: Lupus. 1998; 7 Suppl 2: S23-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9814667
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Mechanized amidolytic technique for determination of factor X and factor-X antigen, and its application to patients being treated with oral anticoagulants. Author(s): van Wijk EM, Kahle LH, ten Cate JW. Source: Clinical Chemistry. 1980 June; 26(7): 885-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7379310
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Metabolism of vitamin K and prothrombin synthesis: anticoagulants and the vitamin K--epoxide cycle. Author(s): Bell RG. Source: Fed Proc. 1978 October; 37(12): 2599-604. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=359368
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Methods for subtyping lupus anticoagulants. Author(s): Exner T. Source: Lupus. 1998; 7 Suppl 2: S103-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9814684
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Mild head injury, anticoagulants, and risk of intracranial injury. Author(s): Li J, Brown J, Levine M. Source: Lancet. 2001 March 10; 357(9258): 771-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11253975
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Minor oral surgical procedures in patients on oral anticoagulants. Author(s): Davies D. Source: Aust Dent J. 2003 December; 48(4): 267. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14738132
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Monitoring oral anticoagulant therapy in patients with lupus anticoagulants. Author(s): Ortel TL, Moll S. Source: British Journal of Haematology. 1998 May; 101(2): 390-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9609541
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Monitoring the effect of anticoagulants on left atrial thrombi in patients with rheumatic heart disease: assessment with 111In-oxine-labelled platelet heart scintigraphy and transoesophageal echocardiography. Author(s): Sun SS, Hsieh JF, Tsai SC, Ho YJ, Lee JK, Kao CH. Source: Nuclear Medicine Communications. 2000 July; 21(7): 627-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10994665
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Monitoring therapy with anticoagulants in The Netherlands. Author(s): Breukink-Engbers WG. Source: Seminars in Thrombosis and Hemostasis. 1999; 25(1): 37-42. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10327219
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Monitoring warfarin therapy in patients with lupus anticoagulants (LA) Author(s): Tripodi A, Mannucci PM. Source: Thrombosis and Haemostasis. 1998 August; 80(2): 349-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9716171
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Monitoring warfarin therapy in patients with lupus anticoagulants. Author(s): D'Angelo A, Della Valle P, Crippa L. Source: Annals of Internal Medicine. 1998 March 15; 128(6): 504-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9499339
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Monoclonal IgG anticoagulants delaying fibrin aggregation in two patients with systemic lupus erythematosus (SLE). Author(s): Galanakis DK, Ginzler EM, Fikrig SM. Source: Blood. 1978 November; 52(5): 1037-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=698389
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Multicenter evaluation of a new chromogenic factor X assay in plasma of patients on oral anticoagulants. Author(s): Ciavarella N, Coccheri S, Gensini GF, Hassan HJ, Mannucci PM, Manotti C, Margstakler E, Mariani G, Orlando M, Palareti G, Petronelli M, Pogliani E, Ponari O, Prisco D, Recalcati P, Rossi E, Salvitti C, Tripodi A. Source: Thrombosis Research. 1980 August 15-September 1; 19(4-5): 493-502. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7444863
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Multiple competitive displacement interactions involving human serum albumin, anticoagulants, oleic acid and various drugs. Author(s): Wosilait WD, Ryan MP. Source: General Pharmacology. 1980; 11(4): 387-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6156878
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Natural anticoagulants (antithrombin III, protein C, and protein S) in patients with mild to moderate ischemic stroke. Author(s): Haapaniemi E, Tatlisumak T, Soinne L, Syrjala M, Kaste M. Source: Acta Neurologica Scandinavica. 2002 February; 105(2): 107-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11903120
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Natural anticoagulants and the liver. Author(s): Castelino DJ, Salem HH. Source: Journal of Gastroenterology and Hepatology. 1997 January; 12(1): 77-83. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9076629
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Natural anticoagulants in smokers. Author(s): Campbell Tait R, Walker ID, Islam SI. Source: American Heart Journal. 1993 June; 125(6): 1806-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8498337
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Natural anticoagulants in systemic lupus erythematosus. Deficiency of protein S bound to C4bp associates with recent history of venous thromboses, antiphospholipid antibodies, and the antiphospholipid syndrome. Author(s): Ruiz-Arguelles GJ, Ruiz-Arguelles A, Alarcon-Segovia D, Drenkard C, Villa A, Cabiedes J, Presno-Bernal M, Deleze M, Ortiz-Lopez R, Vazquez-Prado J. Source: The Journal of Rheumatology. 1991 April; 18(4): 552-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1829765
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Natural anticoagulants, aging, and thromboembolism. Author(s): Sagripanti A, Carpi A. Source: Experimental Gerontology. 1998 November-December; 33(7-8): 891-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9951632
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Naturally occurring anticoagulants and bone marrow transplantation: plasma protein C predicts the development of venocclusive disease of the liver. Author(s): Faioni EM, Krachmalnicoff A, Bearman SI, Federici AB, Decarli A, Gianni AM, McDonald GB, Mannucci PM. Source: Blood. 1993 June 15; 81(12): 3458-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8507881
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New anticoagulants for venous thromboembolic disease. Author(s): Chang P. Source: Idrugs. 2004 January; 7(1): 50-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14730467
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New antithrombin-based anticoagulants. Author(s): Desai UR. Source: Medicinal Research Reviews. 2004 March; 24(2): 151-81. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14705167
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New aspects of the blood coagulation cascade, anticoagulants and vein thrombosis in Asia. Author(s): Gallus AS, Lee LH, Coghlan DW. Source: Ann Acad Med Singapore. 2002 November; 31(6): 685-96. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12520819
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New diagnostic strategies for lupus anticoagulants and antiphospholipid antibodies. Author(s): Triplet DA. Source: Haemostasis. 1994 May-June; 24(3): 155-64. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7988945
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New protocols for perioperative management of podiatric patients taking oral anticoagulants. Author(s): Mandracchia VJ, Evans RD, Sticha R. Source: The Journal of Foot and Ankle Surgery : Official Publication of the American College of Foot and Ankle Surgeons. 1994 September-October; 33(5): 526. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7849681
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New protocols for perioperative management of podiatric patients taking oral anticoagulants. Author(s): Lanzat M, Danna AT, Jacobson DS. Source: The Journal of Foot and Ankle Surgery : Official Publication of the American College of Foot and Ankle Surgeons. 1994 January-February; 33(1): 16-20. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8161987
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New thrombolytics, anticoagulants, and platelet antagonists: the future of clinical practice. Author(s): Becker RC. Source: Journal of Thrombosis and Thrombolysis. 1999 April; 7(2): 195-220. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10364771
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Novel anticoagulants based on direct inhibition of thrombin and factor Xa. Author(s): Gardell SJ, Sanderson PE. Source: Coronary Artery Disease. 1998; 9(2-3): 75-81. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9647407
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Novel anticoagulants based on inhibition of the factor VIIa/tissue factor pathway. Author(s): Johnson K, Hung D. Source: Coronary Artery Disease. 1998; 9(2-3): 83-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9647408
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Novel anticoagulants for flow cytometric analysis of live leucocytes in whole blood. Author(s): McCarthy DA, Macey MG. Source: Cytometry : the Journal of the Society for Analytical Cytology. 1996 March 1; 23(3): 196-204. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8974865
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Novel anticoagulants for the prevention and treatment of venous thromboembolism. Author(s): Weltermann A, Kyrle PA, Eichinger S. Source: Wiener Medizinische Wochenschrift (1946). 2003; 153(19-20): 426-33. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14648923
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N-terminal requirements of small peptide anticoagulants based on hirudin54-65. Author(s): Owen TJ, Krstenansky JL, Yates MT, Mao SJ. Source: Journal of Medicinal Chemistry. 1988 May; 31(5): 1009-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3361570
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Occlusion of the aorta and inferior vena cava in a patient with circulating anticoagulants. Author(s): DiCenta I, Fadel E, Mussot S, Paul JF, Remuzon G, Dartevelle P. Source: Annals of Vascular Surgery. 2002 May; 16(3): 380-3. Epub 2002 May 20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12016540
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Occlusive coronary thrombosis and oral anticoagulants. Author(s): Barrillon A, Kusmierek J, Gerbaux A. Source: Thrombosis and Haemostasis. 1979 February 28; 41(1): 255-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=483234
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Optimal therapeutic range for oral anticoagulants in Japanese patients with prosthetic heart valves: a preliminary report from a single institution using conversion from thrombotest to PT-INR. Author(s): Uetsuka Y, Hosoda S, Kasanuki H, Aosaki M, Murasaki K, Ooki K, Inoue M, Akiyama E, Kitada M. Source: Heart and Vessels. 2000; 15(3): 124-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11289500
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Oral anticoagulants and antithrombin III. Author(s): Frost T, Loveday D. Source: The Medical Journal of Australia. 1980 August 23; 2(4): 220. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7432294
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Oral anticoagulants and regional anesthesia for joint replacement surgery. Author(s): L'E Orme RM. Source: Regional Anesthesia and Pain Medicine. 2002 January-February; 27(1): 112-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11799520
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Oral anticoagulants in patients with coronary artery disease. Author(s): Anand SS, Yusuf S. Source: Journal of the American College of Cardiology. 2003 February 19; 41(4 Suppl S): 62S-69S. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12644343
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Prevalence and clinical features of dementia associated with the antiphospholipid syndrome and circulating anticoagulants. Author(s): Chapman J, Abu-Katash M, Inzelberg R, Yust I, Neufeld MY, Vardinon N, Treves TA, Korczyn AD. Source: Journal of the Neurological Sciences. 2002 November 15; 203-204: 81-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12417362
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Preventing complications in heparin-induced thrombocytopenia. Alternative anticoagulants are improving patient outcomes. Author(s): Rice L, Nguyen PH, Vann AR. Source: Postgraduate Medicine. 2002 September; 112(3): 85-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12360660
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Regulated endothelial cell expression of novel anticoagulants: a strategy for the prevention and therapy of intravascular thrombosis. Author(s): Dorling A, Chen D, Riesbeck K, McVey J, Kemball-Cook G, Tuddenham EG, Lechler RI. Source: Transplantation Proceedings. 2000 August; 32(5): 971. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10936303
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Reversing anticoagulants both old and new. Author(s): Warkentin TE, Crowther MA. Source: Canadian Journal of Anaesthesia = Journal Canadien D'anesthesie. 2002 JuneJuly; 49(6): S11-25. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12557411
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Review: anticoagulants may be better than antiplatelet agents for nonfatal stroke but not other vascular or fatal events in nonrheumatic AF. Author(s): Ebrahim S, Taylor F. Source: Acp Journal Club. 2001 September-October; 135(2): A17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11571899
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Risk of colonoscopic polypectomy bleeding with anticoagulants and antiplatelet agents: analysis of 1657 cases. Author(s): Hui AJ, Wong RM, Ching JY, Hung LC, Chung SC, Sung JJ. Source: Gastrointestinal Endoscopy. 2004 January; 59(1): 44-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14722546
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Routine use of adjusted low-dose oral anticoagulants during the first three postoperative months after hip fracture in patients without comorbidity factors. Author(s): Hernigou P, Charpentier P. Source: Journal of Orthopaedic Trauma. 2001 November; 15(8): 535-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11733668
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Septic cavernous sinus thrombosis secondary to sinusitis: are anticoagulants indicated? A review of the literature. Author(s): Bhatia K, Jones NS. Source: The Journal of Laryngology and Otology. 2002 September; 116(9): 667-76. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12437798
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The Ecarin time is an improved confirmatory test for the Taipan snake venom time in warfarinized patients with lupus anticoagulants. Author(s): Moore GW, Smith MP, Savidge GF. Source: Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis. 2003 April; 14(3): 307-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12695757
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Thrombophilic genotypes, natural anticoagulants, and plasma homocysteine in myeloproliferative disorders: relationship with splanchnic vein thrombosis and arterial disease. Author(s): Amitrano L, Guardascione MA, Ames PR, Margaglione M, Antinolfi I, Iannaccone L, Annunziata M, Ferrara F, Brancaccio V, Balzano A. Source: American Journal of Hematology. 2003 February; 72(2): 75-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12555209
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Treatment of cancer with anticoagulants: rationale in the treatment of melanoma. Author(s): Ornstein DL, Zacharski LR. Source: International Journal of Hematology. 2001 February; 73(2): 157-61. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11372726
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Treatment of deep vein thrombosis with oral anticoagulants in patients with malignancy: prospective cohort study. Author(s): Vucic N, Ostojic R, Svircic T. Source: Croatian Medical Journal. 2002 June; 43(3): 296-300. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12035135
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Use of different anticoagulants in test tubes for analysis of blood lactate concentrations: Part 2. Implications for the proper handling of blood specimens obtained from critically ill patients. Author(s): Wiese J, Didwania A, Kerzner R, Chernow B. Source: Critical Care Medicine. 1997 November; 25(11): 1847-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9366768
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Use of oral anticoagulants in older patients. Author(s): Sebastian JL, Tresch DD. Source: Drugs & Aging. 2000 June; 16(6): 409-35. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10939307
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Viscosity of blood in normal subjects and in patients suffering from coronary occlusion and arterial thrombosis. An in vitro study in the absence of anticoagulants, by means of a rotational cone-in-cone trolley viscometer. Author(s): Dintenfass L, Julian DG, Miller GE. Source: American Heart Journal. 1966 May; 71(5): 587-600. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5949142
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Vitamin B12-binding proteins in serum and plasma in various disorders. Effect of anticoagulants. Author(s): Carmel R. Source: American Journal of Clinical Pathology. 1978 March; 69(3): 319-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=416709
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Warfarin monitoring in patients with anticardiolipin antibodies, but without lupus anticoagulants. Author(s): Mant MJ, Stang L, Etches WS. Source: Thrombosis Research. 2000 September 1; 99(5): 477-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10973677
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Warfarin or acenocoumarol: which is better in the management of oral anticoagulants? Author(s): Barcellona D, Vannini ML, Fenu L, Balestrieri C, Marongiu F. Source: Thrombosis and Haemostasis. 1998 December; 80(6): 899-902. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9869157
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What is the risk of complications from cataract surgery in patients taking anticoagulants? Author(s): Langston RH. Source: Cleve Clin J Med. 2001 February; 68(2): 97-8. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11220461
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What is the role of oral anticoagulants and platelet inhibitors in peripheral vascular surgery? Author(s): Van Urk H, Kretschmer GJ. Source: Eur J Vasc Surg. 1990 December; 4(6): 553-5. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2279562
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CHAPTER 2. NUTRITION AND ANTICOAGULANTS Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and anticoagulants.
Finding Nutrition Studies on Anticoagulants 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 “anticoagulants” (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 is a typical result when searching for recently indexed consumer information on anticoagulants: •
Warfarin. Proper use of this common anticoagulant is important. Source: Anonymous Mayo-Clin-Health-Lett. 2000 May; 18(5): 6 0741-6245
The following information is typical of that found when using the “Full IBIDS Database” to search for “anticoagulants” (or a synonym): •
Acquired coagulopathy due to anticoagulant rodenticide poisoning. Author(s): Division of Clinical Pharmacology, Department of Medicine, Zagreb University Hospital Center and School of Medicine, Kispaticeva 12, Croatia.
[email protected] Source: Huic, M Francetic, I Bakran, I Macolic Sarinic, V Bilusic, M Croat-Med-J. 2002 October; 43(5): 615-7 0353-9504
•
Functional properties of the sex-hormone-binding globulin (SHBG)-like domain of the anticoagulant protein S. Author(s): Unite INSERM 428, Faculte des Sciences Pharmaceutiques et Biologiques, Universite Paris V, Paris, France. Source: Saposnik, B Borgel, D Aiach, M Gandrille, S Eur-J-Biochem. 2003 February; 270(3): 545-55 0014-2956
•
Initiation of oral anticoagulant therapy in orthopedic and surgical patients: an algorithm compared with routine dosing. Author(s): Hospital Pharmacy Midden-Bradbant, TweeSteden Hospital and St. Elisabeth Hopital, P.O. Box 90107, 5000 LA Tilburg, The Netherlands.
[email protected] Source: van den Bemt, P M Beinema, M van Roon, E N Sijtsma, J Baars, W A Mencke, H J Brouwers, J R Eur-J-Clin-Pharmacol. 2002 June; 58(3): 203-208 0031-6970
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PPSB as first choice treatment in the reversal of oral anticoagulant therapy. Author(s):
[email protected] Source: Strengers, P F Drenth, J C Acta-Anaesthesiol-Belg. 2002; 53(3): 183-6 0001-5164
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SSR182289A, a novel, orally active thrombin inhibitor: in vitro profile and ex vivo anticoagulant activity. Author(s): Sanofi-Synthelabo Research, Cardiovascular-Thrombosis Department, ChillyMazarin and Toulouse, France. Source: Berry, C N Lassalle, G Lunven, C Altenburger, J M Guilbert, F Lale, A Herault, J P Lecoffre, C Pfersdorff, C Herbert, J M O'Connor, S E J-Pharmacol-Exp-Ther. 2002 December; 303(3): 1189-98 0022-3565
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Subepicardial aneurysm after anticoagulant therapy for a mural thrombus following anterior myocardial infarction. Author(s): The Heart Institute of Japan, Tokyo Women's Medical University School of Medicine. Source: Niki, K Komiya, N Ishizuka, N Iwade, K Nishikawa, T Nakamura, K Endo, M Kasanuki, H Heart-Vessels. 2002 January; 16(2): 72-4 0910-8327
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Substitution of generic warfarin for Coumadin in an HMO setting. Author(s): Division of General Medical Sciences, Barnes-Jewish Hospital Blood Thinner Clinic, School of Medicine, Washington University, 660 S. Euclid Avenue, St. Louis, MO 63110-1093, USA. Source: Milligan, P E Banet, G A Waterman, A D Gatchel, S K Gage, B F AnnPharmacother. 2002 May; 36(5): 764-8 1060-0280
Nutrition
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The oral anticoagulant saga: past, present, and future. Author(s): Chase Farm Hospital, Enfield, Middlesex, United Kingdom. Source: Duxbury, B M Poller, L Clin-Appl-Thromb-Hemost. 2001 October; 7(4): 269-75 1076-0296
Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •
healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0
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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov
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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov
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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/
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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/
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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/
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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/
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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/
Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html
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Google: http://directory.google.com/Top/Health/Nutrition/
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Healthnotes: http://www.healthnotes.com/
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Open Directory Project: http://dmoz.org/Health/Nutrition/
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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/
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WebMDHealth: http://my.webmd.com/nutrition
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
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The following is a specific Web list relating to anticoagulants; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •
Vitamins Ascorbic Acid Source: Integrative Medicine Communications; www.drkoop.com Vitamin C Source: Prima Communications, Inc.www.personalhealthzone.com Vitamin C (Ascorbic Acid) Source: Integrative Medicine Communications; www.drkoop.com Vitamin E Alternative names: Alpha-Tocopherol, Beta-Tocopherol, D-Alpha-Tocopherol, Delta-Tocopherol, Gamma-Tocopherol Source: Integrative Medicine Communications; www.drkoop.com Vitamin E Source: Prima Communications, Inc.www.personalhealthzone.com Vitamin E Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,906,00.html Vitamin K Alternative names: Menadione, Menaphthone, Menaquinone, Phylloquinone Source: Integrative Medicine Communications; www.drkoop.com Vitamin K Source: Prima Communications, Inc.www.personalhealthzone.com
•
Minerals Alpha-Tocopherol Source: Integrative Medicine Communications; www.drkoop.com Beta-Tocopherol Source: Integrative Medicine Communications; www.drkoop.com Bromelain/Quercetin Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,941,00.html D-Alpha-Tocopherol Source: Integrative Medicine Communications; www.drkoop.com
Nutrition
Delta-Tocopherol Source: Integrative Medicine Communications; www.drkoop.com Gamma-Tocopherol Source: Integrative Medicine Communications; www.drkoop.com Vanadium Alternative names: Vanadate, Vanadyl Source: Integrative Medicine Communications; www.drkoop.com Vinpocetine Source: Prima Communications, Inc.www.personalhealthzone.com •
Food and Diet Chili Peppers Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,132,00.html Garlic Alternative names: Allium sativum Source: Healthnotes, Inc.; www.healthnotes.com Garlic Alternative names: Allium sativum Source: Integrative Medicine Communications; www.drkoop.com Garlic Source: Prima Communications, Inc.www.personalhealthzone.com Garlic Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,786,00.html Mushrooms Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,25,00.html Shiitake Mushrooms Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,308,00.html
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CHAPTER 3. ALTERNATIVE ANTICOAGULANTS
MEDICINE
AND
Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to anticoagulants. At the conclusion of this chapter, we will provide additional sources.
The Combined Health Information Database The Combined Health Information Database (CHID) is a bibliographic database produced by health-related agencies of the U.S. federal government (mostly from the National Institutes of Health) that can offer concise information for a targeted search. The CHID database is updated four times a year at the end of January, April, July, and October. Check the titles, summaries, and availability of CAM-related information by using the “Simple Search” option at the following Web site: http://chid.nih.gov/simple/simple.html. In the drop box at the top, select “Complementary and Alternative Medicine.” Then type “anticoagulants” (or synonyms) in the second search box. We recommend that you select 100 “documents per page” and to check the “whole records” options. The following was extracted using this technique: •
Combining Supplements and Prescription Drugs: What Your Patients Need to Know Source: Alternative and Complementary Therapies. 6(4): 177-183. August 2000. Summary: This journal article reviews what patients need to know about combining herbal supplements and prescription drugs. First, it looks at general clinical issues regarding the concomitant use of herbs and drugs. Then, it summarizes the major concerns, including the lack of knowledge about herbs, lack of quality control for herbal supplements, lack of patient communication about the use of botanicals, and lack of practitioner knowledge about potential interactions. Finally, it reviews known interactions between popular herbal supplements and commonly prescribed classes of drugs, including immunostimulant and immunosuppressive drugs, antidepressants, monoamine oxidase inhibitors, antibiotics, anticoagulants, antihypertensives and diuretics, hypoglycemics and hyperglycemics, and sedatives. The article includes a list
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of herb-drug combinations to avoid, a resources list, a summary of advice for patients, a recommended reading list, and 21 references.
National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov/) has created a link to the National Library of Medicine’s databases to facilitate research for articles that specifically relate to anticoagulants and complementary medicine. To search the database, go to the following Web site: http://www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on PubMed.” Enter “anticoagulants” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of complementary and alternative medicine that are related to anticoagulants: •
Assessment of platelet activation in several different anticoagulants by the Advia 120 Hematology System, fluorescence flow cytometry, and electron microscopy. Author(s): Ahnadi CE, Sabrinah Chapman E, Lepine M, Okrongly D, Pujol-Moix N, Hernandez A, Boughrassa F, Grant AM. Source: Thrombosis and Haemostasis. 2003 November; 90(5): 940-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14597991
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Coagulant and anticoagulant activities in Jatropha curcas latex. Author(s): Osoniyi O, Onajobi F. Source: Journal of Ethnopharmacology. 2003 November; 89(1): 101-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14522439
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Comparison of effects of different anticoagulants and sample handling procedures on rat insulin radioimmunoassay. Author(s): Iglesias R, Villarroya F, Alemany M. Source: Comp Biochem Physiol A. 1985; 82(4): 863-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14575037
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Dietary vitamin K influences intra-individual variability in anticoagulant response to warfarin. Author(s): Khan T, Wynne H, Wood P, Torrance A, Hankey C, Avery P, Kesteven P, Kamali F. Source: British Journal of Haematology. 2004 February; 124(3): 348-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14717783
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EDTA is a better anticoagulant than heparin or citrate for delayed blood processing for plasma DNA analysis. Author(s): Lam NY, Rainer TH, Chiu RW, Lo YM. Source: Clinical Chemistry. 2004 January; 50(1): 256-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14709670
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Effect of anticoagulants and sampling time on results of progesterone determination in canine blood samples. Author(s): Thuroczy J, Wolfling A, Tibold A, Balogh L, Janoki GA, Solti L. Source: Reproduction in Domestic Animals = Zuchthygiene. 2003 October; 38(5): 386-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12950690
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Effect of venipuncture site and anticoagulant on selected hematologic values in black rhinoceros (Diceros bicornis). Author(s): Miller M. Source: J Zoo Wildl Med. 2003 March; 34(1): 59-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12723801
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Effects of anticoagulant from Spirodela polyrhiza in rats. Author(s): Cho HR, Choi HS. Source: Bioscience, Biotechnology, and Biochemistry. 2003 April; 67(4): 881-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12784632
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Influence of anticoagulants on the measurement of S100B protein in blood. Author(s): Tort AB, Dietrich MO, Goncalves CA, Souza DO, Portela LV. Source: Clinical Biochemistry. 2003 November; 36(8): 629-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14636878
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Influence of anticoagulants on the measurement of S100B protein in blood. Author(s): Tort AB, Dietrich MO, Goncalves CA, Souza DO, Portela LV. Source: Clinical Biochemistry. 2003 October; 36(7): 519-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14563444
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Investigation of EDTA anticoagulant in plasma to improve the throughput of liquid chromatography/tandem mass spectrometric assays. Author(s): Sadagopan NP, Li W, Cook JA, Galvan B, Weller DL, Fountain ST, Cohen LH. Source: Rapid Communications in Mass Spectrometry : Rcm. 2003; 17(10): 1065-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12720287
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Marine pharmacology in 2000: marine compounds with antibacterial, anticoagulant, antifungal, anti-inflammatory, antimalarial, antiplatelet, antituberculosis, and antiviral activities; affecting the cardiovascular, immune, and nervous systems and other miscellaneous mechanisms of action. Author(s): Mayer AM, Hamann MT. Source: Marine Biotechnology (New York, N.Y.). 2004 January-February; 6(1): 37-52. Epub 2003 November 03. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14583811
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The effects of different anticoagulants on routine canine plasma biochemistry. Author(s): Ceron JJ, Martinez-Subiela S, Hennemann C, Tecles F. Source: Veterinary Journal (London, England : 1997). 2004 May; 167(3): 294-301. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15080879
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Thrombomodulin allosterically modulates the activity of the anticoagulant thrombin. Author(s): Rezaie AR, Yang L. Source: Proceedings of the National Academy of Sciences of the United States of America. 2003 October 14; 100(21): 12051-6. Epub 2003 Oct 01. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14523228
Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •
Alternative Medicine Foundation, Inc.: http://www.herbmed.org/
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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats
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Chinese Medicine: http://www.newcenturynutrition.com/
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drkoop.com: http://www.drkoop.com/InteractiveMedicine/IndexC.html
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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm
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Google: http://directory.google.com/Top/Health/Alternative/
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Healthnotes: http://www.healthnotes.com/
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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine
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Open Directory Project: http://dmoz.org/Health/Alternative/
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HealthGate: http://www.tnp.com/
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WebMDHealth: http://my.webmd.com/drugs_and_herbs
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/
The following is a specific Web list relating to anticoagulants; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •
General Overview Anemia Source: Integrative Medicine Communications; www.drkoop.com
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Atherosclerosis and Heart Disease Prevention Source: Prima Communications, Inc.www.personalhealthzone.com Bruising Source: Healthnotes, Inc.; www.healthnotes.com Cancer Prevention (Reducing the Risk) Source: Prima Communications, Inc.www.personalhealthzone.com Capillary Fragility Source: Healthnotes, Inc.; www.healthnotes.com Cataracts (prevention) Source: Prima Communications, Inc.www.personalhealthzone.com Cyclic Mastalgia Alternative names: Cyclic Mastitis, Fibrocystic Breast Disease Source: Prima Communications, Inc.www.personalhealthzone.com Dementia Source: Integrative Medicine Communications; www.drkoop.com Depression (Mild to Moderate) Source: Prima Communications, Inc.www.personalhealthzone.com Dysmenorrhea Alternative names: Painful Menstruation Source: Prima Communications, Inc.www.personalhealthzone.com Eczema Source: Prima Communications, Inc.www.personalhealthzone.com Edema Source: Healthnotes, Inc.; www.healthnotes.com Fainting Source: Integrative Medicine Communications; www.drkoop.com Heart Attack Source: Healthnotes, Inc.; www.healthnotes.com High Cholesterol Source: Prima Communications, Inc.www.personalhealthzone.com Hypertension Alternative names: High Blood Pressure Source: Prima Communications, Inc.www.personalhealthzone.com Macular Degeneration Source: Integrative Medicine Communications; www.drkoop.com
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Migraine Headaches Source: Prima Communications, Inc.www.personalhealthzone.com Nausea Source: Prima Communications, Inc.www.personalhealthzone.com Osteoporosis Source: Prima Communications, Inc.www.personalhealthzone.com Prostate Cancer Source: Healthnotes, Inc.; www.healthnotes.com Psoriasis Source: Prima Communications, Inc.www.personalhealthzone.com Pulmonary Hypertension Source: Integrative Medicine Communications; www.drkoop.com Rheumatoid Arthritis Source: Prima Communications, Inc.www.personalhealthzone.com Senile Dementia Source: Integrative Medicine Communications; www.drkoop.com Stroke Source: Healthnotes, Inc.; www.healthnotes.com Stroke Source: Integrative Medicine Communications; www.drkoop.com Syncope Source: Integrative Medicine Communications; www.drkoop.com TIAs Source: Integrative Medicine Communications; www.drkoop.com Transient Ischemic Attacks Source: Integrative Medicine Communications; www.drkoop.com Varicose Veins Source: Prima Communications, Inc.www.personalhealthzone.com •
Alternative Therapy Acupuncture Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,663,00.html Aston-Patterning Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com
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Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10118,00.html •
Herbs and Supplements Acorus Alternative names: Sweet Flag; Acorus calamus L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Aesculus Alternative names: Horse Chestnut; Aesculus hippocastanum L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Allium Sativum Alternative names: Garlic Source: Integrative Medicine Communications; www.drkoop.com Antioxidants Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10004,00.html Aortic Glycosaminoglycans Source: Prima Communications, Inc.www.personalhealthzone.com Aspirin Source: Healthnotes, Inc.; www.healthnotes.com Bromelain Source: Prima Communications, Inc.www.personalhealthzone.com Bromelain Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,760,00.html Chamomile Source: Prima Communications, Inc.www.personalhealthzone.com Coleus Forskohlii Source: Prima Communications, Inc.www.personalhealthzone.com Devil's Claw Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,970,00.html Dipyridamole Source: Healthnotes, Inc.; www.healthnotes.com Dong Quai (Angelica) Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com
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Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,774,00.html Feverfew Source: Prima Communications, Inc.www.personalhealthzone.com Feverfew Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,780,00.html Ginger Alternative names: Zingiber officinale Source: Integrative Medicine Communications; www.drkoop.com Ginger Source: Prima Communications, Inc.www.personalhealthzone.com Ginkgo Source: Prima Communications, Inc.www.personalhealthzone.com Ginkgo Biloba Alternative names: Maidenhair Tree Source: Integrative Medicine Communications; www.drkoop.com Ginkgo Biloba Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,788,00.html Ginseng Source: Prima Communications, Inc.www.personalhealthzone.com Grape Seed Extract Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,793,00.html Green Tea Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10032,00.html Heparin Source: Healthnotes, Inc.; www.healthnotes.com Heparin Alternative names: Hep-Lock Source: Prima Communications, Inc.www.personalhealthzone.com Horse Chestnut Source: Prima Communications, Inc.www.personalhealthzone.com
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Horse Chestnut Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10037,00.html Hypericum Perforatum Alternative names: St. John's Wort Source: Integrative Medicine Communications; www.drkoop.com Ipriflavone Source: Prima Communications, Inc.www.personalhealthzone.com Klamathweed Alternative names: St. John's Wort Source: Integrative Medicine Communications; www.drkoop.com Maidenhair Tree Alternative names: Ginkgo Biloba Source: Integrative Medicine Communications; www.drkoop.com Menadione Source: Integrative Medicine Communications; www.drkoop.com Menaphthone Source: Integrative Medicine Communications; www.drkoop.com Menaquinone Source: Integrative Medicine Communications; www.drkoop.com MSM Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,807,00.html Nettle Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10048,00.html OPCS (Oligomeric Proanthocyanidins) Source: Prima Communications, Inc.www.personalhealthzone.com Pau d'Arco Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,811,00.html Phosphatidylserine Source: Prima Communications, Inc.www.personalhealthzone.com
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Phylloquinone Source: Integrative Medicine Communications; www.drkoop.com Red Clover Source: Prima Communications, Inc.www.personalhealthzone.com Reishi Source: Prima Communications, Inc.www.personalhealthzone.com St. John's Wort Alternative names: Hypericum perforatum Source: Integrative Medicine Communications; www.drkoop.com Ticlopidine Source: Healthnotes, Inc.; www.healthnotes.com Vanadate Source: Integrative Medicine Communications; www.drkoop.com Vanadyl Source: Integrative Medicine Communications; www.drkoop.com Warfarin Source: Healthnotes, Inc.; www.healthnotes.com Warfarin Alternative names: Coumadin Source: Prima Communications, Inc.www.personalhealthzone.com Willow Bark Source: Integrative Medicine Communications; www.drkoop.com Zingiber Officinale Source: Integrative Medicine Communications; www.drkoop.com
General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.
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CHAPTER 4. DISSERTATIONS ON ANTICOAGULANTS Overview In this chapter, we will give you a bibliography on recent dissertations relating to anticoagulants. We will also provide you with information on how to use the Internet to stay current on dissertations. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “anticoagulants” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on anticoagulants, we have not necessarily excluded non-medical dissertations in this bibliography.
Dissertations on Anticoagulants ProQuest Digital Dissertations, the largest archive of academic dissertations available, is located at the following Web address: http://wwwlib.umi.com/dissertations. From this archive, we have compiled the following list covering dissertations devoted to anticoagulants. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: •
Antagonism between vitamin K1 and coumarin anticoagulants evidence in vitro studies that the anticoagulant effect depends on inhibition of vitamin K uptake by Birnbaum, Henry; ADVDEG from McGill University (Canada), 1970 http://wwwlib.umi.com/dissertations/fullcit/NK07255
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The efficacy of a nurse-directed intervention on the knowledge of individuals receiving Coumadin therapy by Jackson, Deanna Paige; MSN from Texas Tech University, 2003, 63 pages http://wwwlib.umi.com/dissertations/fullcit/1417077
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Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.
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CHAPTER 5. PATENTS ON ANTICOAGULANTS Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.8 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “anticoagulants” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on anticoagulants, we have not necessarily excluded non-medical patents in this bibliography.
Patents on Anticoagulants By performing a patent search focusing on anticoagulants, 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. The following is an 8Adapted from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.
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example of the type of information that you can expect to obtain from a patent search on anticoagulants: •
Anticoagulant compositions Inventor(s): Mickus; James C. (5269 Heritage Hills Dr., Bloomington, MN 55437) Assignee(s): none reported Patent Number: 6,423,348 Date filed: December 15, 1998 Abstract: What is shown is an animal blood anticoagulant compound useful in the meat packing industry generally, and in slaughterhouse operations, particularly. The anticoagulant is effective when diluted with water at higher dilution ratios than earlier anticoagulants. In some field trials, this anticoagulant was at least as effective as previously known commercial anticoagulants when diluted by an additional 30%. The present anticoagulant preparation concentrate is an aqueous mixture of soft water (55.0%-65.0/%, w/w); tetrasodium ethylene diamine tetraacetate (Na.sub.4 EDTA) (0.5%-3.0%, w/w); sodium hexametaphosphate (17.0%-24.0%, w/w); citric acid (5.0%9.0%, w/w); and sodium hydroxide (4.0%-7.0%, w/w) to obtain a balanced pH that provides optimal chelating and anticoagulant activity. Optimal anticoagulant performance has been found to occur in the range of between pH 6.6 and pH 7.2. The degree to which the product may be diluted varies with the characteristics of the facility, the diluent water, the species of animal blood being treated, and the breed of the species, among other things. Excerpt(s): The present invention relates to the field of anticoagulant compositions, generally, and to anticoagulant compounds adapted for use in slaughterhouses, more particularly. A method of making improved anticoagulant compositions is disclosed. In addition, a method of using anticoagulant compositions is described. Most specifically, the present disclosure teaches an improved method by which a selected mixture of chelating agents, or sequestering agents, may be used in a slaughterhouse as an animal blood anticoagulant. Anticoagulant compositions are used in slaughterhouse operations to permit the recovery of blood from the work area. In particular, the area where animals are killed and bled must be cleaned frequently to prevent the rapid accumulation of coagulated blood which could be removed only with great difficulty. Blood from slaughter animals was traditionally viewed as a low value component that is sometimes discarded or used for fertilizer. There is, however, an improving market for various whole blood constituents. Dried animal plasma proteins may be purified and used as a protein additive in many products, including confectionary and other food products for human consumption. In addition, dried animal red blood cells (RBC) are routinely added to dark breads in some European countries. Web site: http://www.delphion.com/details?pn=US06423348__
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Controlling donor blood characteristics Inventor(s): Grode; Gerald A. (Vernon Hills, IL), Stewart; Mary A. (Mundelein, IL) Assignee(s): Baxter International Inc. (Deerfield, IL) Patent Number: 6,277,556 Date filed: December 17, 1998
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Abstract: A new citrate-based anticoagulant for donor whole blood provides good platelet yield and cell morphology at a significantly reduced risk of donor paresthesia during apheresis procedures. The primary citrate anticoagulant compositions include a citric acid to total citrate ratio greater than about 30%. The anticoagulants are mixed with whole blood to provide an anticoagulated blood mixture which contains a citric acid concentration of greater than about 5.0 mM, a total citrate concentration of less than about 20 mM, and an initial blood pH of less than about 6.75. The platelet rich products including PRP and PC prepared from blood collected in accordance with the invention exhibit better platelet yields and better platelet morphology on storage. Excerpt(s): The present invention generally relates to blood collection procedures and blood component separation methods. More particularly, it relates to new and improved methods of collecting blood into anticoagulant formulations designed to promote increased platelet yield and improved overall platelet morphology in platelet collection procedures. Today there exists a number of automated donor hemopheresis systems for separation of blood, including whole blood into components or fractions. The systems are designed to collect one or more components, such as plasma, white cells, platelets and red cells, for further use or for disposal; to return certain components to the donor, who may be a patient; and/or to treat a component, for subsequent return to a donor. One such system is the Autopheresis-C.RTM. systems sold by Baxter Healthcare Corporation of Deerfield, Illinois, a wholly-owned subsidiary of the assignee of the present invention. That system utilizes a microprocessor-controlled instrument including automated processing programs, in conjunction with a disposable set. The Autopheresis-C.RTM. device may, when disposable plasmapheresis set is installed therein, be used to collect plasma from whole blood drawn from a donor. A rotating membrane in a separation chamber of the disposable may in fact be wetted by an anticoagulant priming operation before blood is withdrawn from the donor, as shown in U.S. patent application Ser. No. 07/106,089, filed Oct. 7, 1987, entitled "Method for Wetting a Plasmapheresis Filter with Anticoagulant" and the corresponding PCT International Application Publication No. WO89/03229. Web site: http://www.delphion.com/details?pn=US06277556__ •
Method for inducing therapeutically-effective proteins Inventor(s): Meijer; Hans (Koln, DE), Reincke; Julio (Koln, DE), Wehling; Peter (Dusseldorf, DE) Assignee(s): Orthogen Gentechnologic. GmbH (Dusseldorf, DE) Patent Number: 6,623,472 Date filed: July 6, 2000 Abstract: A method for inducing therapeutically-effective protein includes selecting a syringe having inner structures coated with an inductor, disposing a therapeuticallyeffective protein therein with a body fluid and incubating the syringe and its contents. The inductor can be coated onto the interior of the syringe itself or can be placed on other structures and inserted into the interior of the syringe. A variety of inductors and body fluids may be used. Anticoagulants may also be used. Excerpt(s): This invention relates to a method for producing therapeutically-effective proteins as well as the means used therein, in particular syringes. Therapeuticallyeffective proteins, such as erythropoietin, insulin or interferon, have been known for a long time. Many of these proteins are already registered drugs and accordingly are
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commonly used. Because of the high cost connected with the development and registration of these medications, there is however a need for simple and inexpensive alternatives for the preparation of therapeutically-effective proteins. In addition, not all therapeutically-effective proteins are registered drugs. However, there nevertheless frequently is the requirement to administer these proteins as well as patients. Of particular importance in this context are autologous, that is intrinsic, body proteins because of their presumed good bodily tolerance. Among these proteins are interleukin 1 receptor antagonist, interleukin-4, interleukin-10 and tumour necrosis factor receptor Type I or Type II. The stimulation of monocytes by adherent immunoglobulin G for the formation of interleukin 1 receptor antagonists is described by Arend and Leung in Immunological Reviews (1994) 139, 71-78 and Moore et al. in Am. J. Respir. Cell Mol. Biol. (1992) 6, 569-575. Andersen et al., in Autoimmunity (1995) 22, 127-33, explained that the therapeutic effect of immunoglobulin G to be observed in vivo cannot be put down to an intensified formation of interleukin 1 receptor antagonist, and that the in vitro formation of interleukin 1 receptor antagonist (IRAP, IL-Ira) occurs by means of monocytes in dependence on serum and plasma components absorbed in polypropylene. Methods of producing IL-Ira directly usable in therapy are not described in these publications. Web site: http://www.delphion.com/details?pn=US06623472__ •
Method of evaluating blood clot lysis condition Inventor(s): Baugh; Robert F. (7926 Windcrest Row, Parker, CO 80134) Assignee(s): none reported Patent Number: 6,472,161 Date filed: January 11, 1996 Abstract: Blood is tested for clot lysis conditions such as natural lytic capabilities, the effect of previously administered thrombolytic and anti-thrombolytic agents, and dose responses thereto, by forming a clot in a sample of blood, lysing the clot, and measuring the elapsed time period from initial clot formation to clot lysis, all while continuously evaluating the blood sample. Thrombolytic agents include streptokinase, urokinase and recombinant tissue plasminogen activator. Plasmin and plasminogen activator inhibitors, clot activating agents (e.g. kaolin), and agents to deactivate anticoagulants (e.g. heparinase) may also be used as reagents during testing. Excerpt(s): This invention relates to a technique for determining and measuring clotting related conditions in blood. More particularly, this invention relates to a new and improved technique for determining blood clot lysis conditions. In addition the present invention pertains to determining blood clot lysis times quickly and consistently with a high degree of sensitivity, to detecting thrombolysis or pathological fibrinolysis, to measuring the effect of therapeutically administered thrombolytic and anti-fibrinolytic agents, and to developing dose response information for the therapeutic administration of thrombolytic and anti-fibrinolytic agents, among other things. Fibrinolysis is the process in which blood clots are dissolved. Fibrinolysis is the final step in the natural reparative process which follows blood clot formation, as when a blood clot which was previously formed in response to blood vessel damage is subsequently dissolved after the damage has been repaired. Fibrinolysis may also be induced by the therapeutic administration of thrombolytic agents. Thrombolytic agents are administered to avoid the complications of pulmonary embolism resulting from lower limb venous thrombosis and to minimize the cell destruction of myocardial infarctions, gangrene and stroke
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caused by arterial thrombosis, among other reasons. Whether or not cell destruction can be minimized after physiological events such as myocardial infarctions, stroke or gangrene may depend, in part, upon the existence of pathological or therapeutically induced thrombolysis. In order to eliminate or minimize such cell destruction in an individual who has undergone or is undergoing a stroke, heart attack or similar event, it would be helpful to ascertain quickly whether the individual's clot lysis ability is within a normal range of lytic response times. By comparing the individual's specific lytic response time to the average lytic response time of a normal, non-pathogenic individual, a treating physician could determine whether the patient's specific lytic response capability needs to be treated or otherwise taken into consideration. Web site: http://www.delphion.com/details?pn=US06472161__ •
Thrombin inhibitors Inventor(s): Baucke; Dorit (Mannheim, DE), Hoffken; Hans Wolfgang (Ludwigshafen, DE), Hornberger; Wilfried (Neustadt, DE), Lange; Udo (Ludwigshafen, DE), Mack; Helmut (Ludwigshafen, DE), Seitz; Werner (Plankstadt, DE) Assignee(s): Abbott GmbH & Co., KG (Wiesbaden, DE) Patent Number: 6,740,647 Date filed: June 21, 2000 Abstract: Novel five-membered heterocyclic amidines, their preparation and use as competitive inhibitors of trypsin-like serine proteases, especially thrombin and kininogenases such as kallikrein. Pharmaceutical compositions which contain the compounds as active ingredients, and use of the compounds as thrombin inhibitors, anticoagulants and antiinflammatory agents. Excerpt(s): The present invention relates to novel five-membered heterocyclic amidines, to their preparation and to their use as competitive inhibitors of trypsin-like serine proteases, especially thrombin and kininogenases such as kallikrein. The invention also relates to pharmaceutical compositions which contain the compounds as active ingredients, and to the use of the compounds as thrombin inhibitors, anticoagulants and antiinflammatory agents. Thrombin belongs to the group of serine proteases and plays a central part in the blood coagulation cascade as terminal enzyme. Both the intrinsic and the extrinsic coagulation cascade lead via a plurality of amplifying stages to the production of thrombin from prothrombin. Thrombin-catalyzed cleavage of fibrinogen to fibrin then initiates blood coagulation and aggregation of platelets which, in turn, due to the binding of platelet factor 3 and coagulation factor XIII, and a large number of highly active mediators, enhance thrombin formation. The formation and action of thrombin are central events in the development both of white, arterial and of red, venous thrombi and are therefore potentially effective points of attack for drugs. Thrombin inhibitors are, by contrast with heparin, able independently of cofactors completely to inhibit simultaneously the effects of free thrombin and of that bound to platelets. They are able to prevent in the acute phase thromboembolic events after percutaneous transluminal coronary angioplasty (PTCA) and lysis, and to act as anticoagulants in extracorporeal circulation (heart-lung machine, hemodialysis). They can also be used generally for the prophylaxis of thrombosis, for example after surgical operations. Web site: http://www.delphion.com/details?pn=US06740647__
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Use of citrate-containing dialysate for renal dialysis treatment Inventor(s): Warnock; David G. (Birmingham, AL) Assignee(s): UAB Research Foundation (Birmingham, AL) Patent Number: 6,566,402 Date filed: May 23, 2001 Abstract: The present invention describes trisodium citrate-containing dialysates and production thereof. Also described are the applications of such dialysates as regional anticoagulants during hemodialysis and all modes of continuous renal replacement therapy which utilize any form of dialysis. Excerpt(s): The present invention relates generally to the field of medical therapy of renal disease. More specifically, the present invention relates to the use of trisodium citrate-containing dialysate solutions during hemodialysis and continuous renal replacement therapy, wherein trisodium citrate functions as a regional anticoagulant. Continuous arteriovenous hemodialysis (CAVHD) and other forms of continuous renal replacement therapy (CRRT) are being used increasingly as the major form of renal replacement therapy for critically ill patients with acute renal failure (ARF). Generally, the procedure has required systemic anticoagulation utilizing heparin or, in a few cases, prostacyclin to maintain filter patency. Although heparin is removed by continuous arteriovenous hemodialysis membranes, systemic anticoagulation is usually unavoidable with heparin and has been associated with an increased incidence of bleeding. In order to circumvent this problem, regional heparin anticoagulation has been tried, but this has not gained widespread acceptance due to the difficulty in accurately adjusting protamine doses. Similarly, continuous arteriovenous hemodialysis has been attempted with frequent saline flushes through the filter, but it has been difficult to keep the filter patent for longer than 24 hours. U.S. Pat. No. 5,032,615 describes a technique employing sodium citrate as a regional anticoagulant for continuous arteriovenous hemodialysis (citrate CAVHD) which results in removal of excess water, electrolytes and catabolic toxins without requiring systemic anticoagulation. Citrate is infused at the origin of the extracorporeal circuit, and the citrate-calcium chelate is removed by diffusion across the membrane. The metabolic consequences of the sodium citrate load are compensated for by the use of a special dialysate containing no alkali, subnormal sodium concentration, and no calcium. Calcium homeostasis is restored by a peripheral infusion of calcium chloride into the patient. Web site: http://www.delphion.com/details?pn=US06566402__
Patent Applications on Anticoagulants As of December 2000, U.S. patent applications are open to public viewing.9 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to anticoagulants:
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This has been a common practice outside the United States prior to December 2000.
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Amidino derivatives, and anticoagulants and thrombosis therapeutic agents containing them Inventor(s): Asano, Osamu; (Ushiku-shi, JP), Inoue, Atsushi; (Tsukuba-shi, JP), Nagakura, Tadashi; (Ushiku-shi, JP), Okamoto, Yasushi; (Tsukuba-gun, JP), Saeki, Takao; (Moriya-shi, JP), Sakurai, Masahiro; (Tsukuba-shi, JP), Satoh, Takashi; (Tsukubashi, JP), Watanabe, Nobuhisa; (Tsukuba-shi, JP) Correspondence: Knobbe Martens Olson & Bear Llp; 2040 Main Street; Fourteenth Floor; Irvine; CA; 92614; US Patent Application Number: 20030181766 Date filed: November 14, 2002 Abstract: Amidino derivatives represented by the following general formula (I): 1{where X is a group represented by R.sup.1SO.sub.2NR.sup.2-- (wherein R.sup.1 represents optionally substituted C.sub.6-14 aryl, etc. and R.sup.2 represents hydrogen atom, etc.), etc., Ar.sup.1 represents 2,6-naphthylene, etc., R.sup.3 represents hydrogen atom, etc. and Y represents carboxyphenyl, etc.}and their pharmacologically acceptable salts or solvates. Excerpt(s): The present invention relates to medicinally useful novel amidino derivatives, to their pharmacologically acceptable salts or solvates, and to blood clotting factor VIIa inhibitors, anticoagulants and thrombosis therapeutic agents containing them as active ingredients. Destruction of blood vessels in the body triggers rapid production of thrombin to prevent death by bleeding. On the other hand, overproduction of thrombin accompanying inflammation reaction at damaged-blood vessels leads to thrombosis, which impairs the functioning of important organs. Thrombin inhibitors such as heparin and warfarin, which inhibit thrombin production or directly inhibit thrombin activity, have long been used as anticoagulants for treatment or prevention of thrombosis. However, because such drugs have not been very satisfying from a therapeutic standpoint, research and development have been pursued on a worldwide scale for new anticoagulants with excellent dose response, low risk of hemorrhage and suitability for oral administration. Incidentally, mechanisms of blood clotting had been divided into two types, of the "intrinsic coagulation pathway" which is initiated by activation of Factor XII (FXII) by contact with negatively charged substances, or of the "extrinsic coagulation pathway" which is activated by Tissue Factor (TF) and Factor VII (FVII). It is extrinsic coagulation that is implicated in thrombosis because of specific expression of TF observed in the clinical condition. In the blood clotting cascade, compounds that inhibit blood clotting factor VIIa, which is furthest upstream in the extrinsic coagulation pathway, are believed to be useful as prophylactic and/or therapeutic agents for clinical conditions involving thrombogenesis in which extrinsic clotting mechanisms are implicated. In addition, blood clotting factor VIIa inhibitors, unlike thrombin inhibitors, are expected to produce milder hemorrhage since the intrinsic coagulation pathway still remains, and are thus believed to be useful from this viewpoint as well. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Aminoheterocyclic derivatives as antithrombotic or anticoagulant agents Inventor(s): Preston, John; (Cheshire, GB), Smithers, Michael James; (Cheshire, GB), Stocker, Andrew; (Cheshire, GB) Correspondence: Morgan Lewis & Bockius Llp; 1111 Pennsylvania Avenue NW; Washington; DC; 20004; US Patent Application Number: 20030207882 Date filed: May 2, 2003 Abstract: Compounds of formula (I), wherein G.sup.1 is CH or N; G.sup.2 is CH or N; R.sup.1 is a variety of optional substituents, L.sup.1 is (1-4C)alkylene; T.sup.1 is CH or N; R.sup.2 and R.sup.3 are independently hydrogen or (1-4C)alkyl or are joined to form a ring; X.sup.1 and X.sup.2 represent various linking groups; Ar is phenylene or certain heteroaryl rings and Q represents a variety of aromatic or heterocyclic rings systems, and pharmaceutically acceptable salts thereof are described as useful antithrombotic and anticoagulant agents, and are selective Factor Xa inhibitors. Processes for their preparation and pharmaceutical compositions containing them are also described. 1 Excerpt(s): The invention relates to aminoheterocyclic derivatives and pharmaceuticallyacceptable salts thereof, which possess antithrombotic and anticoagulant properties and are accordingly useful in methods of treatment of the human or animal body. The invention also relates to processes for the preparation of said aminoheterocyclic derivatives, to pharmaceutical compositions containing them and to their use in the manufacture of medicaments for use in the production of an antithrombotic or anticoagulant effect. The antithrombotic and anticoagulant effect produced by the compounds of the invention is believed to be attributable to their strong inhibitory effect against the activated coagulation protease known as Factor Xa. Factor Xa is one of a cascade of proteases involved in the complex process of blood coagulation. The protease known as thrombin is the final protease in the cascade and Factor Xa is the preceding protease which cleaves prothrombin to generate thrombin. Certain compounds are known to possess Factor Xa inhibitory properties and the field has been reviewed by R. B. Wallis, Current Opinion in Therapeutic Patents, 1993, 1173-1179. Thus it is known that two proteins, one known as antistasin and the other known as tick anticoagulant protein (TAP), are specific Factor Xa inhibitors which possess antithrombotic properties in various animal models of thrombotic disease. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Anti-tissue factor antibodies with enhanced anticoagulant potency Inventor(s): Kirchhofer, Daniel K.; (Los Altos, CA), Lowe, David G.; (Hillsborough, CA), Presta, Leonard G.; (San Francisco, CA) Correspondence: Genentech, INC.; 1 Dna Way; South San Francisco; CA; 94080; US Patent Application Number: 20030119075 Date filed: March 8, 2001 Abstract: The invention concerns anti-tissue factor (anti-TF) antibodies with enhanced anticoagulant potency, and methods and means for identifying, producing and using such antibodies. The anti-TF antibodies of the present invention are designed to comprise a region binding to an epitope in the C-terminal macromolecular substrate binding region of TF.
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Excerpt(s): This application is a non-provisional application filed under 37 CFR 1.53(b)(1), claiming priority under 35 USC 119(e) to provisional application No. 60/189,775 filed Mar. 16, 2000, the contents of which are incorporated herein by reference. This invention concerns methods for engineering anti-tissue factor (anti-TF) antibodies, especially those having enhanced anticoagulant potency. The invention further concerns anti-TF antibodies, methods and means for producing them, compositions comprising the antibodies and their use in the diagnosis, management, prevention and treatment of various diseases and disorders. Tissue factor (TF) is the receptor for coagulation factor VIIa (FVIIa) and the zymogen precursor factor VII (FVII). Native human TF (hTF) is a 263 amino acid residue glycoprotein composed of an extracellular domain (residues 1 to 219), a single transmembrane domain (residues 220242), and a short cytoplasmic domain (residues 243 to 263) (Fisher et al., [1987] Thromb. Res. 48:89-99, Morrissey et al., [1987] Cell 50:129-135). The TF extracellular domain is composed of two immunoglobulin-like fibronectin type III domains of about 105 amino acids each (Huang et al., [1998] J. Mol. Biol. 275:873-894). Each domain is formed by two anti-parallel.beta.-sheets with Ig superfamily type C2 homology. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Apheresis system with anticoagulant flow control Inventor(s): Grimm, Daniel J.; (McHenry, IL) Correspondence: Bradford R. L. Price, Esquire; Baxter Healthcare Corporation; Fenwal Division, Rlp-30; RT. 120 And Wilson Road, P.O. Box 490; Round Lake; IL; 60073; US Patent Application Number: 20030175150 Date filed: February 24, 2003 Abstract: An apheresis system is disclosed which may include a separation chamber; a suspension flow path which communicates at one end with the separation chamber and includes a connector at the other end for connecting to a source of cellular suspension; an anticoagulant flow path which communicates at one end with the suspension flow path and includes a connector at the other end for connecting to an anticoagulant source; and a return flow path which communicates at one end with the separation chamber and communicates at the other end with a connector for connection directly to the suspension source or to the suspension flow path for returning one or more suspension components to the source. The anticoagulant flow path includes a flow restriction, such as an internal flow restriction, which limits the free flow of anticoagulants into the suspension flow path while preferably not completely stopping the flow of anticoagulant. The restriction may take various forms, but the preferred construction comprises a tubing segment of reduced inside diameter, providing resistance to the free flow of anticoagulant in the event of operator error or mechanical failure. Excerpt(s): The present invention generally relates to apheresis systems for separating one or more components from a cellular suspension such as blood. More specifically, the present invention relates to an improved apheresis system that limits the free flow of anticoagulant in the event of improper assembly or mechanical failure of the apheresis system. The separation of blood into one or more component parts, such as platelets, red cells or plasma, has been well known for many years. Within the past twenty years, automated apheresis systems, which automatically process the blood of a donor or patient, separate out the desired blood component and return the remainder to the donor/patient, have become commonplace in developed countries. Typically such
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automated apheresis systems employ a fluid circuit assembly, for example, a preassembled disposable plastic tubing and container set, which is mounted on a reusable hardware device. The reusable hardware device includes pumps, monitors, drive systems and the like for carrying out, in combination with the disposable fluid circuit assembly or system, a blood apheresis procedure. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Assays for determining anticoagulant cofactor activity Inventor(s): Dahlback, Bjorn; (Malmo, SE) Correspondence: Testa, Hurwitz & Thibeault, Llp; High Street Tower; 125 High Street; Boston; MA; 02110; US Patent Application Number: 20030143759 Date filed: July 25, 2001 Abstract: Methods are disclosed for determining, in a sample derived from a human, the functional activity of a component of the human blood coagulation system, which activity can be correlated to conversion of a substrate specific for activated Protein C (APC), by measuring in an assay medium containing the sample and a substrate for APC, the conversion of the substrate by APC and correlating the conversion to the functional activity of the component. When the component is anticoagulant Factor V, at least one of exogenous APC, Protein S or an inhibitor of Protein S activity is added to the medium. When the component is Protein C, APC, or Protein S, exogenous anticoagulant Factor V or an inhibitor of anticoagulant activity of Factor V is added to the medium. Methods are also disclosed for diagnosing a blood coagulation/anticoagulation disorder or for determining a predisposition thereto in a human by determining anticoagulant Factor V activity in an assay medium containing a sample derived from the human. Excerpt(s): The present invention is generally related to a novel anticoagulant cofactor activity involved in the human blood coagulation system and possibly also involved in the blood coagulation system of some other mammal species. Blood coagulation is a complex system involving a large number of proteins that function in concert with platelets to yield hemostasis. The coagulation system is strictly regulated by a series of anticoagulant proteins present in plasma and on the surface of endothelial blood cells (Esmon, J. Biol. Chem. 264 (1989) 4743-4746; Bauer, Sem. Hematol. 28 (1991) 10-18; and Rapaport, Blood 73 (1989) 359-65). Under physiological conditions, pro- and anticoagulant mechanisms are delicately balanced to provide hemostasis and coagulation. Disturbances in this balance result in either bleeding or thromboembolic disorders. In the above mentioned anticoagulant system, Protein C, a vitamin K-dependent plasma protein, is a key component that after activation to Activated Protein C (APC) on endothelial cells by the thrombin/thrombomodulin complex selectively degrades the coagulation Factors V.sub.a and VIII.sub.a, i e the activated forms of the coagulation Factor V and VIII, respectively. (Esmon, loc. cit.; Stenflo, in Protein C and related proteins, ed. Bertina (Churchill Livingstone Longham Group, UK) (1988) 21-54; Mann et al., Ann. Rev. Biochem. 57 (1988) 915-956; and Kane et al., Blood 71 (1988) 539-55). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Barrier device for ostium of left atrial appendage Inventor(s): Hauser, Robert G.; (Long Lake, MN), Van Tassel, Robert A.; (Excelsior, MN) Correspondence: Fish & Neave; 1251 Avenue OF The Americas; 50th Floor; New York; NY; 10020-1105; US Patent Application Number: 20030120337 Date filed: December 3, 2002 Abstract: A membrane applied to the ostium of an atrial appendage for blocking blood from entering the atrial appendage which can form blood clots therein is disclosed. The membrane also prevents blood clots in the atrial appendage from escaping therefrom and entering the blood stream which can result in a blocked blood vessel, leading to strokes and heart attacks. The membranes are percutaneously installed in patients experiencing atrial fibrillations and other heart conditions where thrombosis may form in the atrial appendages. A variety of means for securing the membranes in place are disclosed. The membranes may be held in place over the ostium of the atrial appendage or fill the inside of the atrial appendage. The means for holding the membranes in place over the ostium of the atrial appendages include prongs, stents, anchors with tethers or springs, disks with tethers or springs, umbrellas, spiral springs filling the atrial appendages, and adhesives. After the membrane is in place a filler substance may be added inside the atrial appendage to reduce the volume, help seal the membrane against the ostium or clot the blood in the atrial appendage. The membranes may have anticoagulants to help prevent thrombosis. The membranes be porous such that endothelial cells cover the membrane presenting a living membrane wall to prevent thrombosis. The membranes may have means to center the membranes over the ostium. Sensors may be attached to the membrane to provide information about the patient. Excerpt(s): The invention relates to a membrane or plug structure applied to the ostium of an atrial appendage for preventing blood flow and physical connection between an atrium of the heart and the associated atrial appendage or appendages to isolate an atrial appendage and prevent thrombus leaving therefrom. There are a number of heart diseases (e.g. coronary artery disease, mitral valve disease) that have various adverse effects on the heart. An adverse effect of certain cardiac diseases, such as mitral valve disease, is atrial (or auricular) fibrillation. Atrial fibrillation may result in pooling of blood in the left atrial appendage. Blood pooling may also be spontaneous. When blood pools in the atrial appendage, blood clots can form and accumulate therein, build upon themselves, and propagate out from the atrial appendage into the atrium. These blood clots can then enter the systemic or pulmonary circulations and cause serious problems if they migrate from the atrial appendage and become free in the blood stream and embolize distally into the arterial system. Similar problems also occur when a blood clot extending from an atrial appendage into an atrium breaks off and enters the blood supply. Since blood from the left atrium and ventricle supply the heart and brain, blood clots from the atrial appendages can obstruct blood flow therein causing heart attacks, strokes or other organ ischemia. It is therefore necessary to find a means of preventing blood clots from forming in the atrial appendages and to prevent these blood clots, once formed, from leaving the atrial appendages to the heart, lungs, brain or other circulations of the patient which can cause heart attacks or strokes or other organ ischemia. U.S. Pat. No. 5,865,791 relates to the reduction of regions of blood stasis and ultimately thrombus formation in such regions, particularly in the atrial appendages of patients with atrial fibrillation. More specifically, the invention relates to procedures and devices for affixing the atrial appendages in an orientation that prevents subsequent formation of thrombus. The invention removes the appendage from the atrium by
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pulling on it and putting a loop around it to form a sack of the atrial appendage and then cut off from the rest of the heart. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Clotting cascade initiating apparatus and methods of use and methods of closing wounds Inventor(s): Nowakowski, Karol L.; (Circle Pines, MN) Correspondence: Robert C. Freed; Moore & Hansen; 2900 Wells Fargo Center; 90 South Seventh Street; Minneapolis; MN; 55402; US Patent Application Number: 20030093116 Date filed: November 8, 2002 Abstract: Wound closure methods and apparatus are provided which utilize blood fluid by activating the clotting cascade of the blood fluid outside the body within a substantially enclosed sterile container then introducing the blood fluid to the wound site to complete clotting. Methods and apparatus for providing ways of inhibiting anticoagulants and slowing fibrin clot degradation are also disclosed. Kits for practicing the invention singularly or in combination with and/or associated with preferred procedures are also disclosed. Excerpt(s): This invention concerns novel methods and apparatus for medical applications, specifically wound closure applications. More particularly, the invention manipulates blood fluids, or its components, in new ways to close tissue or vascular wounds. Numerous medical applications exist where sealing of biological tissue is desired. U.S. Pat. No. 5,510,102 to Cochrum identifies many of these including trauma of liver, spleen, pancreas, lung, bone, etc., cardiovascular and vascular, such as microvascular anastomoses, vascular grafts, intraoperative bleeding, and aortic repair, for thoracic surgery such as lung biopsy, for transplant of heart, renal, pancreas, lung, bone or bone marrow, for neurosurgery such as nerve anastomoses, or CSF leak repair, for endoscopic surgery, such as hemostasis in hepatic trauma, or bile duct repair, for interventional radiology, such as hemostasis for percutaneous liver biopsy or vascular occlusion, for gastrointestinal surgery such as colonic anastomoses, for obstetrics and gynecology such as rectovaginal fistulas, for pediatric and fetal surgery, for plastic surgery and burn repairs such as grafting process of cultured epidermis, for dermatology such as hair transplants, for dental surgery, for ophthalmic cataract surgery, for urology, for correction of urinary fistulas and such others. With such broad application of the present invention possible, one use is selected for method and apparatus illustrative continuity purposes throughout this document. The selected application is sealing of a vascular wound resulting from percutaneous entry as is frequently done in the performance of angiography, angioplasty, and atherectomy procedures. Percutaneous vascular access is typically done in the context of performing some minimally invasive surgical procedure. Minimally invasive techniques are used to reduce trauma to the patient. Reduced trauma typically translates to improved patient comfort, less procedural complications, and lower costs. The vessel accessed is typically the femoral or radial artery. Access involves placement of an introducer's distal tip beneath the patient's skin and through the arterial wall. To the extent possible, percutaneous access preserves the integrity of tissue covering the artery. As a result, when the introducer is to be removed the arterial access site is not exposed and the arterial wound is preferably closed without cutting down through the overlaying tissue to expose the site.
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Device for and method of controlled enzymatic removal and retrieval of tissue Inventor(s): Freeman, Amihay; (Ben Shemen Youth Village, IL) Correspondence: G.E. Ehrlich (1995) LTD.; C/o Anthony Castorina; Suite 207; 2001 Jefferson Davis Highway; Arlington; VA; 22202; US Patent Application Number: 20030021775 Date filed: July 27, 2001 Abstract: Methods, devices and pharmaceutical compositions for the controlled, nonsurgical removal and retrieval of cells from a plurality of skin lesions and tissue surfaces are disclosed. A synergistic effect of proteolytic digestion of the intracellular matrix and "stripping" flow is achieved by treating a defined area with a controlled, continuous stream of proteolytic enzyme solution, causing gentle but effective tissue erosion. Isolated cells from the skin lesion and/or tissue surface may be collected from the protease solution stream for histological analysis and/or cell culture, affording a method of "enzymatic biopsy". The protease solution may be supplemented with anesthetics, coagulants, anticoagulants and antibiotics to decrease the discomfort, erythema, bleeding, risk of infection and scarring traditionally associated with surgical treatment of skin lesions. Furthermore, in the present invention delivery of precise levels of catalytic activity is ensured by controlled activation of stable, inactivated enzyme stock solutions and powders shortly prior to application. Excerpt(s): The present invention relates to a method, device and pharmaceutical composition for the controlled removal of cells from the surface of viable tissue by continuous local application of a solution containing a proteolytic enzyme and, more particularly, to a method, device and pharmaceutical composition for non-surgical, enzymatic treatment and biopsy of skin lesions. Tissues are composed of individual cells and cell groups, embedded in a proteinaceous extracellular matrix. Collagen fibers are the main component of this ubiquitous network, with other proteins such as fibronectin, laminin, elastin and tenascin, providing a mechanism for cell attachment. Cell surface attachment molecules, such as the CAM proteins, allow cells to adhere to the extracellular matrix and to neighboring cells. Thus, the histological integrity of tissues depends on the interaction of many protein and protein-derived molecules. Enzymes capable of digesting proteins, or proteases, are commonly employed to disrupt the extracellular matrix of tissues or tissue samples in order to separate cells for establishment of primary cell cultures (1). Proteases used in the isolation of cells for culturing are typically selective in their proteolytic activity or in the method of their application, achieving effective disruption of the matrix and adhesion proteins, yet causing minimal digestion of critical cell components. In the preparation of a primary culture, the tissue is mechanically cut into small (2-3 mm) pieces, these explants washed and gently agitated in an isotonic buffered solution containing a protease, such as trypsin or collagenase, for 30 minutes to several hours at room temperature. This procedure, resulting in suspended, isolated cells, is universal and has been employed for the preparation and propagation of primary cell cultures from a variety of tissues, including skin biopsies (2). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Glycosaminoglycans derived from K5 polysaccharide having high anticoagulant and antithrombotic activities and process for their preparation Inventor(s): Oreste, Pasqua; (Milano, IT), Zoppetti, Giorgio; (Milano, IT) Correspondence: Millen, White, Zelano & Branigan, P.C.; 2200 Clarendon BLVD.; Suite 1400; Arlington; VA; 22201; US Patent Application Number: 20020062019 Date filed: September 12, 2001 Abstract: Glycosaminoglycans derived from K5 polysaccharide having high anticoagulant and antithrombotic activity and useful for the control of coagulation and as antithrombotic agents are obtained starting from an optionally purified K5 polysaccharide by a process comprising the steps of N-deacetylation/N-sulfation, C5 epimerization, O-oversulfation, selective O-desulfation, 6-O-sulfation, N-sulfation, and optional depolymerization, in which said epimerization is performed with the use of the enzyme glucoronosyl C5 epimerase in solution or in immobilized form in the presence of divalent cations. New, particularly interesting antithrombin compounds are obtained by controlling the reaction time in the selective O-desulfation step and submitting the product obtained at the end of the final N-sulfation step to depolymerizazion. Excerpt(s): This application is a continuation-in-part of application Ser. No. 09/738,879 filed on Dec. 18, 2000. Glycosaminoglycans, such as heparin, heparan sulfate, dermatan sulfate, chondroitin sulfate and hyaluronic acid, are biopolymers industrially extracted from different animal organs. In particular heparin, principally obtained by extraction from intestinal pig mucosa or bovine lung, is a mixture of chains consisting of repeating disaccharide units formed by an uronic acid (L-iduronic acid or D-glucuronic acid) and by an amino sugar (glucosamine), joined by.alpha.-1.fwdarw.4 or.beta.-1.fwdarw.4 bonds. The uronic acid unit may be sulfated in position 2 and the glucosamine unit is Nacetylated or N-sulfated and 6-O sulfated. Moreover, glucosamine can contain a sulfate group in position 3 in an amount of about 0.5%. Heparin is a polydisperse copolymer with a molecular weight ranging from about 3,000 to about 30,000 D. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Heteroaryl aminoguanidines and alkoxyguanidines and their use as protease inhibitors Inventor(s): Lu, Tianbao; (Collegeville, PA), Markotan, Thomas P.; (Morgantown, PA), Siedem, Colleen; (Kennett Square, PA), Tomczuk, Bruce E.; (Collegeville, PA) Correspondence: Sterne, Kessler, Goldstein & Fox Pllc; 1100 New York Avenue, N.W., Suite 600; Washington; DC; 20005-3934; US Patent Application Number: 20020086872 Date filed: December 12, 2001 Abstract: Aminoguanidine and alkoxyguanidine compounds are described, including componds of the Formula VII: 1wherein X is O or NR.sup.9 and Het, R.sup.1, R.sup.7, R.sup.8, R.sup.12-R.sup.15 R.sup.a, R.sup.b, R.sup.c, Z, and n are set forth in the specification, as well as hydrates, solvates or pharmaceutically acceptable salts thereof, that inhibit proteolytic enzymes such as thrombin. Also described are methods for preparing such compounds. The compounds of the invention are potent inhibitors of proteases, especially trypsin-like serine proteases, such as chymotrypsin, trypsin,
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thrombin, plasmin and factor Xa. Certain of the compounds exhibit antithrombotic activity via direct, selective inhibition of thrombin. The invention includes a composition for inhibiting loss of blood platelets, inhibiting formation of blood platelet aggregates, inhibiting formation of fibrin, inhibiting thrombus formation, and inhibiting embolus formation in a mammal, comprising a compound of the invention in a pharmaceutically acceptable carrier. Other uses of compounds of the invention are as anticoagulants either embedded in or physically linked to materials used in the manufacture of devices used in blood collection, blood circulation, and blood storage, such as catheters, blood dialysis machines, blood collection syringes and tubes, blood lines and stents. Additionally, the compounds can be detectably labeled and employed for in vivo imaging of thrombi. Excerpt(s): This application claims benefit under 35 U.S.C.sctn. 119(e) of U.S. Provisional Application No. 60/079,107, filed Mar. 23, 1998, Appl. No. 60/067,324, filed Dec. 5, 1997, and Appl. No. 60/066,475, filed Nov. 26, 1997, the contents of all of which are fully incorporated by reference herein. The present invention relates to novel compounds that function as proteolytic enzyme inhibitors, and particularly to a new class of thrombin inhibitors. Proteases are enzymes that cleave proteins at single, specific peptide bonds. Proteases can be classified into four generic classes: serine, thiol or cysteinyl, acid or aspartyl, and metalloproteases (Cuypers et al., J. Biol. Chem. 257:7086 (1982)). Proteases are essential to a variety of biological activities, such as digestion, formation and dissolution of blood clots, reproduction and the immune reaction to foreign cells and organisms. Aberrant proteolysis is associated with a number of disease states in man and other mammals. The human neutrophil proteases, elastase and cathepsin G, have been implicated as contributing to disease states marked by tissue destruction. These disease states include emphysema, rheumatoid arthritis, corneal ulcers and glomerular nephritis. (Barret, in Enzyme Inhibitors as Drugs, Sandler, ed., University Park Press, Baltimore, (1980)). Additional proteases such as plasmin, C-1 esterase, C-3 convertase, urokinase, plasminogen activator, acrosin, and kallikreins play key roles in normal biological functions of mammals. In many instances, it is beneficial to disrupt the function of one or more proteolytic enzymes in the course of therapeutically treating a mammal. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Inhibition of tumor growth by a nematode anticoagulant protein Inventor(s): Green, Shawn J.; (Vienna, VA), Hembrough, Todd A.; (Damascus, MD) Correspondence: Kimberly J. Prior; Kilpatrick Stockton Llp; 2400 Monarch Tower; 3424 Peachtree Road, N.E.; Atlanta; GA; 30326; US Patent Application Number: 20020098176 Date filed: July 12, 2001 Abstract: The present invention relates to compositions and uses of nematode anticoagulant proteins (NAPs). More specifically, the invention relates to the use of rNAPc2 and rNAP5 for the inhibition of endothelial cell proliferation and the inhibition of angiogenesis. The invention also relates to methods for the treatment of angiogenesismediated diseases, such as cancer. Excerpt(s): This application claims priority to provisional application Serial No. 60/217,795 filed Jul. 12, 2000. The present invention relates to compositions and methods for the inhibition of cellular proliferation. More particularly, the present
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invention relates to the use of a nematode anticoagulant protein to inhibit angiogenesis. Cellular proliferation is a normal process in all living organisms and is one that involves numerous factors and signals that are delicately balanced to maintain regular cellular cycles. When normal cellular proliferation is disturbed or somehow disrupted, the results can be inconsequential or they can manifest an array of biological disorders such as cancer, abnormal development of embryo, improper formation of the corpus luteum, difficulty in wound healing as well as malfunctioning of inflammatory and immune responses. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Method and compositions for inhibiting thrombin-induced coagulation Inventor(s): Davis, Stacey; (College Station, TX), Hook, Magnus A.O.; (Houston, TX) Correspondence: Larson & Taylor, Plc; 1199 North Fairfax Street; Suite 900; Alexandria; VA; 22314; US Patent Application Number: 20030044418 Date filed: May 13, 2002 Abstract: A method of achieving safe and effective treatment or prevention of potentially harmful blood clots, or in inhibiting the coagulation of blood when so desired such as during a wide array of disease conditions including stroke, myocardial infarction, sickle-cell crisis and venous thrombosis, is provided by the administration of a fibrinogen-binding protein capable of binding at the N-terminal B.beta. chain of fibrinogen, such as SdrG or Fbe, or their respective binding regions such as the A domain. In addition, compositions comprising effective amounts of the fibrinogenbinding proteins are also provided. The present anti-coagulation compositions have been shown to inhibit thrombin-induced fibrin clot formation by interfering with the release of fibrinopeptide B and the resulting anti-coagulation effects can be achieved without potential for causing or exacerbating unwanted side effects such as thrombocytopenia associated with prior art anticoagulants such as heparin. Excerpt(s): This application claims the benefit of U.S. Provisional Patent Application No. 60/290,072, filed May 11, 2001. The present invention relates in general to SdrG, a fibrinogen-binding bacterial adhesin, and in particular to the use of SdrG or its binding region as an anti-coagulation agent by virtue of its ability to inhibit thrombin-induced fibrin clot formation by interfering with the release of fibrinopeptide B. In addition, the invention relates to methods and compositions utilizing SdrG or its binding region for treating or preventing thrombin-induced coagulation and conditions associated therewith. Coagulase-negative staphylococci (CNS) are important opportunistic pathogens that are particularly associated with foreign body infections in humans. Staphylococcus epidermidis is the most common pathogenic species of CNS and accounts for 74-92% of the infections caused by this group of staphylococci (1). The molecular pathogenesis of most infections is complex and involves multiple microbial factors and host components, but is generally initiated by the adherence of the microbe to host tissues. Bacterial adherence involves specific surface components called adhesins, and bacterial pathogens, such as staphylococci that live in the extracellular space of the host, target extracellular matrix (ECM) components, including fibrinogen (Fg) and fibronectin, for adherence and colonization. This process is mediated by a subfamily of adhesins that have been termed MSCRAMM.RTM.s (microbial surface components recognizing adhesive matrix molecules) (2). Staphylococcus aureus expresses multiple MSCRAMM.RTM.s of which several have been characterized in
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some detail (For a recent review see Ref. 3), and various MSCRAMM.RTM.s have been the subject of U.S. Patents, including fibronectin binding proteins such as disclosed in U.S. Pat. Nos. 5,175,096; 5,320,951; 5,416,021; 5,440,014; 5,571,514; 5,652,217; 5,707,702; 5,789,549; 5,840,846; 5,980,908; and 6,086,895; fibrinogen binding proteins such as disclosed in U.S. Pat. Nos. 6,008,341 and 6,177,084; and collagen binding proteins as disclosed in 5,851,794 and 6,288,214; all of these patents incorporated herein by reference. In addition, other information concerning SdrG and other MSCRAMM.RTM.s can be found in U.S. Ser. No. 09/810,428, filed Mar. 19, 2001, incorporated herein by reference; and U.S. Ser. No. 09/386,962, filed Aug. 31, 1999, incorporated herein by reference. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Nematode-extracted serine protease inhibitors and anticoagulant proteins Inventor(s): Bergum, Peter W.; (San Diego, CA), Gansemans, Yannick Georges Jozef; (Ichtegem, BE), Jespers, Laurent Stephane; (Tervuren, BE), LaRoche, Yves Rene; (Bruxelles, BE), Lauwereys, Marc Josef; (Haaltert, BE), Messens, Joris Hilda Lieven; (Dilbeek, BE), Moyle, Matthew; (Thousand Oaks, CA), Stanssens, Patrick Eric Hugo; (StMartens-Latem, BE), Vlasuk, George Phillip; (Carlsbad, CA) Correspondence: Suzanne L Biggs; Lyon & Lyon Llp; 633 West Fifth Street 47th Floor; Los Angeles; CA; 90071; US Patent Application Number: 20030113890 Date filed: February 4, 2000 Abstract: Proteins which have activity as anticoagulants and/or serine protease inhibitors and have at least one NAP domain and are described. Certain of these proteins have factor Xa inhibitory activity and others have activity as inhibitors of factor VIIa/TF. These proteins can be isolated from natural sources as nematodes, chemically synthesized or made by recombinant methods using various DNA expression systems. Excerpt(s): This application is a Continuation-in-Part of U.S. Ser. Nos. 08/461,965, 08/465,380, 08/486,397 and 08/486,399, all filed on Jun. 5, 1995, each of which is a continuation-in-part of U.S. Ser. No. 08/326,110, filed Oct. 18, 1995; the disclosures of all these applications are incorporated herein by reference. The present invention relates to specific proteins as well as recombinant versions of these proteins; which are serine protease inhibitors, including potent anticoagulants in human plasma. These proteins include certain proteins extracted from nematodes. In another aspect, the present invention relates to compositions comprising these proteins, which are useful as potent and specific inhibitors of blood coagulation enzymes in vitro and in vivo, and methods for their use as in vitro diagnostic agents, or as in vivo therapeutic agents, to prevent the clotting of blood. In a further aspect, the invention relates to nucleic acid sequences, including mRNA and DNA, encoding the proteins and their use in vectors to transfect or transform host cells and as probes to isolate certain related genes in other species and organisms. Normal hemostasis is the result of a delicate balance between the processes of clot formation (blood coagulation) and clot dissolution (fibrinolysis). The complex interactions between blood cells, specific plasma proteins and the vascular surface, maintain the fluidity of blood unless injury occurs. Damage to the endothelial barrier lining the vascular wall exposes underlying tissue to these blood components. This in turn triggers a series of biochemical reactions altering the hemostatic balance in favor of blood coagulation which can either result in the desired formation of a hemostatic plug
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stemming the loss of blood or the undesirable formation of an occlusive intravascular thrombus resulting in reduced or (complete lack of blood flow to the affected organ. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Novel tissue factor targeted thrombomodulin fusion proteins as anticoagulants Inventor(s): Light, David; (San Mateo, CA), McLean, Kirk; (Oakland, CA) Correspondence: Berlex Biosciences; Patent Department; 2600 Hilltop Drive; P.O. Box 4099; Richmond; CA; 94804-0099; US Patent Application Number: 20040063632 Date filed: April 30, 2003 Abstract: This invention relates to novel fusion proteins which are comprised of a targeting protein that binds tissue factor (TF), which is operably linked to the thrombomodulin (TM) EGF456 domain alone or in combination with at least one other TM domain selected from the group consisting of the N-terminal hydrophobic region domain, the EGF123 domain, the interdomain loop between EGF3 and EGF4, and the Oglycosylated Ser/Thr-rich domain, or analogs, fragments, derivatives or variants thereof. The fusion protein binds at the site of injury and prevents the initiation of thrombosis. The fusion protein can be used to treat a variety of thrombotic conditions including but not limited to deep vein thrombosis, disseminated intravascular coagulation, and acute coronary syndrome. Excerpt(s): This application claims the benefit of U.S. Provisional Application Serial No. 60/376,566, filed May 1, 2002, which is incorporated herein in full by reference. Maintaining the proper balance between procoagulant and anticoagulant activity within blood vessels is essential for normal hemostasis (Davie, E. W. et al. (1991) Biochemistry, 30(43):10363-10370). Perturbing the balance toward coagulation leads to thrombosis, which can cause heart attack, stroke, pulmonary embolism, and venous thrombosis. There is a need for more effective and safer anticoagulants for the treatment of specific thrombotic disorders. Tissue factor ("TF") is a transmembrane glycoprotein that is the major initiator of the coagulation cascade (Nemerson, Y. (1995) Thromb. Haemost. 74(1):180-184). Under normal physiological conditions active TF is not in contact with blood. During vascular injury, exposure to blood of subendothelial TF and collagen leads to activation of coagulation factors and platelets and subsequently to hemostatic plug formation. The inappropriate induction of TF expression in a variety of clinical settings can lead to life threatening thrombosis and/or contribute to pathological complications. TF exposure following plaque rupture is believed to be responsible for thrombotic occlusion leading to acute myocardial infarction and stroke. In these settings, proinflammatory signaling pathways activated by coagulation factors also contribute to edema formation and increased infarct size. Vascular injury associated with angioplasty leads to upregulation of TF on SMC's which is believed to induce cell signaling pathways associated with restenosis. TF overexpression in cancer and gram-negative sepsis leads to life threatening thrombosis and activation of inflammatory pathways. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Onset of force development as a marker of thrombin generation Inventor(s): Carr, Marcus JR.; (Midlothian, VA) Correspondence: Whitham, Curtis & Christofferson, P.C.; 11491 Sunset Hills Road; Suite 340; Reston; VA; 20190; US Patent Application Number: 20030199428 Date filed: April 3, 2003 Abstract: Platelet contractile force (PCF) is used as a surrogate marker of thrombin generation. PCF generation occurs concomitant with the burst of prothrombin fragment F 1+2 release. The time between assay start and PCF onset is identified as the thrombin generation time (TGT), and is used in assessing risk of bleeding, in diagnosing various disorders, and in monitoring the effects of pharmaceutical and other treatments. TGT is prolonged in clotting factor deficiencies and in the presence of direct and indirect thrombin inhibitors. TGT shortens to normal with clotting factor replacement and shortens with administration of rVIIa. TGT is short in thrombophilic states such as coronary artery disease, diabetes and thromboangiitis obliterans and prolongs toward normal with oral and intravenous anticoagulants. Excerpt(s): The invention is related to a method, instrumentation, and treatments which use the onset of platelet contractile force (PCF) as a surrogate marker thrombin generation. Thrombin generation is increasingly recognized as the critical component of normal hemostatic function. If thrombin formation is delayed as in various clotting factor deficiencies the individual is at risk for excessive bleeding. If thrombin generation is too rapid or incompletely controlled, as in thrombophilic states, the patient is at risk for recurrent thrombosis. Therapeutic interventions in both cases are geared at reversing abnormal thrombin generation either by speeding it up with hemostatic agents or slowing it down with anticoagulants. Routine coagulation screens such as the prothrombin and partial thromboplastin time use fibrin formation as a surrogate marker of thrombin generation. Unfortunately, these studies are routinely performed in platelet poor plasma and thereby miss the potential effects of cellular elements on the rate of thrombin formation. The critical role played by tissue bearing cells and activated platelets is increasingly recognized (1,2). The continuing development of potent antiplatelet and anticoagulant agents and their combined application in settings such as acute coronary syndromes and cerebrovascular attacks have emphasized the need for a global measure of thrombin generation which could reflect the combined effects of these agents. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Plasma glucosylceramide deficiency as risk factor for thrombosis and modulator of anticoagulant protein C Inventor(s): Deguchi, Hiroshi; (Del Mar, CA), Fernandez, Jose; (La Jolla, CA), Griffin, John H.; (Del Mar, CA) Correspondence: Morgan & Finnegan, L.L.P.; 345 Park Avenue; New York; NY; 101540053; US Patent Application Number: 20020177563 Date filed: February 28, 2002
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Abstract: The present invention has determined that exogenously added glycosylceramide (GlcCer) and other neutral glycolipids such as the homologous Glccontaining globotriaosylceramide (Gb3Cer), dose-dependently prolonged clotting times of normal plasma in the presence but not absence of APC:protein S, indicating GlcCer or Gb3Cer can enhance protein C pathway anticoagulant activity. In studies using purified proteins, inactivation of factor Va by APC:protein S was enhanced by GlcCer alone and by GlcCer, globotriaosylceramide, lactosylceramide, and galactosylceramide in multicomponent vesicles containing phosphatidylserine and phosphatidylcholine. Thus, the present invention provides neutral glycolipids such as GlcCer and Gb3Cer, as anticoagulant cofactors that contribute to the antithrombotic activity of the protein C pathway. The present invention has also determined that a deficiency of plasma GlcCer is a risk factor for thrombosis. Methods are provided to determine individuals at risk for thrombosis, methods of treatment as well as methods of screening for antithrombotic factors from neutral glycolipids. Excerpt(s): This application claims benefit to Provisional Application No. 60/272,103, filed Feb. 28, 2001, and Provisional Application No. 60/278,045, filed Mar. 22, 2001. The present invention relates to neutral glycolipids as antithrombotic factors for prevention or inhibition of thrombosis and as anti-inflammatory agents. More specifically the invention relates to neutral glycolipids such as glucosylceramide, globotriaosylceramide, galactosylceramide, lactosylceramide and the like as antithrombotic factors and the use of the neutral glycolipids for prevention or inhibition of thrombosis and as anti-inflammatory agents. The present invention also relates to methods for screening for individuals at risk of thrombosis and relates to methods of screening for antithrombolytic agents from candidate neutral glycolipids. Blood coagulation reactions are stimulated by phospholipid membrane surfaces as is the anticoagulant protein C pathway. (17) However, procoagulant and anticoagulant complexes may be differentially affected by different membrane phospholipid components. (18-20) Because we found that high density lipoprotein (HDL) exhibits anticoagulant cofactor activity for APC:protein S (21) we decided to evaluate further the influence of plasma lipids and lipoproteins on the protein C pathway. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Prosthetic heart valve Inventor(s): Cartledge, Richard G.; (Boca Raton, FL), Lee, Leonard; (New York, NY) Correspondence: Smith, Gambrell & Russell, Llp; Suite 3100, Promenade II; 1230 Peachtree Street, N.E.; Atlanta; GA; 30309-3592; US Patent Application Number: 20030069635 Date filed: May 28, 2002 Abstract: A novel durable prosthetic heart valve compatible with implantation in a human natural heart valve annulus. The prosthetic heart valve comprises a tubular heart valve which in function resembles a human heart valve, but which is formed of either synthetic or biologic material. The present valve is capable of structurally complying with annular deformation during each heartbeat. Valve embodiments comprise aortic, mitral, tricuspid, and pulmonic implantable valves. Valves can be selectively impregnated with a group of biologically active substances consisting of antibiotics, bactericidal agents, anticoagulant medications, endothelial cells, genetic material, growth factors or other hormonal or biologically active substances. Use of nonthrombogenic biocompatible materials in the valve which mimics operation of a natural
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heart valve essentially eliminates the need for long term administration of anticoagulants. The current configuration of the valve allows for either percutaneous placement or placement through open techniques. Excerpt(s): This application is related to provisional patent application No. 60/294,042 filed May 29, 2001. This invention relates to implantable heart valves and in particular to long-lasting implantable prosthetic heart valves comprising valve leaflets made from synthetic or biologic materials. The present invention also relates to flexible leaflet heart valves that are used to replace the natural aortic, mitral, tricuspid, or pulmonary valves of the heart. These valves are designed to be placed either percutaneously or by traditional approaches. A multiplicity of replacement heart valve prostheses are generally known in the art. A first replacement type comprises totally mechanical heart valves which effect unidirectional blood flow through the use of a device using a mechanical closure. Earlier mechanical heart valves comprise pressure responsive, pressure directed movement of a ball in a cage or tilting or caged discs. Other valves known as "tissue valves" utilize either processed cadaveric valves known in the art as homografts, processed and mounted animal valves, or specially prepared and mounted biologic tissues that function as a valve such as bovine pericardial valves. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Reagent kit for detecting lupus anticoagulant Inventor(s): Okuda, Masahiro; (Kobe-shi, JP) Correspondence: Sughrue Mion, Pllc; 2100 Pennsylvania Avenue, N.W.; Suite 800; Washington; DC; 20037; US Patent Application Number: 20040091952 Date filed: July 21, 2003 Abstract: A reagent kit capable of distinguishing between a blood sample containing lupus anticoagulant and blood samples from individuals having other anticoagulant diseases is disclosed. The reagent kit comprises two coagulation time reagents containing phosphatidylserine in a different phosphatidylserine content ratio to the total content of phospholipids from each other, threreby giving different coagulation times with use of corresponding coagulation time reagent. Excerpt(s): This invention relates to a blood coagulation reagent kit used in diagnosis of anti-phospholipid (aPL) antibody syndrome in the fields such as a clinical chemistry and a medical study, and more particularly pertains to a reagent kit capable of specifically detecting lupus-anticoagulant-positive diseases based on a blood test in vitro. Lupus anticoagulant (hereinafter, called as "LA") is an immunoglobulin which has been found firstly in patients suffering from systemic lupus erythematosus (hereinafter, called as "SLE patients"). While LA is detected in SLE patients with a frequency ranging from 5 to 10%, it is also detected in patients suffering from other autoimmune diseases and tumorous diseases. LA is most frequently detected in patients with anti-phospholipid syndrome (APS) such as patients with thrombosis, women who have undergone miscarriage or premature labor, and patients with thrombocytopenia. Since a time required in blood coagulation with respect to patients with APS is prolonged owing to phospholipid-dependent coagulation reaction, it is conceived that LA is an autoantibody against phospholipid. According to a recent study, it has been elucidated that LA is a heterogeneous immunoglobulin which shows antibody reaction against a complex of negatively-charged phospholipid and.beta.2-glycoprotein I (.beta.2-GPI) or a
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complex of negatively-charged phospholipid and prothrombin. It is conceived that LA causes anti-coagulating action because bonding of LA to the complex hinders conversion of prothrombin to thrombin. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Salicylamides as serine protease and factor xa inhibitors Inventor(s): Allen, Darin Arthur; (Daly City, CA), McGee, Danny Peter Claude; (Vista, CA), Spencer, Jeffrey R; (South San Francisco, CA) Correspondence: Townsend And Townsend And Crew, Llp; Two Embarcadero Center; Eighth Floor; San Francisco; CA; 94111-3834; US Patent Application Number: 20030232789 Date filed: October 24, 2002 Abstract: The present invention provides novel compounds of Formula (I), its prodrug forms, or pharmaceutically acceptable salts thereof. The compounds of this invention are inhibitors of serine proteases, Urokinase (uPA), Factor Xa (FXa), and/or Factor VIIa (FVIIa), and have utility as anti cancer agents and/or as anticoagulants for the treatment or prevention of thromboembolic disorders in mammals. The present invention also provides a process for the selective acylation of an amino group. 1 Excerpt(s): The present invention relates to novel serine protease inhibitors. One of the most active areas in cancer research is in the field of proteolytic enzymes and their role in the spread of cancer. One class of proteases that plays a significant role in the progression of cancer are the serine proteases, in particular Urokinase-type plasminogen activator (uPA). Inhibitors of uPA have been postulated to be of therapeutic value in treating cancer. Inhibitors of these serine proteases also tend to be inhibitors of the closely related blood-clotting enzymes. One such blood-clotting enzyme is Factor Xa. Factor Xa (herein after "FXa"), the converting enzyme of pro-thrombin to thrombin, has emerged as an alternative target (to thrombin) for drug discovery for thromboembolic disorders. A variety of compounds have been developed as potential FXa inhibitors. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Spray dry process for applying anticoagulant on a syringe barrel Inventor(s): Barkell, Paul; (Plymouth, GB), Church, Stephen; (Plymouth, GB) Correspondence: Kirk M. Miles; Webb Ziesenheim Logsdon Orkin & Hanson, P.C.; 700 Kopper Building; 436 Seventh Avenue; Pittsburgh; PA; 15219-1818; US Patent Application Number: 20030120198 Date filed: November 13, 2002 Abstract: A method for coating a substrate surface, such as an interior portion of a syringe is provided. An aqueous anticoagulant solution is atomized onto the substrate surface and dried by the forced flow of warm air. Water is removed during the drying leaving a coating of anticoagulant. A concentrated aqueous anticoagulant solution is used to reduce the time required for drying. A syringe having an interior portion coated with anticoagulant is also provided.
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Excerpt(s): This application claims the benefit of U.S. Provisional Application Ser. No. 60/350,613 filed Nov. 13, 2001 which is incorporated by reference in its entirety. The present invention is directed to a method for applying anticoagulants to a substrate. More particularly, the present invention is directed to a spray dry process for applying anticoagulants onto a syringe barrel. Syringes are often used to take blood samples from patients. In some cases it is desirable for the blood sample not to clot. In such cases an anticoagulant is typically added to the syringe to prevent the clotting of the blood sample. The addition of an anticoagulant is often performed at the manufacturing step as compared to a medical technician adding a quantity of anticoagulant prior to the taking of a blood sample. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Substituted benzene derivatives or salts thereof Inventor(s): Hirayama, Fukushi; (Ibaraki, JP), Ishihara, Tsukasa; (Ibaraki, JP), Kadokura, Takeshi; (Ibaraki, JP), Koga, Yuji; (Ibaraki, JP), Shigenaga, Takeshi; (Ibaraki, JP), Sugasawa, Keizo; (Ibaraki, JP) Correspondence: Fitzpatrick Cella Harper & Scinto; 30 Rockefeller Plaza; New York; NY; 10112; US Patent Application Number: 20040077555 Date filed: September 10, 2003 Abstract: There are provided compounds having an anticoagulant action on the basis of inhibition of activated blood coagulation factor X and being useful as anticoagulants or preventive/therapeutic agents for diseases induced by thrombosis or embolism. Effective ingredients are the compounds such as 4'-bromo-2'-[(5-chloro-2pyridyl)carbamoyl]-6'-.beta.-D-galactopyranosyloxy-1-isopropylpiperidine-4carboxanilide, 2'-(2-acetamido-2-deoxy-.beta.-D- -glucopyranosyloxy)-4'-bromo-6'-[(5chloro-2-pyridyl)carbamoyl]-1-isopropy- lpiperidine-4-carboxanilide, etc. or salts thereof. Excerpt(s): The present invention relates to a novel substituted benzene derivative or a salt thereof which is useful as a pharmaceutical agent particularly as an activated blood coagulation factor X inhibitor and also to such a pharmaceutical agent. With the changes into European and American life styles and the increase in aged population in recent years, the number of patients with thromboembolic diseases including myocardial infarction, cerebral thrombosis and peripheral arterial thrombosis have been increasing year by year and social importance of their treatment has been increasing more and more. As well as the fibrinolysis therapy and antiplatelet therapy, the anticoagulation therapy takes a part of the medical therapy in treating and preventing thrombosis (Sogo Rinsho, 41: 2141-2145, 1989). In particular, the safety which withstands long-term administration and accurate and proper expression of the anticoagulation activity are essential in the prevention of thrombosis. Warfarin potassium is frequently used in the world as the sole oral anticoagulant but this drug is extremely difficult to use clinically because it is difficult to control the anticoagulation capacity due to the characteristics based on its action mechanism (J. Clinical Pharmacology, 32, 196-209, 1992 and N. Eng. J. Med., 324(26), 1865-1875, 1991) whereby a great concern has been directed toward the development of more useful and easily usable anticoagulants. Thrombin controls conversion of fibrinogen into fibrin which is the final step of coagulation and is also concerned deeply in the activation and aggregation of platelets ("T-PA and Pro-UK" edited by S. Matsuo, published by Gakusai Kikaku, pp. 5-40 "Blood Coagulation", 1986)
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and its inhibitor has been the center of anticoagulant studies as a target of development of pharmaceuticals. However, thrombin inhibitors which can be administered orally have not been put into the market until now because of their low bioavailability by oral administration and problems from the viewpoint of safety (Biomed. Biochim. Acta, 44, 1201-1210, 1985). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Wearable ultrafiltration device Inventor(s): Gura, Victor; (Beverly Hills, CA) Correspondence: Mitchell P. Brook, ESQ.; Luce Forward Hamilton & Scripps Llp; Suite 200; 11988 EL Camino Real; San Diego; CA; 92130; US Patent Application Number: 20030097087 Date filed: September 19, 2002 Abstract: An ultrafiltration device adapted to be worn on a portion of the body of a patient includes a blood inlet tube leading from a first blood vessel, a blood pump, an anticoagulant reservoir for infusing anticoagulants into the blood, a blood filter including a substrate through which the blood is circulated and filtered, a fluid bag for storing the excess fluid and a blood outlet tube leading to a second blood vessel. Excerpt(s): This application is a continuation-in-part of U.S. patent application Ser. No. 10/085,349, filed Nov. 16, 2001, which is hereby incorporated by reference. The present invention is directed to ultrafiltration devices, and more particularly to a portable ultrafiltration device that may be continuously worn by a patient. Fluid overload can be caused by many things including metabolic disease, renal failure and, especially, congestive heart failure (CHF), which has become a disease of epidemic proportions all over the globe. CHF is a progressive deterioration of the heart muscle that leads to an inability to pump enough blood to support the vital organs. Deterioration of the heart muscle leads to decreased pumping capacity and increased fluid retention caused by the lack of perfusion pressure of the kidneys due to the failure of the heart to pump enough blood at the proper pressure. Fluid overload can cause leg swelling, shortness of breath and water accumulation in the lungs, impairing the ability to properly breathe. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Wound closure system and methods Inventor(s): Luthra, Ajay K.; (Ruislip, GB), Onis, Simon Jon; (Brentwood, GB), Sandhu, Shivpal S.; (Slough, GB) Correspondence: Patterson, Thuente, Skaar & Christensen, P.A.; 4800 Ids Center; 80 South 8th Street; Minneapolis; MN; 55402-2100; US Patent Application Number: 20030018357 Date filed: May 9, 2002 Abstract: A wound closure system and methods utilizes a patient's own blood. The system preferably includes a chamber with a needle and a plunger for transferring and storing blood prior to surgery and the use of reversible anticoagulants. The chamber is pre-loaded with a reversible anticoagulant to prevent the blood from clotting during storage. When the surgery is complete, a counteracting agent is mixed with the
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withdrawn blood to counteract the reversible anticoagulant and allow the blood to clot. The clottable blood is then reintroduced into the patient to close a wound. Excerpt(s): This application claims priority to U.S. provisional patent application serial number 60/289,754, filed May 9, 2001, entitled "Wound Closure System and Methods", which is hereby incorporated herein by reference. The invention relates to wound closure systems that use a patient's own blood. More specifically, the invention relates to withdrawing blood from a patient and readministering the blood as a wound closure system. Patients are often treated systemically with anticoagulants that prevent their blood from clotting. Anticoagulants are typically used during medical procedures that require introducing a medical instrument into a patient's body through an artery. An example of such a procedure is a percutaneous transluminal coronary angioplasty (PTCA), which involves introducing a stent through the arteries. Such procedures leave a puncture wound in the artery where the medical instruments, such as a PTCA catheter, are introduced. The puncture extends through the skin, through the tissue under the skin, and into the artery. 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 anticoagulants, 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 “anticoagulants” (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 anticoagulants. You can also use this procedure to view pending patent applications concerning anticoagulants. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.
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CHAPTER 6. BOOKS ON ANTICOAGULANTS Overview This chapter provides bibliographic book references relating to anticoagulants. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on anticoagulants 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 “anticoagulants” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “anticoagulants” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “anticoagulants” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •
A Guide to Oral Anticoagulant Therapy by S. Coccheri; ISBN: 3805567774; http://www.amazon.com/exec/obidos/ASIN/3805567774/icongroupinterna
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Australian National Meeting on Lupus Anticoagulant (Hematology Reviews and Communications Series) by S. Roath, M. Corn; ISBN: 3718649357; http://www.amazon.com/exec/obidos/ASIN/3718649357/icongroupinterna
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Blood, Coagulants and Anticoagulants to Cardiovascular Agents, Volume 4, Encyclopedia of Chemical Technology, 3rd Edition by Kirk Othmer; ISBN: 0471020400; http://www.amazon.com/exec/obidos/ASIN/0471020400/icongroupinterna
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Drugs of Tomorrow 2001: Anticoagulants - A pipeline flowing with future blockbusters [DOWNLOAD: PDF] by Datamonitor; ISBN: B00008R3NO; http://www.amazon.com/exec/obidos/ASIN/B00008R3NO/icongroupinterna
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New Anticoagulants for the Cardiovascular Patient by Roque Pifarre; ISBN: 1560532203; http://www.amazon.com/exec/obidos/ASIN/1560532203/icongroupinterna
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Thromboplastin Calibration and Oral Anticoagulant Control by A. M. H. P. Van Den Besselaar; ISBN: 0898386373; http://www.amazon.com/exec/obidos/ASIN/0898386373/icongroupinterna
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Thrombosis in Cancer - Expanding Focus for Anticoagulants [DOWNLOAD: PDF] by Datamonitor; ISBN: B0000X8URM; http://www.amazon.com/exec/obidos/ASIN/B0000X8URM/icongroupinterna
Chapters on Anticoagulants In order to find chapters that specifically relate to anticoagulants, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and anticoagulants 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 “anticoagulants” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on anticoagulants: •
Treatment of Acute Rejection Source: in Tejani, A.H. and Fine, R.N., eds. Pediatric Renal Transplantation. New York, NY: Wiley-Liss. 1994. p. 279-290. Contact: Available from John Wiley and Sons, Inc. 1 Wiley Drive, Somerset, NJ 088751272. (800) 225-5945. PRICE: $99.95 (as of 1995). ISBN: 0471591203. Summary: In this chapter, from a medical text about pediatric renal transplantation, the author outlines the standard procedures of antirejection treatments, with a special emphasis on those at the Children's Hospital and Medical School, Hannover, Germany. Topics covered include the use of glucocorticosteroids; polyclonal immunoglobulins (ALG, ATG); monoclonal antibodies (OKT3); FK506; plasmapheresis; and irradiation. For each treatment, the author provides information on the recommended dosage and administration, the side effects to watch for, and the results to be anticipated. Additional sections cover CMV prophylaxis during antirejection therapy and anticoagulants in antirejection treatment. 2 figures. 5 tables. 59 references.
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Radical Retropubic Prostatectomy Source: in Graham, S.D., Jr., et al., eds. Glenn's Urologic Surgery. 5th ed. Philadelphia, PA: Lippincott Williams and Wilkins. 1998. p. 275-284. Contact: Available from Lippincott Williams and Wilkins. P.O. Box 1600, Hagerstown, MD 21741. (800) 638-3030 or (301) 714-2300. Fax (301) 824-7390. Website: lww.com. PRICE: $199.00 plus shipping and handling. ISBN: 0397587376. Summary: The unprecedented increase in the incidence of carcinoma of the prostate that has occurred over the last decade has resulted in a corresponding increase in the rate with which radical prostatectomy is performed. Refinements in patient selection and surgical technique have diminished the morbidity of surgery. This chapter on radical
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retropubic prostatectomy is from an exhaustive textbook on urologic surgery. Radical prostatectomy is indicated in patients with carcinoma of the prostate seemingly confined within the surgical capsule of the gland, who would be expected to have a life expectancy of at least 10 years. Thus, appropriate patient selection requires accurate tumor staging as well as an assessment of patient comorbidity. The author details the surgical technique used and reviews the complications and results that can be anticipated. Thromboembolic problems remain the most frequent cause of serious morbidity and occasional mortality after radical retropubic prostatectomy. Clinically recognized deep venous thrombosis occurs in 3 to 5 percent, and pulmonary embolus in 1 to 3 percent of patients. Routine use of anticoagulants in the perioperative period diminishes the rate of thromboembolic complications but does introduce a risk of wound or operative site bleeding or hematoma. The most troubling long term complications of radical prostatectomy are the possibilities of impotence or incontinence. The risk of impotence is directly related to patient age, potency status before surgery, and the choice of a unilateral or bilateral nerve sparing approach. Incontinence requiring further treatment occurs in around 2 percent of patients, but up to 15 to 20 percent of patients have at least occasional episodes of stress incontinence. 17 figures. 11 references. •
Hemodialysis and Hemofiltration Source: in Greenberg, A., et al., eds. Primer on Kidney Diseases. New York, NY: National Kidney Foundation. 1994. p. 258-265. Contact: Available from Academic Press. Order Fulfillment, 6277 Sea Harbor Drive, Orlando, FL 32887. (800) 321-5068. PRICE: Paperback $49.95 (paper). ISBN: 0122992318. OR $99 (hardback). ISBN: 012299230X. Summary: This chapter, from a comprehensive textbook of clinical nephrology, focuses on hemodialysis and hemofiltration. Topics covered include the structure of hemodialyzers and hemofilters; the types of extracorporeal therapy for renal failure; hemodialysis and hemofiltration membranes and machines; water transport and solute clearance profiles; dialysate; vascular access; anticoagulants; indications for hemodialysis and hemofiltration; quantitation of hemodialysis; complications of hemodialysis; dialyzer reuse; and drug usage in hemodialysis. 2 figures. 2 tables. 11 references.
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Cerebrovascular Disease Source: in Clinician's Guide to Treatment of Medically Compromised Patients. Baltimore, MD: American Academy of Oral Medicine (AAOM). 1995. p. 17-19. Contact: Available from American Academy of Oral Medicine (AAOM). 2910 Lightfoot Drive, Baltimore, MD 21209-1452. (410) 602-8585. Website: www.aaom.com. PRICE: $21.00 plus shipping and handling. Summary: This chapter, from a guide for dentists on managing problems of medically compromised dental patients, discusses cerebrovascular disease. The authors provide a definition of cerebrovascular accident (CVA)/stroke syndrome; describe its etiology and clinical presentation; and outline emergency treatment. One chart outlines the different types of strokes and their presentation; another chart outlines drug therapy, primarily anticoagulants, related to prevention.
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CHAPTER 7. PERIODICALS ANTICOAGULANTS
AND
NEWS
ON
Overview In this chapter, we suggest a number of news sources and present various periodicals that cover anticoagulants.
News Services and Press Releases One of the simplest ways of tracking press releases on anticoagulants 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 “anticoagulants” (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 anticoagulants. 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 “anticoagulants” (or synonyms). The following was recently listed in this archive for anticoagulants: •
Survival after Ebola exposure prolonged in primates given anticoagulant protein Source: Reuters Industry Breifing Date: December 11, 2003
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•
New anticoagulant effective as warfarin, does not require regular blood monitoring Source: Reuters Medical News Date: April 04, 2003
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Despite bleeding risk, anticoagulants may benefit dialysis patients with AF Source: Reuters Industry Breifing Date: March 10, 2003
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AstraZeneca upbeat on anticoagulant results Source: Reuters Industry Breifing Date: February 17, 2003
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AstraZeneca's Exanta "inferior" to Sanofi anticoagulant rival Source: Reuters Industry Breifing Date: January 24, 2003
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Oral anticoagulants more effective than aspirin at reducing atrial fibrillation-related stroke risk Source: Reuters Industry Breifing Date: November 20, 2002
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AstraZeneca upbeat on anticoagulant Exanta Source: Reuters Industry Breifing Date: November 07, 2002
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HemoSense earns FDA okay for at-home anticoagulant test Source: Reuters Industry Breifing Date: November 05, 2002
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FDA approves at-home anticoagulant test Source: Reuters Medical News Date: November 05, 2002
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Novel anticoagulant created from aptamer-antidote pairs Source: Reuters Industry Breifing Date: September 04, 2002
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St. Jude to sell LifeScan's anticoagulant monitor to cardiac market Source: Reuters Industry Breifing Date: September 05, 2001 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.
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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 “anticoagulants” (or synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests. Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “anticoagulants” (or synonyms). If you know the name of a company that is relevant to anticoagulants, 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 “anticoagulants” (or synonyms).
Academic Periodicals covering Anticoagulants Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to anticoagulants. In addition to these sources, you can search for articles covering anticoagulants 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 8. 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 anticoagulants. 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 anticoagulants. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.). The
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following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to anticoagulants: 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
Dipyridamole Therapeutic •
Systemic - U.S. Brands: Persantine http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202624.html
Heparin •
Systemic - U.S. Brands: Calciparine; Liquaemin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202280.html
Tinzaparin •
Systemic - U.S. Brands: Innohep http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500175.html
Vitamin K •
Systemic - U.S. Brands: AquaMEPHYTON; Mephyton http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202599.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/.
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PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee. If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.
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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.
NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute10: •
Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm
•
National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/
•
National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html
•
National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25
•
National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm
•
National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm
•
National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375
•
National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/
10
These publications are typically written by one or more of the various NIH Institutes.
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•
National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm
•
National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/
•
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm
•
National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm
•
National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/
•
National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/
•
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm
•
National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html
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National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm
•
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
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National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm
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Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp
•
National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/
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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
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Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm
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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.11 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:12 •
Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html
•
HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html
•
NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html
•
Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/
•
Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html
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Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html
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Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/
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Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html
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Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html
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Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html
•
MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html
11 Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 12 See http://www.nlm.nih.gov/databases/databases.html.
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Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html
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Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html
The NLM Gateway13 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.14 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “anticoagulants” (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 128640 306 1014 106 158 130224
HSTAT15 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.16 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.17 Simply search by “anticoagulants” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
13
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
14
The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 15 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 16 17
The HSTAT URL is http://hstat.nlm.nih.gov/.
Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.
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Coffee Break: Tutorials for Biologists18 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.19 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.20 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.
Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •
CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.
•
Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.
18 Adapted 19
from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.
The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 20 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.
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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on anticoagulants 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 anticoagulants. 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 anticoagulants. 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 “anticoagulants”:
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Bleeding Disorders http://www.nlm.nih.gov/medlineplus/bleedingdisorders.html Heart Attack http://www.nlm.nih.gov/medlineplus/heartattack.html Heart Diseases http://www.nlm.nih.gov/medlineplus/heartdiseases.html Pulmonary Embolism http://www.nlm.nih.gov/medlineplus/pulmonaryembolism.html Stroke http://www.nlm.nih.gov/medlineplus/stroke.html Thrombophlebitis http://www.nlm.nih.gov/medlineplus/thrombophlebitis.html Transient Ischemic Attack http://www.nlm.nih.gov/medlineplus/transientischemicattack.html You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on anticoagulants. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: •
What is Lupus? Source: Washington, DC: Lupus Foundation of America. 2002. 6 p. Contact: Available from Lupus Foundation of America. 2000 L. St., Suite 710, Washington, DC 20036-4916. (202) 349-1155 or (800) 558-0121. (800) 558-0231 (information in Spanish). Fax: (202) 349-1156. Website: www.lupus.org. Summary: This brochure discusses lupus, a chronic autoimmune condition that affects various parts of the body including the skin, joints, blood, and kidneys. Scientists believe that both environment and genetics play a role in triggering lupus. Lupus is more common in women. There are three types of lupus: discoid or cutaneous (DL), systemic (SL), and drug-induced. DL is limited to the skin and characterized by a rash that appears on the scalp, neck, or face but does not involve the body's internal organs. SL is generally more severe than DL and affects organs and systems in the body. Druginduced lupus can occur after using certain prescription drugs and is found primarily in
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men. The symptoms of drug-induced lupus are similar to those of SL. The most common symptoms of lupus and criteria used to diagnosis lupus are listed. Tests used to diagnose lupus include the lupus erythematosus test and the immunofluorescent antinuclear antibody test. Treatment for lupus focuses on reducing symptoms and inflammation and maintaining normal body functions. Medications are prescribed based on the organs involved and the severity of this involvement. Commonly prescribed medications include NSAIDs, acetaminophen, corticosteroids, antimalarials, immunomodulating drugs, and anticoagulants. The brochure also discusses pregnancy and lupus as well as the prognosis for patients with lupus. 2 tables. •
Ginkgo Biloba Source: Silver Spring, MD: ADEAR Center. 1998. One page, eight panels. Contact: ADEAR Center. PO Box 8250, Silver Spring, MD 20907-8250. (800) 438-4380; (301) 495-3311; FAX (301) 495-3334. PRICE: Free. Order Number Z-144. NIH Publication Number: 98-4013. The full text of this document is also available at http://www.alzheimers.org/pubs/ginkgo.html. Summary: This fact sheet discusses what is known about ginkgo biloba as a potential treatment for Alzheimer's disease (AD). Although findings from a 1997 study at the New York Institute for Medical Research suggest that a ginkgo extract may improve some of the symptoms of AD and vascular dementia, there is currently no evidence that ginkgo biloba will cure or prevent AD. In addition, some recent case studies indicate that daily use of ginkgo biloba may cause side effects such as excessive bleeding, especially in people with blood circulation or clotting disorders and those taking anticoagulants such as aspirin. The fact sheet briefly summarizes the New York study, describes a new study of ginkgo biloba sponsored by the National Institute on Aging and the Office of Alternative Medicine, and discusses some of the factors to consider before using ginkgo extracts.
•
Antiphospholipid Syndrome (APL) Source: Detroit, MI: American Autoimmune Related Diseases Association, Inc. 199x. 2 p. Contact: Available from American Autoimmune Related Diseases Association, Inc. (AARDA). Michigan National Bank Building, 15475 Gratiot Avenue, Detroit, MI 48205. (313) 371-8600. Website: www.aarda.org. PRICE: Single copy free; send self-addressed, stamped envelope. Summary: This fact sheet for people with antiphospholipid (APL) syndrome discusses the affected population, complications, and treatment of this autoimmune syndrome. Although APL antibodies were thought to occur only in patients with lupus, it is now known that they can also constitute a primary syndrome. There is most likely a genetic predisposition , and people most at risk are those with high-titer immunoglobulin G APL antibodies. Patients with these antibodies tend to form blood clots in the legs, brain, and other parts of the body, and they may experience other cardiovascular problems as well. In addition, patients may have false positive test results for syphilis. About 33 percent of patients with lupus have APL antibodies, up to 20 percent of patients with rheumatic arthritis also have them, and 10 to 20 percent of patients with other forms of vasculitis have them as well. The goal of treatment is to prevent problems. Patients with APL antibodies are frequently told to take one baby aspirin a day as a preventive measure. Treatment may also consist of using medications such as antimalarials, blood thinners, or anticoagulants. The fact sheet explains what
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autoimmunity is, lists other common autoimmune diseases, and outlines the activities of the American Autoimmune Related Diseases Association. 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 “anticoagulants” (or synonyms). The following was recently posted: •
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=anticoagulants 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 anticoagulants. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats
•
Family Village: http://www.familyvillage.wisc.edu/specific.htm
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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
•
Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/
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Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/
•
WebMDHealth: http://my.webmd.com/health_topics
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Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to anticoagulants. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with anticoagulants. 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 anticoagulants. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “anticoagulants” (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 “anticoagulants”. 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 “anticoagulants” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months.
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The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “anticoagulants” (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.21
Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.
Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of
21
Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.
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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)22: •
Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/
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Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)
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Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm
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California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html
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California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html
•
California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html
•
California: Gateway Health Library (Sutter Gould Medical Foundation)
•
California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/
•
California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp
•
California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html
•
California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/
•
California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/
•
California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/
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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
•
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/
•
Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/
22
Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.
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•
Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml
•
Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm
•
Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html
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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
•
Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/
•
Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm
•
Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/
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Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/
•
Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/
•
Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm
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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
•
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
•
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
•
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
•
MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp
•
Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/
•
Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html
•
On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/
•
Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp
•
Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm
Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a). The NIH suggests the following Web sites in the ADAM Medical Encyclopedia when searching for information on anticoagulants: •
Basic Guidelines for Anticoagulants Anticoagulant used in rodenticides Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002595.htm
•
Signs & Symptoms for Anticoagulants Blood in the urine Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003138.htm Bruising Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003235.htm Emesis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003117.htm Vomiting Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003117.htm
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Vomiting blood Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003118.htm •
Diagnostics and Tests for Anticoagulants Blood pressure Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003398.htm Pulse Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003399.htm
•
Background Topics for Anticoagulants Bleeding Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000045.htm Vital signs Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002341.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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ANTICOAGULANTS 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] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acetaminophen: Analgesic antipyretic derivative of acetanilide. It has weak antiinflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acetylgalactosamine: The N-acetyl derivative of galactosamine. [NIH] Acetylglucosamine: The N-acetyl derivative of glucosamine. [NIH] Acrosin: A trypsin-like enzyme of spermatozoa which is not inhibited by alpha 1 antitrypsin. [NIH] Acute renal: A condition in which the kidneys suddenly stop working. In most cases, kidneys can recover from almost complete loss of function. [NIH] Acylation: The addition of an organic acid radical into a molecule. [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] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adhesives: Substances that cause the adherence of two surfaces. They include glues (properly collagen-derived adhesives), mucilages, sticky pastes, gums, resins, or latex. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with
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similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adverse Effect: An unwanted side effect of treatment. [NIH] 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] Affinity Chromatography: In affinity chromatography, a ligand attached to a column binds specifically to the molecule to be purified. [NIH] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]
Alanine: A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases immunity, and provides energy for muscle tissue, brain, and the central nervous system. [NIH] 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] 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] 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] Aluminum: A metallic element that has the atomic number 13, atomic symbol Al, and atomic weight 26.98. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and
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tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Ampulla: A sac-like enlargement of a canal or duct. [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] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Anesthetics: Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. [NIH] 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] 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 procedures performed by catheterization. When reconstruction of an artery is performed surgically, it is called endarterectomy. [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] Anionic: Pertaining to or containing an anion. [EU] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or
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positive pole during electrolysis. [NIH] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]
Annexins: Family of calcium- and phospholipid-binding proteins which are structurally related and exhibit immunological cross-reactivity. Each member contains four homologous 70 kD repeats. The annexins are differentially distributed in vertebrate tissues (and lower eukaryotes) and appear to be involved in membrane fusion and signal transduction. [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] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]
Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] 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] Anticonvulsant: An agent that prevents or relieves convulsions. [EU] Antidote: A remedy for counteracting a poison. [EU] Antifungal: Destructive to fungi, or suppressing their reproduction or growth; effective against fungal infections. [EU] Antifungal Agents: Substances that destroy fungi by suppressing their ability to grow or reproduce. They differ from fungicides, industrial because they defend against fungi present in human or animal tissues. [NIH] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU]
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Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Anti-inflammatory: Having to do with reducing inflammation. [NIH] 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] Antipyretic: An agent that relieves or reduces fever. Called also antifebrile, antithermic and febrifuge. [EU] Antithrombins: An endogenous family of proteins belonging to the serpin superfamily that neutralizes the action of thrombin. Six naturally occuring antithrombins have been identified and are designated by Roman numerals I to VI. Of these, Antithrombin I and antithrombin III appear to be of major importance. [NIH] Antithrombotic: Preventing or interfering with the formation of thrombi; an agent that so acts. [EU] Antituberculosis: Refers to a drug used to treat tuberculosis. [NIH] Antiviral: Destroying viruses or suppressing their replication. [EU] Aorta: The main trunk of the systemic arteries. [NIH] Apheresis: Components plateletpheresis. [NIH]
being
separated
out,
as
leukapheresis,
plasmapheresis,
Apolipoproteins: The protein components of lipoproteins which remain after the lipids to which the proteins are bound have been removed. They play an important role in lipid transport and metabolism. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Aqueous: Having to do with water. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteriosclerosis: Thickening and loss of elasticity of arterial walls. Atherosclerosis is the
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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] Arteriovenous: Both arterial and venous; pertaining to or affecting an artery and a vein. [EU] Arteriovenous Fistula: An abnormal communication between an artery and a vein. [NIH] 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] Aspergillosis: Infections with fungi of the genus Aspergillus. [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] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] Atenolol: A cardioselective beta-adrenergic blocker possessing properties and potency similar to propranolol, but without a negative inotropic effect. [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] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Attenuated: Strain with weakened or reduced virulence. [NIH] Auricular: Pertaining to an auricle or to the ear, and, formerly, to an atrium of the heart. [EU] Autoantibodies: Antibodies that react with self-antigens (autoantigens) of the organism that produced them. [NIH] Autoantigens: Endogenous tissue constituents that have the ability to interact with autoantibodies and cause an immune response. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign
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and directs an immune response against them. [NIH] Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by autoimmune diseases. [NIH] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] Benzodiazepines: A two-ring heterocyclic compound consisting of a benzene ring fused to a diazepine ring. Permitted is any degree of hydrogenation, any substituents and any Hisomer. [NIH] Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bile Acids and Salts: Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones. [NIH] Bile duct: A tube through which bile passes in and out of the liver. [NIH] Bile Pigments: Pigments that give a characteristic color to bile including: bilirubin, biliverdine, and bilicyanin. [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] 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] Biochemical reactions: In living cells, chemical reactions that help sustain life and allow cells to grow. [NIH] Biocompatible Materials: Synthetic or natural materials, other than drugs, that are used to replace or repair any body tissue or bodily function. [NIH] Biological response modifier: BRM. A substance that stimulates the body's response to
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infection and disease. [NIH] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biological Transport: The movement of materials (including biochemical substances and drugs) across cell membranes and epithelial layers, usually by passive diffusion. [NIH] Biopolymers: Polymers, such as proteins, DNA, RNA, or polysaccharides formed by any living organism. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Bivalent: Pertaining to a group of 2 homologous or partly homologous chromosomes during the zygotene stage of prophase to the first metaphase in meiosis. [NIH] Bladder: The organ that stores urine. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Coagulation Factors: Endogenous substances, usually proteins, that are involved in the blood coagulation process. [NIH] Blood Coagulation Tests: Laboratory tests for evaluating the individual's clotting mechanism. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blood-Brain Barrier: Specialized non-fenestrated tightly-joined endothelial cells (tight junctions) that form a transport barrier for certain substances between the cerebral capillaries and the brain tissue. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Bone Density: The amount of mineral per square centimeter of bone. This is the definition used in clinical practice. Actual bone density would be expressed in grams per milliliter. It is most frequently measured by photon absorptiometry or x-ray computed tomography. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and
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is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone Marrow Transplantation: The transference of bone marrow from one human or animal to another. [NIH] Brachial: All the nerves from the arm are ripped from the spinal cord. [NIH] Brachial Artery: The continuation of the axillary artery; it branches into the radial and ulnar arteries. [NIH] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH] Bradycardia: Excessive slowness in the action of the heart, usually with a heart rate below 60 beats per minute. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Brain Hypoxia: Lack of oxygen leading to unconsciousness. [NIH] Brain Infarction: The formation of an area of necrosis in the brain, including the cerebral hemispheres (cerebral infarction), thalami, basal ganglia, brain stem (brain stem infarctions), or cerebellum secondary to an insufficiency of arterial or venous blood flow. [NIH] Brain Ischemia: Localized reduction of blood flow to brain tissue due to arterial obtruction or systemic hypoperfusion. This frequently occurs in conjuction with brain hypoxia. Prolonged ischemia is associated with brain infarction. [NIH] Brain Stem: The part of the brain that connects the cerebral hemispheres with the spinal cord. It consists of the mesencephalon, pons, and medulla oblongata. [NIH] Brain Stem Infarctions: Infarctions that occur in the brain stem which is comprised of the midbrain, pons, and medulla. There are several named syndromes characterized by their distinctive clinical manifestations and specific sites of ischemic injury. [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] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Bypass: A surgical procedure in which the doctor creates a new pathway for the flow of body fluids. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calcium Chloride: A salt used to replenish calcium levels, as an acid-producing diuretic, and as an antidote for magnesium poisoning. [NIH] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH]
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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] Carboxypeptidases: Enzymes that act at a free C-terminus of a polypeptide to liberate a single amino acid residue. They are further divided based on their catalytic mechanism into serine-type carboxypeptidases EC 3.4.16; metallocarboxypeptidases, EC 3.4.17; and cysteinetype carboxypeptidases, EC 3.4.18. EC 3.4.-. [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] 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] Cardiorespiratory: Relating to the heart and lungs and their function. [EU] Cardioselective: Having greater activity on heart tissue than on other tissue. [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] Cardioversion: Electrical reversion of cardiac arrhythmias to normal sinus rhythm, formerly using alternatic current, but now employing direct current. [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] Cataract: An opacity, partial or complete, of one or both eyes, on or in the lens or capsule, especially an opacity impairing vision or causing blindness. The many kinds of cataract are classified by their morphology (size, shape, location) or etiology (cause and time of occurrence). [EU] 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] Cathode: An electrode, usually an incandescent filament of tungsten, which emits electrons in an X-ray tube. [NIH] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH]
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Cauda Equina: The lower part of the spinal cord consisting of the lumbar, sacral, and coccygeal nerve roots. [NIH] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] Cavernous Sinus: An irregularly shaped venous space in the dura mater at either side of the sphenoid bone. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Division: The fission of a cell. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell Size: The physical dimensions of a cell. It refers mainly to changes in dimensions correlated with physiological or pathological changes in cells. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebellum: Part of the metencephalon that lies in the posterior cranial fossa behind the brain stem. It is concerned with the coordination of movement. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Arteries: The arteries supplying the cerebral cortex. [NIH] Cerebral hemispheres: The two halves of the cerebrum, the part of the brain that controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. The right hemisphere controls muscle movement on the left side of the body, and the left hemisphere controls muscle movement on the right side of the body. [NIH] Cerebral Infarction: The formation of an area of necrosis in the cerebrum caused by an insufficiency of arterial or venous blood flow. Infarcts of the cerebrum are generally classified by hemisphere (i.e., left vs. right), lobe (e.g., frontal lobe infarction), arterial distribution (e.g., infarction, anterior cerebral artery), and etiology (e.g., embolic infarction). [NIH]
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] Chelating Agents: Organic chemicals that form two or more coordination bonds with a central metal ion. Heterocyclic rings are formed with the central metal atom as part of the ring. Some biological systems form metal chelates, e.g., the iron-binding porphyrin group of hemoglobin and the magnesium-binding chlorophyll of plants. (From Hawley's Condensed Chemical Dictionary, 12th ed) They are used chemically to remove ions from solutions, medicinally against microorganisms, to treat metal poisoning, and in chemotherapy
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protocols. [NIH] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chemotherapeutic agent: A drug used to treat cancer. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chin: The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. [NIH] Chlorophyll: Porphyrin derivatives containing magnesium that act to convert light energy in photosynthetic organisms. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Cholesterol Esters: Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a characteristic feature of atherosclerosis. [NIH] Chondroitin sulfate: The major glycosaminoglycan (a type of sugar molecule) in cartilage. [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] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chylomicrons: A class of lipoproteins that carry dietary cholesterol and triglycerides from the small intestines to the tissues. [NIH] Chymotrypsin: A serine endopeptidase secreted by the pancreas as its zymogen, chymotrypsinogen and carried in the pancreatic juice to the duodenum where it is activated by trypsin. It selectively cleaves aromatic amino acids on the carboxyl side. [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] Clarithromycin: A semisynthetic macrolide antibiotic derived from erythromycin that is active against a variety of microorganisms. It can inhibit protein synthesis in bacteria by reversibly binding to the 50S ribosomal subunits. This inhibits the translocation of aminoacyl transfer-RNA and prevents peptide chain elongation. [NIH] Clear cell carcinoma: A rare type of tumor of the female genital tract in which the inside of the cells looks clear when viewed under a microscope. [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] Cloning: The production of a number of genetically identical individuals; in genetic
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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] Coagulants: Exogenous substances used to promote blood coagulation. The endogenous blood coagulation factors are considered to be coagulants only when administered as drugs. [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] Cognition: Intellectual or mental process whereby an organism becomes aware of or obtains knowledge. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collagen disease: A term previously used to describe chronic diseases of the connective tissue (e.g., rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis), but now is thought to be more appropriate for diseases associated with defects in collagen, which is a component of the connective tissue. [NIH] 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] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [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] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] 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] Concomitant: Accompanying; accessory; joined with another. [EU] Congestion: Excessive or abnormal accumulation of blood in a part. [EU] Congestive heart failure: Weakness of the heart muscle that leads to a buildup of fluid in body tissues. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] 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] Consultation: A deliberation between two or more physicians concerning the diagnosis and the proper method of treatment in a case. [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]
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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] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]
Convulsions: A general term referring to sudden and often violent motor activity of cerebral or brainstem origin. Convulsions may also occur in the absence of an electrical cerebral discharge (e.g., in response to hypotension). [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Corneal Ulcer: Loss of epithelial tissue from the surface of the cornea due to progressive erosion and necrosis of the tissue; usually caused by bacterial, fungal, or viral infection. [NIH] Corneum: The superficial layer of the epidermis containing keratinized cells. [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 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] Corpus: The body of the uterus. [NIH] Corpus Luteum: The yellow glandular mass formed in the ovary by an ovarian follicle that has ruptured and discharged its ovum. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Corticosteroids: Hormones that have antitumor activity in lymphomas and lymphoid leukemias; in addition, corticosteroids (steroids) may be used for hormone replacement and for the management of some of the complications of cancer and its treatment. [NIH] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Coumarin: A fluorescent dye. [NIH] Critical Care: Health care provided to a critically ill patient during a medical emergency or crisis. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical
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compounds that contain a ring of atoms in the nucleus. [EU] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cysteinyl: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] 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] Data Collection: Systematic gathering of data for a particular purpose from various sources, including questionnaires, interviews, observation, existing records, and electronic devices. The process is usually preliminary to statistical analysis of the data. [NIH] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Denaturation: Rupture of the hydrogen bonds by heating a DNA solution and then cooling it rapidly causes the two complementary strands to separate. [NIH] Dental Care: The total of dental diagnostic, preventive, and restorative services provided to meet the needs of a patient (from Illustrated Dictionary of Dentistry, 1982). [NIH] Dentists: Individuals licensed to practice dentistry. [NIH] Dermatitis: Any inflammation of the skin. [NIH] Dermatology: A medical specialty concerned with the skin, its structure, functions, diseases, and treatment. [NIH] DES: Diethylstilbestrol. A synthetic hormone that was prescribed from the early 1940s until 1971 to help women with complications of pregnancy. DES has been linked to an increased
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risk of clear cell carcinoma of the vagina in daughters of women who used DES. DES may also increase the risk of breast cancer in women who used DES. [NIH] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Developed Countries: Countries that have reached a level of economic achievement through an increase of production, per capita income and consumption, and utilization of natural and human resources. [NIH] Diagnostic Errors: Incorrect diagnoses after clinical examination or technical diagnostic procedures. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Dialysate: A cleansing liquid used in the two major forms of dialysis--hemodialysis and peritoneal dialysis. [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] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Dilation: A process by which the pupil is temporarily enlarged with special eye drops (mydriatic); allows the eye care specialist to better view the inside of the eye. [NIH] Dilator: A device used to stretch or enlarge an opening. [NIH] 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] Dipyridamole: A drug that prevents blood cell clumping and enhances the effectiveness of fluorouracil and other chemotherapeutic agents. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discoid: Shaped like a disk. [EU] Discrete: Made up of separate parts or characterized by lesions which do not become blended; not running together; separate. [NIH] Disposition: A tendency either physical or mental toward certain diseases. [EU] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU]
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Diuresis: Increased excretion of urine. [EU] Diuretic: A drug that increases the production of urine. [NIH] Diverticula: Plural form of diverticulum. [NIH] Diverticulitis: Inflammation of a diverticulum or diverticula. [NIH] Diverticulosis: A condition marked by small sacs or pouches (diverticula) in the walls of an organ such as the stomach or colon. These sacs can become inflamed and cause a condition called diverticulitis, which may be a risk factor for certain types of cancer. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dose-dependent: Refers to the effects of treatment with a drug. If the effects change when the dose of the drug is changed, the effects are said to be dose dependent. [NIH] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Drug Combinations: Single preparations containing two or more active agents, for the purpose of their concurrent administration as a fixed dose mixture. It is differentiated from combination drug therapy in which two or more drugs are administered separately for a combined effect. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Duct: A tube through which body fluids pass. [NIH] Duodenum: The first part of the small intestine. [NIH] Dura mater: The outermost, toughest, and most fibrous of the three membranes (meninges) covering the brain and spinal cord; called also pachymeninx. [EU] 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]
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
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applied by a force. [EU] Elasticity: Resistance and recovery from distortion of shape. [NIH] Elastin: The protein that gives flexibility to tissues. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electrocoagulation: Electrosurgical procedures used to treat hemorrhage (e.g., bleeding ulcers) and to ablate tumors, mucosal lesions, and refractory arrhythmias. [NIH] Electrolysis: Destruction by passage of a galvanic electric current, as in disintegration of a chemical compound in solution. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] 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] Ellagic Acid: A fused four ring compound occurring free or combined in galls. Isolated from the kino of Eucalyptus maculata Hook and E. Hemipholia F. Muell. Activates Factor XII of the blood clotting system which also causes kinin release; used in research and as a dye. [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 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] Emergency Treatment: First aid or other immediate intervention for accidents or medical conditions requiring immediate care and treatment before definitive medical and surgical management can be procured. [NIH] Emollient: Softening or soothing; called also malactic. [EU] Emphysema: A pathological accumulation of air in tissues or organs. [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] Endocarditis: Exudative and proliferative inflammatory alterations of the endocardium, characterized by the presence of vegetations on the surface of the endocardium or in the
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endocardium itself, and most commonly involving a heart valve, but sometimes affecting the inner lining of the cardiac chambers or the endocardium elsewhere. It may occur as a primary disorder or as a complication of or in association with another disease. [EU] Endocardium: The innermost layer of the heart, comprised of endothelial cells. [NIH] Endocrinology: A subspecialty of internal medicine concerned with the metabolism, physiology, and disorders of the endocrine system. [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] Endoscopy: Endoscopic examination, therapy or surgery performed on interior parts of the body. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium, Lymphatic: Unbroken cellular lining (intima) of the lymph vessels (e.g., the high endothelial lymphatic venules). It is more permeable than vascular endothelium, lacking selective absorption and functioning mainly to remove plasma proteins that have filtered through the capillaries into the tissue spaces. [NIH] Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components from interstitium to lumen; this function has been most intensively studied in the blood capillaries. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxin: Toxin from cell walls of bacteria. [NIH] Enoxaparin: A drug used to prevent blood clots. It belongs to the family of drugs called anticoagulants. [NIH] Enteropeptidase: A specialized proteolytic enzyme secreted by intestinal cells. It converts trypsinogen into its active form trypsin by removing the N-terminal peptide. EC 3.4.21.9. [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] Enzyme-Linked Immunosorbent Assay: An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity;
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the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidemiological: Relating to, or involving epidemiology. [EU] 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] Epigastric: Having to do with the upper middle area of the abdomen. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] 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]
Erythema: Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of causes. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Erythromycin: A bacteriostatic antibiotic substance produced by Streptomyces erythreus. Erythromycin A is considered its major active component. In sensitive organisms, it inhibits protein synthesis by binding to 50S ribosomal subunits. This binding process inhibits peptidyl transferase activity and interferes with translocation of amino acids during translation and assembly of proteins. [NIH] Erythropoietin: Glycoprotein hormone, secreted chiefly by the kidney in the adult and the liver in the fetus, that acts on erythroid stem cells of the bone marrow to stimulate proliferation and differentiation. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]
Estrogen: One of the two female sex hormones. [NIH] Estrogen Replacement Therapy: The use of hormonal agents with estrogen-like activity in postmenopausal or other estrogen-deficient women to alleviate effects of hormone deficiency, such as vasomotor symptoms, dyspareunia, and progressive development of osteoporosis. This may also include the use of progestational agents in combination therapy. [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] Exhaustion: The feeling of weariness of mind and body. [NIH] Exocrine: Secreting outwardly, via a duct. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU]
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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] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extracorporeal: Situated or occurring outside the body. [EU] Extracorporeal Circulation: Diversion of blood flow through a circuit located outside the body but continuous with the bodily circulation. [NIH] Extraction: The process or act of pulling or drawing out. [EU] Extravasation: A discharge or escape, as of blood, from a vessel into the tissues. [EU] Factor X: Storage-stable glycoprotein blood coagulation factor that can be activated to factor Xa by both the intrinsic and extrinsic pathways. A deficiency of factor X, sometimes called Stuart-Prower factor deficiency, may lead to a systemic coagulation disorder. [NIH] Factor Xa: Activated form of factor X that participates in both the intrinsic and extrinsic pathways of blood coagulation. It catalyzes the conversion of prothrombin to thrombin in conjunction with other cofactors. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] 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 Nerve: A nerve originating in the lumbar spinal cord (usually L2 to L4) and traveling through the lumbar plexus to provide motor innervation to extensors of the thigh and sensory innervation to parts of the thigh, lower leg, and foot, and to the hip and knee joints. [NIH] Femoral Neuropathy: Disease involving the femoral nerve. The femoral nerve may be injured by ischemia (e.g., in association with diabetic neuropathies), nerve compression, trauma, collagen diseases, and other disease processes. Clinical features include muscle weakness or paralysis of hip flexion and knee extension, atrophy of the quadriceps muscles, reduced or absent patellar reflex, and impaired sensation over the anterior and medial thigh. [NIH]
Femur: The longest and largest bone of the skeleton, it is situated between the hip and the knee. [NIH]
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Fetal Distress: Adverse or threatening condition of the fetus identified by fetal bradycardia or tachycardia and passage of meconium in vertex presentation. [NIH] Fetal Viability: The potential of the fetus-in-utero to survive after birth. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrillation: A small, local, involuntary contraction of muscle, invisible under the skin, resulting from spontaneous activation of single muscle cells or muscle fibres. [EU] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of 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] Fibronectin: An adhesive glycoprotein. One form circulates in plasma, acting as an opsonin; another is a cell-surface protein which mediates cellular adhesive interactions. [NIH] Filler: An inactive substance used to make a product bigger or easier to handle. For example, fillers are often used to make pills or capsules because the amount of active drug is too small to be handled conveniently. [NIH] Filtration: The passage of a liquid through a filter, accomplished by gravity, pressure, or vacuum (suction). [EU] Flatus: Gas passed through the rectum. [NIH] Flexion: In gynaecology, a displacement of the uterus in which the organ is bent so far forward or backward that an acute angle forms between the fundus and the cervix. [EU] Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake. [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] Fluorescent Dyes: Dyes that emit light when exposed to light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags. They are used as markers in biochemistry and immunology. [NIH] Fluorouracil: A pyrimidine analog that acts as an antineoplastic antimetabolite and also has
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immunosuppressant. It interferes with DNA synthesis by blocking the thymidylate synthetase conversion of deoxyuridylic acid to thymidylic acid. [NIH] Flutter: A rapid vibration or pulsation. [EU] Fold: A plication or doubling of various parts of the body. [NIH] Foramen: A natural hole of perforation, especially one in a bone. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Fossa: A cavity, depression, or pit. [NIH] Free Radicals: Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. [NIH] Fungicides, Industrial: Chemicals that kill or inhibit the growth of fungi in agricultural applications, on wood, plastics, or other materials, in swimming pools, etc. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Ganglion: 1. A knot, or knotlike mass. 2. A general term for a group of nerve cell bodies located outside the central nervous system; occasionally applied to certain nuclear groups within the brain or spinal cord, e.g. basal ganglia. 3. A benign cystic tumour occurring on a aponeurosis or tendon, as in the wrist or dorsum of the foot; it consists of a thin fibrous capsule enclosing a clear mucinous fluid. [EU] 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]
Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Therapy: The introduction of new genes into cells for the purpose of treating disease by restoring or adding gene expression. Techniques include insertion of retroviral vectors, transfection, homologous recombination, and injection of new genes into the nuclei of single cell embryos. The entire gene therapy process may consist of multiple steps. The new genes may be introduced into proliferating cells in vivo (e.g., bone marrow) or in vitro (e.g., fibroblast cultures) and the modified cells transferred to the site where the gene expression is required. Gene therapy may be particularly useful for treating enzyme deficiency diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug sensitivity, particularly for leukemia. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base
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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 testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genital: Pertaining to the genitalia. [EU] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Ginkgo biloba: Exclusive species of the genus Ginkgo, family Ginkgoacea. It produces extracts of medicinal interest. Ginkgo may refer to the genus or species. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]
Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] 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] Glucuronides: Glycosides of glucuronic acid formed by the reaction of uridine diphosphate glucuronic acid with certain endogenous and exogenous substances. Their formation is important for the detoxification of drugs, steroid excretion and bilirubin metabolism to a more water-soluble compound that can be eliminated in the urine and bile. [NIH] Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent. [NIH]
Glycerophospholipids: Derivatives of phosphatidic acid in which the hydrophobic regions are composed of two fatty acids and a polar alcohol is joined to the C-3 position of glycerol through a phosphodiester bond. They are named according to their polar head groups, such as phosphatidylcholine and phosphatidylethanolamine. [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] Glycosaminoglycan: A type of long, unbranched polysaccharide molecule. Glycosaminoglycans are major structural components of cartilage and are also found in the cornea of the eye. [NIH] Glycosidic: Formed by elimination of water between the anomeric hydroxyl of one sugar and a hydroxyl of another sugar molecule. [NIH] Governing Board: The group in which legal authority is vested for the control of health-
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related institutions and organizations. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Grafting: The operation of transfer of tissue from one site to another. [NIH] Gram-negative: Losing the stain or decolorized by alcohol in Gram's method of staining, a primary characteristic of bacteria having a cell wall composed of a thin layer of peptidoglycan covered by an outer membrane of lipoprotein and lipopolysaccharide. [EU] Granule: A small pill made from sucrose. [EU] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Gynecology: A medical-surgical specialty concerned with the physiology and disorders primarily of the female genital tract, as well as female endocrinology and reproductive physiology. [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] Health Services: Services for the diagnosis and treatment of disease and the maintenance of health. [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] Heart Valves: Flaps of tissue that prevent regurgitation of blood from the ventricles to the atria or from the pulmonary arteries or aorta to the ventricles. [NIH] Heartbeat: One complete contraction of the heart. [NIH] Heart-Lung Machine: A mechanical device that temporarily takes over the functions of the heart and lungs; called also a pump-oxygenator. It is used as an aid to surgery. [NIH] Hematology: A subspecialty of internal medicine concerned with morphology, physiology, and pathology of the blood and blood-forming tissues. [NIH] Hematoma: An extravasation of blood localized in an organ, space, or tissue. [NIH] Hemodiafiltration: The combination of hemodialysis and hemofiltration either simultaneously or sequentially. Convective transport (hemofiltration) may be better for removal of larger molecular weight substances and diffusive transport (hemodialysis) for smaller molecular weight solutes. [NIH] Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH] Hemofiltration: Extracorporeal ultrafiltration technique without hemodialysis for treatment of fluid overload and electrolyte disturbances affecting renal, cardiac, or pulmonary function. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to
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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] Hemoglobin A: Normal adult human hemoglobin. The globin moiety consists of two alpha and two beta chains. [NIH] Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. [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] 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] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Heritability: The proportion of observed variation in a particular trait that can be attributed to inherited genetic factors in contrast to environmental ones. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]
Hirudin: The active principle in the buccal gland secretion of leeches. It acts as an antithrombin and as an antithrombotic agent. [NIH] Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird
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and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Horny layer: The superficial layer of the epidermis containing keratinized cells. [NIH] Horseradish Peroxidase: An enzyme isolated from horseradish which is able to act as an antigen. It is frequently used as a histochemical tracer for light and electron microscopy. Its antigenicity has permitted its use as a combined antigen and marker in experimental immunology. [NIH] 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] Hydrochloric Acid: A strong corrosive acid that is commonly used as a laboratory reagent. It is formed by dissolving hydrogen chloride in water. Gastric acid is the hydrochloric acid component of gastric juice. [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 Bonding: A low-energy attractive force between hydrogen and another element. It plays a major role in determining the properties of water, proteins, and other compounds. [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] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] 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] Hyperbilirubinemia: Pathologic process consisting of an abnormal increase in the amount of bilirubin in the circulating blood, which may result in jaundice. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Iduronic Acid: Component of dermatan sulfate. Differs in configuration from glucuronic acid only at the C-5 position. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]
Immune system: The organs, cells, and molecules responsible for the recognition and
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disposal of foreign ("non-self") material which enters the body. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]
effects
of
foreign
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] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulins: Glycoproteins present in the blood (antibodies) and in other tissue. They are classified by structure and activity into five classes (IgA, IgD, IgE, IgG, IgM). [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunologic Tests: Diagnostic techniques involving the demonstration or measurement of an immune response, including antibody production or assay, antigen-antibody reactions, serologic cross-reactivity, delayed hypersensitivity reactions, or heterogenetic responses. [NIH]
Immunology: The study of the body's immune system. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] Impotence: The inability to perform sexual intercourse. [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus,
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or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]
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] Infertility: The diminished or absent ability to conceive or produce an offspring while sterility is the complete inability to conceive or produce an offspring. [NIH] Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [EU] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Initiator: A chemically reactive substance which may cause cell changes if ingested, inhaled or absorbed into the body; the substance may thus initiate a carcinogenic process. [NIH] Inotropic: Affecting the force or energy of muscular contractions. [EU] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Intensive Care: Advanced and highly specialized care provided to medical or surgical patients whose conditions are life-threatening and require comprehensive care and constant monitoring. It is usually administered in specially equipped units of a health care facility. [NIH]
Intensive Care Units: Hospital units providing continuous surveillance and care to acutely ill patients. [NIH] Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH]
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Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Interleukin-1: A soluble factor produced by monocytes, macrophages, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. IL-1 consists of two distinct forms, IL-1 alpha and IL-1 beta which perform the same functions but are distinct proteins. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. The factor is distinct from interleukin-2. [NIH] Interleukin-10: Factor that is a coregulator of mast cell growth. It is produced by T-cells and B-cells and shows extensive homology with the Epstein-Barr virus BCRFI gene. [NIH] Interleukin-2: Chemical mediator produced by activated T lymphocytes and which regulates the proliferation of T cells, as well as playing a role in the regulation of NK cell activity. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Intermittent Claudication: A symptom complex characterized by leg pain and weakness brought on by walking, with the disappearance of the symptoms following a brief rest. [NIH] 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] International Normalized Ratio: System established by the World Health Organization and the International Committee on Thrombosis and Hemostasis for monitoring and reporting blood coagulation tests. Under this system, results are standardized using the International Sensitivity Index for the particular test reagent/instrument combination used. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] Intestines: The section of the alimentary canal from the stomach to the anus. It includes the large intestine and small intestine. [NIH] Intracellular: Inside a cell. [NIH] Intravascular: Within a vessel or vessels. [EU] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]
Invertebrates: Animals that have no spinal column. [NIH] Involuntary: Reaction occurring without intention or volition. [NIH] Ionization: 1. Any process by which a neutral atom gains or loses electrons, thus acquiring a net charge, as the dissociation of a substance in solution into ions or ion production by the passage of radioactive particles. 2. Iontophoresis. [EU] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH]
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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] Isotonic: A biological term denoting a solution in which body cells can be bathed without a net flow of water across the semipermeable cell membrane. Also, denoting a solution having the same tonicity as some other solution with which it is compared, such as physiologic salt solution and the blood serum. [EU] Jaundice: A clinical manifestation of hyperbilirubinemia, consisting of deposition of bile pigments in the skin, resulting in a yellowish staining of the skin and mucous membranes. [NIH]
Kallikreins: Proteolytic enzymes from the serine endopeptidase family found in normal blood and urine. Specifically, Kallikreins are potent vasodilators and hypotensives and increases vascular permeability and affects smooth muscle. They act as infertility agents in men. Three forms are recognized, plasma kallikrein (EC 3.4.21.34), tissue kallikrein (EC 3.4.21.35), and prostate-specific antigen (EC 3.4.21.77). [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] Kinetic: Pertaining to or producing motion. [EU] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Laminin: Large, noncollagenous glycoprotein with antigenic properties. It is localized in the basement membrane lamina lucida and functions to bind epithelial cells to the basement membrane. Evidence suggests that the protein plays a role in tumor invasion. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] Leukapheresis: The preparation of leukocyte concentrates with the return of red cells and leukocyte-poor plasma to the donor. [NIH] Leukemia: Cancer of blood-forming tissue. [NIH] Life cycle: The successive stages through which an organism passes from fertilized ovum or
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spore to the fertilized ovum or spore of the next generation. [NIH] Life Expectancy: A figure representing the number of years, based on known statistics, to which any person of a given age may reasonably expect to live. [NIH] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Ligands: A RNA simulation method developed by the MIT. [NIH] Linkages: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lipid: Fat. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipophilic: Having an affinity for fat; pertaining to or characterized by lipophilia. [EU] Lipopolysaccharide: Substance consisting of polysaccaride and lipid. [NIH] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Loc: A brain region associated with object recognition. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Locoregional: The characteristic of a disease-producing organism to transfer itself, but typically to the same region of the body (a leg, the lungs, .) [EU] 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] Low-density lipoprotein: Lipoprotein that contains most of the cholesterol in the blood. LDL carries cholesterol to the tissues of the body, including the arteries. A high level of LDL increases the risk of heart disease. LDL typically contains 60 to 70 percent of the total serum cholesterol and both are directly correlated with CHD risk. [NIH] Lucida: An instrument, invented by Wollaton, consisting essentially of a prism or a mirror through which an object can be viewed so as to appear on a plane surface seen in direct view and on which the outline of the object may be traced. [NIH] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [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]
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Lymphocytes: White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each); those with characteristics of neither major class are called null cells. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lysine: An essential amino acid. It is often added to animal feed. [NIH] Lytic: 1. Pertaining to lysis or to a lysin. 2. Producing lysis. [EU] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] 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] Malignant tumor: A tumor capable of metastasizing. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]
Malondialdehyde: The dialdehyde of malonic acid. [NIH] Mammary: Pertaining to the mamma, or breast. [EU] Mandible: The largest and strongest bone of the face constituting the lower jaw. It supports the lower teeth. [NIH] 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, 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] Meat: The edible portions of any animal used for food including domestic mammals (the major ones being cattle, swine, and sheep) along with poultry, fish, shellfish, and game. [NIH]
Meconium: The thick green-to-black mucilaginous material found in the intestines of a fullterm fetus. It consists of secretions of the intestinal glands, bile pigments, fatty acids, amniotic fluid, and intrauterine debris. It constitutes the first stools passed by a newborn. [NIH]
Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Medical Errors: Errors or mistakes committed by health professionals which result in harm to the patient. They include errors in diagnosis (diagnostic errors), errors in the
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administration of drugs and other medications (medication errors), errors in the performance of surgical procedures, in the use of other types of therapy, in the use of equipment, and in the interpretation of laboratory findings. Medical errors are differentiated from malpractice in that the former are regarded as honest mistakes or accidents while the latter is the result of negligence, reprehensible ignorance, or criminal intent. [NIH] Medical Records: Recording of pertinent information concerning patient's illness or illnesses. [NIH] Medication Errors: Errors in prescribing, dispensing, or administering medication with the result that the patient fails to receive the correct drug or the indicated proper drug dosage. [NIH]
MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Fusion: The adherence of cell membranes, intracellular membranes, or artifical membrane models of either to each other or to viruses, parasites, or interstitial particles through a variety of chemical and physical processes. [NIH] Membrane Lipids: Lipids, predominantly phospholipids, cholesterol and small amounts of glycolipids found in membranes including cellular and intracellular membranes. These lipids may be arranged in bilayers in the membranes with integral proteins between the layers and peripheral proteins attached to the outside. Membrane lipids are required for active transport, several enzymatic activities and membrane formation. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Menstrual Cycle: The period of the regularly recurring physiologic changes in the endometrium occurring during the reproductive period in human females and some primates and culminating in partial sloughing of the endometrium (menstruation). [NIH] 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 Processes: Conceptual functions or thinking in all its forms. [NIH] Mercury: A silver metallic element that exists as a liquid at room temperature. It has the atomic symbol Hg (from hydrargyrum, liquid silver), atomic number 80, and atomic weight 200.59. Mercury is used in many industrial applications and its salts have been employed therapeutically as purgatives, antisyphilitics, disinfectants, and astringents. It can be absorbed through the skin and mucous membranes which leads to mercury poisoning.
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Because of its toxicity, the clinical use of mercury and mercurials is diminishing. [NIH] Meta-Analysis: A quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with application chiefly in the areas of research and medicine. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metaphase: The second phase of cell division, in which the chromosomes line up across the equatorial plane of the spindle prior to separation. [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] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microglia: The third type of glial cell, along with astrocytes and oligodendrocytes (which together form the macroglia). Microglia vary in appearance depending on developmental stage, functional state, and anatomical location; subtype terms include ramified, perivascular, ameboid, resting, and activated. Microglia clearly are capable of phagocytosis and play an important role in a wide spectrum of neuropathologies. They have also been suggested to act in several other roles including in secretion (e.g., of cytokines and neural growth factors), in immunological processing (e.g., antigen presentation), and in central nervous system development and remodeling. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Middle Cerebral Artery: The largest and most complex of the cerebral arteries. Branches of the middle cerebral artery supply the insular region, motor and premotor areas, and large regions of the association cortex. [NIH] Milliliter: A measure of volume for a liquid. A milliliter is approximately 950-times smaller than a quart and 30-times smaller than a fluid ounce. A milliliter of liquid and a cubic centimeter (cc) of liquid are the same. [NIH] Miscarriage: Spontaneous expulsion of the products of pregnancy before the middle of the second trimester. [NIH] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mitral Valve: The valve between the left atrium and left ventricle of the heart. [NIH] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired
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from its own activity or environment. [NIH] Modulator: A specific inductor that brings out characteristics peculiar to a definite region. [EU]
Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecular mass: The sum of the atomic masses of all atoms in a molecule, based on a scale in which the atomic masses of hydrogen, carbon, nitrogen, and oxygen are 1, 12, 14, and 16, respectively. For example, the molecular mass of water, which has two atoms of hydrogen and one atom of oxygen, is 18 (i.e., 2 + 16). [NIH] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoamine: Enzyme that breaks down dopamine in the astrocytes and microglia. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monoclonal antibodies: Laboratory-produced substances that can locate and bind to cancer cells wherever they are in the body. Many monoclonal antibodies are used in cancer detection or therapy; each one recognizes a different protein on certain cancer cells. Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to a tumor. [NIH] Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. [NIH] Mononuclear: A cell with one nucleus. [NIH] Morphological: Relating to the configuration or the structure of live organs. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucociliary: Pertaining to or affecting the mucus membrane and hairs (including eyelashes, nose hair, .): mucociliary clearing: the clearance of mucus by ciliary movement ( particularly in the respiratory system). [EU] Mucosa: A mucous membrane, or tunica mucosa. [EU] Multiple Myeloma: A malignant tumor of plasma cells usually arising in the bone marrow; characterized by diffuse involvement of the skeletal system, hyperglobulinemia, Bence-Jones proteinuria, and anemia. [NIH] Multiple Organ Failure: A progressive condition usually characterized by combined failure of several organs such as the lungs, liver, kidney, along with some clotting mechanisms, usually postinjury or postoperative. [NIH] Muscle relaxant: An agent that specifically aids in reducing muscle tension, as those acting at the polysynaptic neurons of motor nerves (e.g. meprobamate) or at the myoneural junction (curare and related compounds). [EU] Muscle Spindles: Mechanoreceptors found between skeletal muscle fibers. Muscle spindles
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are arranged in parallel with muscle fibers and respond to the passive stretch of the muscle, but cease to discharge if the muscle contracts isotonically, thus signaling muscle length. The muscle spindles are the receptors responsible for the stretch or myotactic reflex. [NIH] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. [NIH] Myeloma: Cancer that arises in plasma cells, a type of white blood cell. [NIH] Myeloproliferative Disorders: Disorders in which one or more stimuli cause proliferation of hemopoietically active tissue or of tissue which has embryonic hemopoietic potential. [NIH] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neoplasm: A new growth of benign or malignant tissue. [NIH] Nephritis: Inflammation of the kidney; a focal or diffuse proliferative or destructive process which may involve the glomerulus, tubule, or interstitial renal tissue. [EU] Nephrology: A subspecialty of internal medicine concerned with the anatomy, physiology, and pathology of the kidney. [NIH] Nephrotoxic: Toxic or destructive to kidney cells. [EU] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Neurologic: Having to do with nerves or the nervous system. [NIH] Neurology: A medical specialty concerned with the study of the structures, functions, and diseases of the nervous system. [NIH] Neuropathy: A problem in any part of the nervous system except the brain and spinal cord. Neuropathies can be caused by infection, toxic substances, or disease. [NIH] Neurosurgery: A surgical specialty concerned with the treatment of diseases and disorders of the brain, spinal cord, and peripheral and sympathetic nervous system. [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]
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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 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] Nitroglycerin: A highly volatile organic nitrate that acts as a dilator of arterial and venous smooth muscle and is used in the treatment of angina. It provides relief through improvement of the balance between myocardial oxygen supply and demand. Although total coronary blood flow is not increased, there is redistribution of blood flow in the heart when partial occlusion of coronary circulation is effected. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nursing Care: Care given to patients by nursing service personnel. [NIH] Obstetrics: A medical-surgical specialty concerned with management and care of women during pregnancy, parturition, and the puerperium. [NIH] Occupational Medicine: Medical specialty concerned with the promotion and maintenance of the physical and mental health of employees in occupational settings. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Ophthalmic: Pertaining to the eye. [EU] Oral Surgical Procedures: Procedures used to treat disease, injuries, and defects of the oral and maxillofacial region. [NIH] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH]
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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] Ovarian Follicle: Spheroidal cell aggregation in the ovary containing an ovum. It consists of an external fibro-vascular coat, an internal coat of nucleated cells, and a transparent, albuminous fluid in which the ovum is suspended. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]
Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Oximetry: The determination of oxygen-hemoglobin saturation of blood either by withdrawing a sample and passing it through a classical photoelectric oximeter or by electrodes attached to some translucent part of the body like finger, earlobe, or skin fold. It includes non-invasive oxygen monitoring by pulse oximetry. [NIH] Oxygenation: The process of supplying, treating, or mixing with oxygen. No:1245 oxygenation the process of supplying, treating, or mixing with oxygen. [EU] Oxygenator: An apparatus by which oxygen is introduced into the blood during circulation outside the body, as during open heart surgery. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic Juice: The fluid containing digestive enzymes secreted by the pancreas in response to food in the duodenum. [NIH] Paralysis: Loss of ability to move all or part of the body. [NIH] Paranasal Sinuses: Air-filled extensions of the respiratory part of the nasal cavity into the frontal, ethmoid, sphenoid, and maxillary cranial bones. They vary in size and form in different individuals and are lined by the ciliated mucous membranes of the nasal cavity. [NIH]
Paresthesia: Subjective cutaneous sensations (e.g., cold, warmth, tingling, pressure, etc.) that are experienced spontaneously in the absence of stimulation. [NIH] Partial Thromboplastin Time: Test of the intrinsic (factors VIII, IX, XI, and XII) and
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common (fibrinogen, prothrombin, factors V and X) pathways of coagulation in which a mixture of plasma and phospholipid platelet substitute (e.g., crude cephalins, soybean phosphatides) is recalcified and the time required for the appearance of fibrin strands measured. Activation may be provided by contact with the glass tube or exposure to activators (e.g., ellagic acid, particulate silicates such as diatomaceous earth or kaolin) before addition of the calcium chloride. It is used as a screening test and to monitor heparin therapy. [NIH] Parturition: The act or process of given birth to a child. [EU] Pathogen: Any disease-producing microorganism. [EU] 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] Patient Care Management: Generating, planning, organizing, and administering medical and nursing care and services for patients. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]
Patient Selection: Criteria and standards used for the determination of the appropriateness of the inclusion of patients with specific conditions in proposed treatment plans and the criteria used for the inclusion of subjects in various clinical trials and other research protocols. [NIH] Pelvic: Pertaining to the pelvis. [EU] Pelvis: The lower part of the abdomen, located between the hip bones. [NIH] Penicillin: An antibiotic drug used to treat infection. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Peptide Chain Elongation: The process whereby an amino acid is joined through a substituted amide linkage to a chain of peptides. [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] Pericardium: The fibroserous sac surrounding the heart and the roots of the great vessels. [NIH]
Perineal: Pertaining to the perineum. [EU] 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 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
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that heal slowly. Although people with diabetes cannot always avoid PVD, doctors say they have a better chance of avoiding it if they take good care of their feet, do not smoke, and keep both their blood pressure and diabetes under good control. [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Dialysis: Dialysis fluid being introduced into and removed from the peritoneal cavity as either a continuous or an intermittent procedure. [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] Pharmacodynamics: The study of the biochemical and physiological effects of drugs and the mechanisms of their actions, including the correlation of actions and effects of drugs with their chemical structure; also, such effects on the actions of a particular drug or drugs. [EU] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Phenprocoumon: 3-(1-Phenylpropyl)-4-hydroxycoumarin. Long acting oral anticoagulant. It may cause diarrhea. [NIH] Phenytoin: An anticonvulsant that is used in a wide variety of seizures. It is also an antiarrhythmic and a muscle relaxant. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, active transport, and general membrane stabilization. The mechanism of its muscle relaxant effect appears to involve a reduction in the sensitivity of muscle spindles to stretch. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] 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 "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]
Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other
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nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma Kallikrein: A peptidohydrolytic enzyme that is formed from prekallikrein by factor XIIA. It activates factor XII, factor VII, and plasminogen. It is selective for both arginine and to a lesser extent lysinebonds. EC 3.4.21.34. [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] Plasmapheresis: Procedure whereby plasma is separated and extracted from anticoagulated whole blood and the red cells retransfused to the donor. Plasmapheresis is also employed for therapeutic use. [NIH] Plasmin: A product of the lysis of plasminogen (profibrinolysin) by plasminogen activators. It is composed of two polypeptide chains, light (B) and heavy (A), with a molecular weight of 75,000. It is the major proteolytic enzyme involved in blood clot retraction or the lysis of fibrin and quickly inactivated by antiplasmins. EC 3.4.21.7. [NIH] Plasminogen 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] Platelet Aggregation Inhibitors: Drugs or agents which antagonize or impair any mechanism leading to blood platelet aggregation, whether during the phases of activation and shape change or following the dense-granule release reaction and stimulation of the prostaglandin-thromboxane system. [NIH] Platelet Factor 3: A lipoprotein with pronounced electronegative surface charge found in association with platelet membrane and platelet granules. In the sequence of blood coagulation reactions, it is required for activation of factor VIII and for the conversion of prothrombin to thrombin. [NIH] Plateletpheresis: The preparation of platelet concentrates with the return of red cells and
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platelet-poor plasma to the donor. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Pneumonia: Inflammation of the lungs. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. [NIH] Polymers: Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., polypeptides, proteins, plastics). [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postoperative: After surgery. [NIH] 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] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potentiates: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis,
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therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Preeclampsia: A toxaemia of late pregnancy characterized by hypertension, edema, and proteinuria, when convulsions and coma are associated, it is called eclampsia. [EU] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Primary Prevention: Prevention of disease or mental disorders in susceptible individuals or populations through promotion of health, including mental health, and specific protection, as in immunization, as distinguished from the prevention of complications or after-effects of existing disease. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Prodrug: A substance that gives rise to a pharmacologically active metabolite, although not itself active (i. e. an inactive precursor). [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Propranolol: A widely used non-cardioselective beta-adrenergic antagonist. Propranolol is used in the treatment or prevention of many disorders including acute myocardial infarction, arrhythmias, angina pectoris, hypertension, hypertensive emergencies, hyperthyroidism, migraine, pheochromocytoma, menopause, and anxiety. [NIH] 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]
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Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond (5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane). The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also). The effect produced by the cyclic AMP increase depends on the specific cell type. In some cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Prostatectomy: Complete or partial surgical removal of the prostate. Three primary approaches are commonly employed: suprapubic - removal through an incision above the pubis and through the urinary bladder; retropubic - as for suprapubic but without entering the urinary bladder; and transurethral (transurethral resection of prostate). [NIH] Prostate-Specific Antigen: Kallikrein-like serine proteinase produced by epithelial cells of both benign and malignant prostate tissue. It is an important marker for the diagnosis of prostate cancer. EC 3.4.21.77. [NIH] Prosthesis: An artificial replacement of a part of the body. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protease Inhibitors: Compounds which inhibit or antagonize biosynthesis or actions of proteases (endopeptidases). [NIH] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not working properly. [NIH] 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
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thrombin by a prothrombin activator complex consisting of factor Xa, factor V, phospholipid, and calcium ions. Deficiency of prothrombin leads to hypoprothrombinemia. [NIH]
Prothrombin Time: Measurement of clotting time of plasma recalcified in the presence of excess tissue thromboplastin. Factors measured are fibrinogen, prothrombin, and factors V, VII, and X. It is used for monitoring anticoagulant therapy with coumarins. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Pterygoid: A canal in the sphenoid bone for the vidian nerve. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]
Puerperium: Period from delivery of the placenta until return of the reproductive organs to their normal nonpregnant morphologic state. In humans, the puerperium generally lasts for six to eight weeks. [NIH] Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary Circulation: The circulation of blood through the lungs. [NIH] Pulmonary Embolism: Embolism in the pulmonary artery or one of its branches. [NIH] Pulmonary Valve: A valve situated at the entrance to the pulmonary trunk from the right ventricle. [NIH] Pulsation: A throb or rhythmical beat, as of the heart. [EU] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]
Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Putrefaction: The process of decomposition of animal and vegetable matter by living organisms. [NIH] Pyrimidines: A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (cytosine, thymine, and uracil) and form the basic structure of the barbiturates. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH]
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Radial Artery: The direct continuation of the brachial trunk, originating at the bifurcation of the brachial artery opposite the neck of the radius. Its branches may be divided into three groups corresponding to the three regions in which the vessel is situated, the forearm, wrist, and hand. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radical prostatectomy: Surgery to remove the entire prostate. The two types of radical prostatectomy are retropubic prostatectomy and perineal prostatectomy. [NIH] Radioactive: Giving off radiation. [NIH] Radioimmunoassay: Classic quantitative assay for detection of antigen-antibody reactions using a radioactively labeled substance (radioligand) either directly or indirectly to measure the binding of the unlabeled substance to a specific antibody or other receptor system. Nonimmunogenic substances (e.g., haptens) can be measured if coupled to larger carrier proteins (e.g., bovine gamma-globulin or human serum albumin) capable of inducing antibody formation. [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] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Randomized clinical trial: A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial. [NIH] Reaction Time: The time from the onset of a stimulus until the organism responds. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together
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in either parent; usually applied to linked genes. [EU] Recombinant Proteins: Proteins prepared by recombinant DNA technology. [NIH] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Rectovaginal Fistula: Abnormal communication between the rectum and the vagina. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflex: An involuntary movement or exercise of function in a part, excited in response to a stimulus applied to the periphery and transmitted to the brain or spinal cord. [NIH] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Regurgitation: A backward flowing, as the casting up of undigested food, or the backward flowing of blood into the heart, or between the chambers of the heart when a valve is incompetent. [EU] 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] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Renal pelvis: The area at the center of the kidney. Urine collects here and is funneled into the ureter, the tube that connects the kidney to the bladder. [NIH] Renal Replacement Therapy: Procedures which temporarily or permanently remedy insufficient cleansing of body fluids by the kidneys. [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] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Respiratory distress syndrome: A lung disease that occurs primarily in premature infants; the newborn must struggle for each breath and blueing of its skin reflects the baby's inability
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to get enough oxygen. [NIH] Retreatment: The therapy of the same disease in a patient, with the same agent or procedure repeated after initial treatment, or with an additional or alternate measure or follow-up. It does not include therapy which requires more than one administration of a therapeutic agent or regimen. Retreatment is often used with reference to a different modality when the original one was inadequate, harmful, or unsuccessful. [NIH] Retropubic: A potential space between the urinary bladder and the symphisis and body of the pubis. [NIH] Retropubic prostatectomy: Surgery to remove the prostate through an incision made in the abdominal wall. [NIH] Retrospective: Looking back at events that have already taken place. [NIH] Retrospective study: A study that looks backward in time, usually using medical records and interviews with patients who already have or had a disease. [NIH] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [NIH] Reversion: A return to the original condition, e. g. the reappearance of the normal or wild type in previously mutated cells, tissues, or organisms. [NIH] Rheumatic Heart Disease: Disease of the heart resulting from rheumatic fever and characterized by inflammatory changes in the myocardium or scarring of the valves. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Rodenticides: Substances used to destroy or inhibit the action of rats, mice, or other rodents. [NIH]
Saline: A solution of salt and water. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Salivary Proteins: Proteins found in saliva and the salivary glands. These proteins show some enzymatic activity, but their composition varies in different individuals. [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] Screening: Checking for disease when there are no symptoms. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to
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as epilepsy or "seizure disorder." [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Sensibility: The ability to receive, feel and appreciate sensations and impressions; the quality of being sensitive; the extend to which a method gives results that are free from false negatives. [NIH] Sepsis: The presence of bacteria in the bloodstream. [NIH] 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] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [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] Serum Albumin: A major plasma protein that serves in maintaining the plasma colloidal osmotic pressure and transporting large organic anions. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]
Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Sinusitis: An inflammatory process of the mucous membranes of the paranasal sinuses that occurs in three stages: acute, subacute, and chronic. Sinusitis results from any condition causing ostial obstruction or from pathophysiologic changes in the mucociliary transport mechanism. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH]
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Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]
Sneezing: Sudden, forceful, involuntary expulsion of air from the nose and mouth caused by irritation to the mucous membranes of the upper respiratory tract. [NIH] Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Social Support: Support systems that provide assistance and encouragement to individuals with physical or emotional disabilities in order that they may better cope. Informal social support is usually provided by friends, relatives, or peers, while formal assistance is provided by churches, groups, etc. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Sodium Channels: Cell membrane glycoproteins selective for sodium ions. Fast sodium current is associated with the action potential in neural membranes. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [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] Spectrophotometry: The art or process of comparing photometrically the relative intensities of the light in different parts of the spectrum. [NIH] Spectroscopic: The recognition of elements through their emission spectra. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Spermatozoa: Mature male germ cells that develop in the seminiferous tubules of the testes. Each consists of a head, a body, and a tail that provides propulsion. The head consists mainly of chromatin. [NIH] Sphenoid: An unpaired cranial bone with a body containing the sphenoid sinus and forming the posterior part of the medial walls of the orbits. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in
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the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spinous: Like a spine or thorn in shape; having spines. [NIH] Spirochete: Lyme disease. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] 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] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] 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] Sterile: Unable to produce children. [NIH] Steroids: Drugs used to relieve swelling and inflammation. [NIH] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]
Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] 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] Stress incontinence: An involuntary loss of urine that occurs at the same time that internal abdominal pressure is increased, such as with laughing, sneezing, coughing, or physical activity. [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] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [EU]
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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] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]
Substrate: A substance upon which an enzyme acts. [EU] 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] Sulfates: Inorganic salts of sulfuric acid. [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] Suspensions: Colloids with liquid continuous phase and solid dispersed phase; the term is used loosely also for solid-in-gas (aerosol) and other colloidal systems; water-insoluble drugs may be given as suspensions. [NIH] Sympathetic Nervous System: The thoracolumbar division of the autonomic nervous system. Sympathetic preganglionic fibers originate in neurons of the intermediolateral column of the spinal cord and project to the paravertebral and prevertebral ganglia, which in turn project to target organs. The sympathetic nervous system mediates the body's response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system. [NIH] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Syphilis: A contagious venereal disease caused by the spirochete Treponema pallidum. [NIH]
Systemic: Affecting the entire body. [NIH] 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] Tachycardia: Excessive rapidity in the action of the heart, usually with a heart rate above 100 beats per minute. [NIH] Theophylline: Alkaloid obtained from Thea sinensis (tea) and others. It stimulates the heart and central nervous system, dilates bronchi and blood vessels, and causes diuresis. The drug is used mainly in bronchial asthma and for myocardial stimulation. Among its more prominent cellular effects are inhibition of cyclic nucleotide phosphodiesterases and
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antagonism of adenosine receptors. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] 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] Thoracic Surgery: A surgical specialty concerned with diagnosis and treatment of disorders of the heart, lungs, and esophagus. Two major types of thoracic surgery are classified as pulmonary and cardiovascular. [NIH] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombocytes: Blood cells that help prevent bleeding by causing blood clots to form. Also called platelets. [NIH] 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] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]
Thrombopenia: Reduction in the number of platelets in the blood. [NIH] Thrombophilia: A disorder of hemostasis in which there is a tendency for the occurrence of thrombosis. [NIH] Thrombophlebitis: Inflammation of a vein associated with thrombus formation. [NIH] Thromboplastin: Constituent composed of protein and phospholipid that is widely distributed in many tissues. It serves as a cofactor with factor VIIa to activate factor X in the extrinsic pathway of blood coagulation. [NIH] 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] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Ticks: Blood-sucking arachnids of the order Acarina. [NIH] Ticlopidine: Ticlopidine is an effective inhibitor of platelet aggregation. The drug has been
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found to significantly reduce infarction size in acute myocardial infarcts and is an effective antithrombotic agent in arteriovenous fistulas, aorto-coronary bypass grafts, ischemic heart disease, venous thrombosis, and arteriosclerosis. [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] Tonicity: The normal state of muscular tension. [NIH] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] Torsion: A twisting or rotation of a bodily part or member on its axis. [NIH] 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] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transient Ischemic Attacks: Focal neurologic abnormalities of sudden onset and brief duration that reflect dysfunction in the distribution of the internal carotid-middle cerebral or the vertebrobasilar arterial system. [NIH] 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] 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] Transurethral: Performed through the urethra. [EU] Transurethral resection: Surgery performed with a special instrument inserted through the urethra. Also called TUR. [NIH]
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Transurethral Resection of Prostate: Resection of the prostate using a cystoscope passed through the urethra. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [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] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [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]
Ulceration: 1. The formation or development of an ulcer. 2. An ulcer. [EU] Ultrafiltration: The separation of particles from a suspension by passage through a filter with very fine pores. In ultrafiltration the separation is accomplished by convective transport; in dialysis separation relies instead upon differential diffusion. Ultrafiltration occurs naturally and is a laboratory procedure. Artificial ultrafiltration of the blood is referred to as hemofiltration or hemodiafiltration (if combined with hemodialysis). [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Uremia: The illness associated with the buildup of urea in the blood because the kidneys are not working effectively. Symptoms include nausea, vomiting, loss of appetite, weakness, and mental confusion. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]
Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary Fistula: An abnormal passage in any organ of the urinary tract or between urinary organs and other organs. [NIH] Urinary tract: The organs of the body that produce and discharge urine. These include the kidneys, ureters, bladder, and urethra. [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] Vaccines: Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa, or rickettsiae), antigenic proteins derived from them, or synthetic constructs, administered for the prevention, amelioration, or treatment of infectious and other diseases. [NIH]
Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH]
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Valproic Acid: A fatty acid with anticonvulsant properties used in the treatment of epilepsy. The mechanisms of its therapeutic actions are not well understood. It may act by increasing GABA levels in the brain or by altering the properties of voltage dependent sodium channels. [NIH] Valves: Flap-like structures that control the direction of blood flow through the heart. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasculitis: Inflammation of a blood vessel. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] Vasomotor: 1. Affecting the calibre of a vessel, especially of a blood vessel. 2. Any element or agent that effects the calibre of a blood vessel. [EU] 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] Venereal: Pertaining or related to or transmitted by sexual contact. [EU] Venom: That produced by the poison glands of the mouth and injected by the fangs of poisonous snakes. [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] 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] Vertebral: Of or pertaining to a vertebra. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Villi: The tiny, fingerlike projections on the surface of the small intestine. Villi help absorb nutrients. [NIH] Villous: Of a surface, covered with villi. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH]
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Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] 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. [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] Zoster: A virus infection of the Gasserian ganglion and its nerve branches, characterized by discrete areas of vesiculation of the epithelium of the forehead, the nose, the eyelids, and the cornea together with subepithelial infiltration. [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]
211
INDEX A Abdominal, 151, 190, 192, 200, 203 Acceptor, 151, 183, 190 Acetaminophen, 139, 151 Acetylcholine, 151, 188, 189 Acetylgalactosamine, 151 Acetylglucosamine, 151 Acrosin, 105, 151 Acute renal, 16, 96, 151, 177 Acylation, 112, 151 Adaptation, 33, 151 Adenine, 44, 151, 197 Adenosine, 41, 151, 192, 205 Adhesives, 101, 151 Adjustment, 151 Adrenal Cortex, 151, 165, 195 Adrenergic, 151, 156, 168, 195 Adverse Effect, 5, 11, 18, 101, 152, 192, 201 Aerosol, 152, 204 Affinity, 8, 10, 13, 22, 152, 156, 183, 202 Affinity Chromatography, 8, 152 Agar, 152, 193 Alanine, 14, 152 Albumin, 12, 27, 152, 193 Algorithms, 152, 158 Alkaline, 152, 159 Alternative medicine, 123, 152 Aluminum, 40, 152 Amine, 152, 177 Amino Acid Sequence, 153, 154, 175 Amino Acids, 19, 99, 153, 162, 171, 175, 191, 194, 196, 201, 206 Ampulla, 153, 170 Anaesthesia, 41, 65, 66, 153, 179 Analgesic, 151, 153 Anaphylatoxins, 153, 164 Anatomical, 153, 156, 162, 179, 186 Anemia, 5, 82, 153, 187 Anesthesia, 5, 44, 60, 63, 153, 156, 169 Anesthetics, 103, 153 Aneurysm, 74, 153 Angina, 11, 153, 189, 195 Angiography, 102, 153 Angioplasty, 32, 95, 102, 108, 115, 153, 156 Animal model, 11, 15, 98, 153 Anionic, 22, 153 Anions, 152, 153, 181, 201 Annealing, 154, 194
Annexins, 22, 154 Antagonism, 29, 89, 154, 205 Antibacterial, 61, 81, 154, 202 Antibiotic, 154, 162, 171, 191, 202 Antibodies, 17, 22, 23, 31, 32, 36, 53, 57, 58, 71, 98, 99, 139, 154, 155, 156, 176, 179, 187, 193 Antibodies, Anticardiolipin, 154, 155 Antibodies, Antiphospholipid, 154, 155 Antibody, 22, 31, 49, 111, 139, 152, 154, 155, 163, 166, 170, 171, 176, 178, 179, 180, 182, 187, 198, 202, 209 Anticonvulsant, 10, 154, 192, 208 Antidote, 11, 122, 154, 159 Antifungal, 62, 81, 154 Antifungal Agents, 62, 154 Antigen, 36, 55, 152, 154, 155, 160, 164, 171, 178, 179, 180, 186, 198 Antigen-Antibody Complex, 155, 164 Anti-inflammatory, 81, 110, 151, 155, 156 Anti-Inflammatory Agents, 110, 155, 156 Antioxidant, 18, 155, 190 Antiphospholipid Syndrome, 22, 53, 57, 63, 139, 154, 155 Antipyretic, 151, 155 Antithrombins, 32, 155 Antithrombotic, 9, 15, 19, 50, 62, 98, 104, 105, 110, 140, 155, 177, 206 Antituberculosis, 81, 155 Antiviral, 81, 155, 181 Aorta, 59, 155, 165, 176, 208 Apheresis, 93, 99, 155 Apolipoproteins, 155, 183 Apoptosis, 18, 155, 166 Aqueous, 92, 112, 155, 157, 166, 182 Arginine, 41, 153, 155, 189, 193, 207 Arteries, 15, 115, 155, 156, 158, 159, 161, 165, 176, 182, 183, 188 Arterioles, 155, 156, 158 Arteriosclerosis, 155, 206 Arteriovenous, 5, 96, 156, 206 Arteriovenous Fistula, 5, 156, 206 Arthroplasty, 63, 156 Aspergillosis, 30, 156 Aspirin, 6, 17, 24, 29, 35, 41, 50, 61, 63, 85, 122, 139, 156 Assay, 15, 26, 36, 39, 56, 67, 100, 109, 156, 179, 198
212
Anticoagulants
Astrocytes, 156, 186, 187 Atenolol, 5, 156 Atherectomy, 102, 156, 169 Atrial, 4, 6, 13, 27, 30, 43, 50, 52, 56, 61, 64, 65, 66, 67, 101, 122, 156, 209 Atrial Fibrillation, 4, 6, 13, 27, 30, 50, 52, 61, 64, 65, 66, 67, 101, 122, 156, 209 Atrium, 101, 156, 186, 208 Atrophy, 156, 172 Attenuated, 156, 167, 207 Auricular, 101, 156 Autoantibodies, 17, 37, 154, 156 Autoantigens, 156 Autoimmune disease, 111, 140, 154, 156, 157 Autoimmunity, 35, 39, 94, 140, 157 Autologous, 7, 94, 157 B Bacteria, 20, 154, 157, 162, 169, 170, 176, 186, 201, 202, 203, 206, 207 Bacterial Physiology, 151, 157 Bactericidal, 110, 157 Base, 16, 40, 151, 157, 174, 182 Basement Membrane, 157, 172, 182 Benzodiazepines, 18, 157 Bilateral, 5, 31, 119, 157 Bile, 102, 157, 175, 182, 183, 184 Bile Acids, 157 Bile Acids and Salts, 157 Bile duct, 102, 157 Bile Pigments, 157, 182, 184 Bilirubin, 152, 157, 175, 178 Binding Sites, 13, 157 Bioavailability, 5, 114, 157 Biochemical, 11, 23, 42, 47, 107, 157, 158, 173, 192 Biochemical reactions, 107, 157 Biocompatible Materials, 110, 157 Biological response modifier, 157, 158, 180 Biological therapy, 158, 176 Biological Transport, 158, 167 Biopolymers, 104, 158 Biopsy, 102, 103, 158, 191 Biosynthesis, 158, 196, 201 Biotechnology, 25, 28, 81, 123, 133, 158 Bivalent, 31, 158 Bladder, 158, 179, 196, 199, 200, 207 Blood Coagulation Factors, 158, 163 Blood Coagulation Tests, 158, 181 Blood Platelets, 105, 158, 205 Blood pressure, 150, 158, 160, 178, 187, 192, 202
Blood-Brain Barrier, 20, 158 Body Fluids, 93, 158, 159, 168, 199, 202 Bone Density, 9, 158 Bone Marrow, 20, 57, 102, 158, 159, 171, 174, 179, 183, 187 Bone Marrow Transplantation, 20, 57, 159 Brachial, 159, 198 Brachial Artery, 159, 198 Brachytherapy, 159, 181, 182, 198, 209 Bradycardia, 159, 173 Bradykinin, 159, 189, 193 Brain Hypoxia, 159 Brain Infarction, 19, 159 Brain Ischemia, 46, 159 Brain Stem, 159, 161 Brain Stem Infarctions, 159 Bronchi, 159, 204 Bronchial, 159, 177, 204 Buccal, 159, 177, 183 Bypass, 35, 41, 50, 63, 159, 205, 206 C Calcium, 22, 41, 96, 154, 159, 163, 184, 191, 197, 201 Calcium Chloride, 96, 159, 191 Capsules, 159, 173 Carbohydrate, 160, 175, 194 Carbon Dioxide, 160, 166, 174, 193, 199, 208 Carboxypeptidases, 39, 160 Carcinogenic, 160, 180, 195 Carcinoma, 118, 160 Cardiac, 12, 13, 33, 37, 43, 54, 101, 122, 156, 160, 170, 176, 188 Cardiolipins, 155, 160 Cardiorespiratory, 12, 160 Cardioselective, 156, 160, 195 Cardiovascular, 7, 17, 28, 35, 38, 47, 52, 63, 67, 74, 81, 102, 117, 118, 139, 160, 205 Cardiovascular disease, 17, 160 Cardioversion, 65, 160 Carrier Proteins, 160, 193, 198 Case report, 5, 17, 31, 160 Cataract, 71, 102, 160 Catheter, 115, 156, 160, 169 Catheterization, 153, 160 Cathode, 160, 169 Cations, 104, 160, 181 Cauda Equina, 43, 161 Cause of Death, 10, 20, 161 Cavernous Sinus, 66, 161 Cell Death, 155, 161, 188
213
Cell Division, 157, 161, 176, 185, 186, 193, 195 Cell membrane, 158, 160, 161, 182, 185, 192, 202 Cell Size, 161, 173 Cell Survival, 161, 176 Central Nervous System, 151, 152, 161, 174, 186, 204 Cerebellar, 48, 161 Cerebellum, 159, 161 Cerebral, 19, 30, 33, 61, 69, 113, 158, 159, 161, 165, 186, 206 Cerebral Arteries, 161, 186 Cerebral hemispheres, 159, 161 Cerebral Infarction, 159, 161 Cerebrovascular, 20, 69, 109, 119, 160, 161 Cerebrum, 161 Chelating Agents, 92, 161 Chemotactic Factors, 162, 164 Chemotherapeutic agent, 162, 167 Chemotherapy, 161, 162 Chin, 162, 185 Chlorophyll, 161, 162 Cholesterol, 83, 157, 162, 165, 183, 185 Cholesterol Esters, 162, 183 Chondroitin sulfate, 104, 162 Chromatin, 155, 162, 184, 202 Chronic, 27, 33, 45, 138, 162, 163, 180, 194, 201, 203, 204 Chylomicrons, 162, 183 Chymotrypsin, 104, 162 CIS, 14, 162 Clarithromycin, 49, 162 Clear cell carcinoma, 162, 167 Cleave, 105, 162 Clinical Medicine, 50, 162, 195 Clinical trial, 6, 17, 23, 34, 133, 162, 165, 191, 198 Cloning, 158, 162 Clot Retraction, 163, 193 Coagulants, 103, 117, 163 Coagulation, 4, 5, 7, 9, 11, 17, 19, 20, 22, 25, 27, 38, 39, 40, 42, 48, 49, 51, 53, 58, 67, 68, 95, 97, 98, 99, 100, 104, 106, 107, 108, 109, 110, 111, 113, 155, 158, 159, 163, 172, 177, 191, 193, 205, 209 Cofactor, 9, 13, 26, 100, 110, 163, 196, 205 Cognition, 17, 163 Collagen, 21, 103, 107, 108, 151, 157, 163, 164, 172, 184, 193, 195 Collagen disease, 163, 172 Colloidal, 152, 163, 201, 204
Colon, 163, 168 Combination Therapy, 163, 171 Comorbidity, 18, 65, 119, 163 Complement, 15, 153, 163, 164, 193 Complementary and alternative medicine, 79, 80, 88, 164 Complementary medicine, 80, 164 Computational Biology, 133, 164 Concomitant, 79, 109, 164 Congestion, 164, 171 Congestive heart failure, 114, 164 Conjugated, 157, 164, 166 Connective Tissue, 155, 159, 163, 164, 174, 204 Connective Tissue Diseases, 155, 164 Consciousness, 153, 164, 166, 167 Constriction, 164, 182 Consultation, 6, 164 Contraindications, ii, 5, 164 Contrast medium, 153, 165 Controlled study, 55, 165 Convulsions, 154, 165, 168, 195 Coordination, 16, 161, 165 Cornea, 165, 175, 209 Corneal Ulcer, 105, 165 Corneum, 165, 171 Coronary, 4, 8, 9, 11, 25, 31, 52, 59, 60, 63, 70, 95, 101, 108, 109, 115, 160, 165, 188, 189, 206 Coronary Artery Bypass, 11, 165 Coronary heart disease, 160, 165 Coronary Thrombosis, 59, 165, 188 Corpus, 106, 165, 195 Corpus Luteum, 106, 165, 195 Cortex, 161, 165, 186 Cortical, 165, 200 Corticosteroids, 139, 165 Cortisol, 152, 165 Coumarin, 4, 10, 32, 34, 36, 37, 38, 52, 62, 89, 165 Critical Care, 29, 40, 41, 43, 69, 165 Curative, 165, 205 Cutaneous, 29, 36, 62, 138, 165, 183, 190 Cyclic, 83, 165, 176, 189, 196, 204 Cysteine, 160, 166 Cysteinyl, 105, 166 Cytochrome, 17, 166 Cytokines, 20, 166, 186 Cytoplasm, 155, 161, 166, 184, 187 D Data Collection, 16, 166 Decarboxylation, 166, 177
214
Anticoagulants
Degenerative, 166, 177 Deletion, 23, 155, 166 Dementia, 63, 83, 84, 139, 166 Denaturation, 166, 194 Dental Care, 5, 166 Dentists, 4, 5, 6, 119, 166 Dermatitis, 166, 194 Dermatology, 36, 102, 166 DES, 74, 153, 166 Deuterium, 167, 178 Developed Countries, 99, 167 Diagnostic Errors, 167, 184 Diagnostic procedure, 91, 123, 167 Dialysate, 96, 119, 167 Dialyzer, 119, 167, 176 Diarrhea, 167, 192 Diastolic, 167, 178 Diffusion, 96, 158, 167, 180, 199, 207 Digestion, 103, 105, 157, 167, 183, 203 Dilation, 156, 159, 167 Dilator, 167, 189 Dilution, 92, 167 Dipyridamole, 41, 85, 126, 167 Direct, iii, 17, 59, 105, 109, 125, 160, 162, 167, 168, 178, 183, 198, 199 Discoid, 138, 167 Discrete, 10, 167, 209 Disposition, 34, 167 Dissociation, 152, 167, 181 Distal, 102, 165, 167, 197 Diuresis, 168, 204 Diuretic, 159, 168 Diverticula, 168 Diverticulitis, 168 Diverticulosis, 32, 168 Dopamine, 168, 187, 188 Dose-dependent, 110, 168 Drive, ii, vi, 15, 73, 100, 118, 119, 168 Drug Combinations, 80, 168 Drug Interactions, 10, 126, 127, 168 Drug Tolerance, 168, 206 Duct, 153, 160, 168, 171, 200 Duodenum, 157, 162, 168, 170, 190, 203 Dura mater, 161, 168 E Echocardiography, 56, 168 Eclampsia, 168, 195 Edema, 83, 108, 168, 194, 195, 208 Effector, 151, 163, 168 Efficacy, 18, 20, 26, 41, 65, 67, 89, 168 Elastic, 7, 168 Elasticity, 7, 155, 169
Elastin, 103, 163, 164, 169, 172 Elective, 25, 169 Electrocoagulation, 163, 169 Electrolysis, 154, 160, 169 Electrolyte, 41, 169, 176, 194, 202 Electrons, 155, 157, 160, 169, 181, 184, 190, 198 Elementary Particles, 169, 184, 189, 197 Ellagic Acid, 169, 191 Emboli, 70, 169, 209 Embolism, 6, 113, 169, 197, 209 Embolization, 169, 209 Embolus, 105, 119, 169, 179 Embryo, 106, 169, 179 Emergency Treatment, 119, 169 Emollient, 169, 175 Emphysema, 105, 169 Endarterectomy, 153, 156, 169 Endocarditis, 5, 169 Endocardium, 169, 170 Endocrinology, 170, 176 Endogenous, 12, 19, 155, 156, 158, 163, 168, 170, 175 Endonucleases, 12, 170 Endoscope, 170 Endoscopic, 102, 170 Endoscopy, 43, 54, 65, 170 Endothelial cell, 15, 20, 64, 100, 101, 105, 110, 158, 170, 205 Endothelium, 15, 26, 170, 189, 193 Endothelium, Lymphatic, 170 Endothelium, Vascular, 170 Endothelium-derived, 170, 189 Endotoxin, 20, 50, 170 Enoxaparin, 65, 170 Enteropeptidase, 170, 207 Environmental Health, 132, 134, 170 Enzymatic, 103, 159, 164, 170, 173, 177, 185, 194, 200 Enzyme Inhibitors, 105, 170, 193 Enzyme-Linked Immunosorbent Assay, 36, 170 Epidemic, 114, 171 Epidemiological, 23, 171 Epidermis, 102, 165, 171, 178 Epigastric, 171, 190 Epithelial, 158, 165, 171, 177, 182, 196 Epithelial Cells, 171, 177, 182, 196 Epithelium, 157, 170, 171, 209 Epitope, 23, 98, 171 Erythema, 103, 171 Erythrocytes, 153, 159, 171, 199
215
Erythromycin, 162, 171 Erythropoietin, 93, 171 Esophagus, 171, 203, 205 Estrogen, 13, 171 Estrogen Replacement Therapy, 13, 171 Excitation, 171, 173, 188 Exhaustion, 154, 171 Exocrine, 171, 190 Exogenous, 100, 163, 170, 171, 175 External-beam radiation, 172, 182, 198, 209 Extracellular, 22, 99, 103, 106, 156, 164, 172, 184, 202 Extracellular Matrix, 103, 106, 164, 172, 184 Extracellular Matrix Proteins, 172, 184 Extracellular Space, 106, 172 Extracorporeal, 12, 95, 96, 119, 172, 176 Extracorporeal Circulation, 12, 95, 172 Extraction, 104, 172 Extravasation, 172, 176 F Factor X, 7, 25, 42, 97, 98, 112, 169, 172 Factor Xa, 7, 25, 98, 112, 172 Family Planning, 133, 172 Fat, 157, 158, 165, 169, 172, 183, 202 Fatty acids, 152, 172, 175, 184, 196 Femoral, 42, 45, 102, 172 Femoral Nerve, 172 Femoral Neuropathy, 45, 172 Femur, 172 Fetal Distress, 22, 173 Fetal Viability, 22, 173 Fetus, 171, 173, 184, 192, 195, 207 Fibrillation, 101, 173 Fibrin, 8, 19, 39, 56, 95, 102, 105, 106, 109, 113, 158, 163, 173, 191, 193, 205, 206 Fibrinogen, 95, 106, 113, 173, 191, 193, 197, 205 Fibrinolysis, 19, 38, 39, 40, 42, 45, 48, 67, 68, 94, 107, 113, 173 Fibrinolytic, 19, 42, 94, 173, 205 Fibrinolytic Agents, 94, 173, 205 Fibronectin, 99, 103, 106, 173 Filler, 101, 173 Filtration, 8, 173 Flatus, 173, 174 Flexion, 172, 173 Flow Cytometry, 80, 173 Fluorescence, 11, 14, 19, 80, 173 Fluorescent Dyes, 173 Fluorouracil, 167, 173
Flutter, 30, 174 Fold, 13, 174, 190 Foramen, 47, 162, 174 Forearm, 35, 158, 174, 198 Fossa, 5, 161, 174 Free Radicals, 155, 167, 174 Fungicides, Industrial, 154, 174 G Ganglia, 151, 159, 174, 188, 204 Ganglion, 174, 209 Gangrene, 94, 174 Gas, 12, 36, 40, 41, 160, 167, 173, 174, 178, 189, 204, 208 Gas exchange, 12, 174, 208 Gastric, 174, 177, 178 Gastrin, 174, 178 Gastrointestinal, 5, 43, 47, 65, 102, 159, 174, 203, 204 Gastrointestinal tract, 174, 203 Gene, 14, 15, 158, 174, 181 Gene Expression, 174 Gene Therapy, 15, 174 Genetic Code, 174, 189 Genetic testing, 175, 194 Genetics, 14, 42, 138, 175 Genital, 162, 175, 176 Gestation, 9, 175, 193 Ginkgo biloba, 139, 175 Gland, 7, 23, 119, 151, 175, 177, 190, 196, 200, 203, 205 Glomerular, 105, 175, 199 Glomerulus, 175, 188 Glucose, 175, 176, 180 Glucuronic Acid, 104, 175, 177, 178 Glucuronides, 175 Glycerol, 7, 160, 175, 192 Glycerophospholipids, 175, 192 Glycine, 157, 175, 188, 201 Glycoprotein, 28, 31, 36, 40, 54, 99, 108, 111, 171, 172, 173, 175, 182, 205 Glycosaminoglycan, 162, 175 Glycosidic, 8, 175 Governing Board, 175, 195 Graft, 11, 176 Grafting, 35, 63, 102, 165, 176, 179 Gram-negative, 20, 108, 176 Granule, 176, 193 Growth factors, 110, 176, 186 Guanylate Cyclase, 176, 189 Gynecology, 34, 61, 69, 102, 176 H Haptens, 152, 176, 198
216
Anticoagulants
Health Services, 16, 176 Heart attack, 8, 11, 95, 101, 108, 160, 176 Heart failure, 176 Heart Valves, 4, 7, 60, 111, 176 Heartbeat, 110, 176 Heart-Lung Machine, 95, 176 Hematology, 41, 53, 64, 68, 80, 117, 176 Hematoma, 5, 119, 176 Hemodiafiltration, 12, 176, 207 Hemodialysis, 5, 46, 62, 95, 96, 119, 167, 176, 207 Hemofiltration, 119, 176, 207 Hemoglobin, 153, 161, 171, 176, 177, 190 Hemoglobin A, 161, 177 Hemoglobinopathies, 174, 177 Hemolytic, 177, 203 Hemorrhage, 4, 5, 6, 17, 20, 35, 43, 61, 97, 169, 177, 203 Hemostasis, 13, 14, 21, 27, 30, 37, 52, 56, 100, 102, 107, 108, 177, 181, 205 Hepatic, 102, 152, 177 Hepatitis, 26, 38, 177 Hepatocytes, 177 Heredity, 174, 175, 177 Heritability, 14, 177 Heterogeneity, 47, 152, 177 Hirudin, 48, 177 Histamine, 21, 153, 177 Histidine, 177 Homeostasis, 22, 96, 177 Homologous, 7, 23, 110, 154, 158, 174, 177 Hormonal, 110, 156, 171, 178 Hormone, 74, 165, 166, 171, 174, 178, 180, 195, 200, 201 Horny layer, 171, 178 Horseradish Peroxidase, 170, 178 Hybrid, 10, 178 Hybridoma, 47, 178 Hydrochloric Acid, 8, 178 Hydrogen, 7, 97, 98, 151, 152, 157, 160, 166, 167, 172, 178, 183, 187, 189, 190, 192, 197 Hydrogen Bonding, 7, 178 Hydrogenation, 157, 178 Hydrolysis, 170, 178, 194, 196, 207 Hydrophobic, 108, 175, 178, 183 Hydroxylysine, 163, 178 Hydroxyproline, 163, 178 Hyperbilirubinemia, 178, 182 Hypersensitivity, 178, 179, 200 Hypertension, 18, 33, 83, 84, 160, 178, 195
I Iduronic Acid, 104, 178 Immune response, 23, 106, 154, 156, 157, 176, 178, 179, 204, 208 Immune system, 20, 157, 158, 178, 179, 184, 209 Immunity, 152, 179 Immunization, 179, 195 Immunoassay, 48, 154, 170, 179 Immunogenic, 179, 198 Immunoglobulins, 118, 179, 193 Immunologic, 27, 53, 162, 179, 198 Immunologic Tests, 53, 179 Immunology, 36, 39, 51, 152, 173, 178, 179 Immunosuppressive, 79, 179 Impairment, 22, 179, 185, 208 Implant radiation, 179, 181, 182, 198, 209 Implantation, 7, 110, 179 Impotence, 119, 179 In situ, 15, 179 In vitro, 7, 8, 9, 15, 19, 22, 40, 70, 74, 89, 94, 107, 111, 174, 179, 194 In vivo, 7, 8, 9, 15, 19, 21, 22, 26, 94, 105, 107, 174, 177, 179 Incision, 179, 181, 196, 200 Incontinence, 119, 179 Incubation, 40, 179 Induction, 108, 179 Infarction, 161, 179, 199, 206 Infection, 46, 103, 158, 162, 165, 180, 183, 188, 191, 200, 204, 209 Inferior vena cava, 59, 180 Infertility, 180, 182 Infiltration, 180, 209 Inflammation, 20, 97, 139, 152, 155, 156, 166, 168, 177, 180, 188, 194, 203, 204, 205, 208 Infusion, 22, 96, 180 Ingestion, 180, 194 Inhalation, 152, 180, 194 Initiation, 23, 50, 74, 108, 180 Initiator, 108, 180 Inotropic, 156, 168, 180 Insight, 8, 9, 20, 180 Insulin, 80, 93, 180 Insulin-dependent diabetes mellitus, 180 Intensive Care, 20, 43, 180 Intensive Care Units, 20, 180 Interferon, 93, 180, 181 Interferon-alpha, 180, 181 Interleukin-1, 94, 181 Interleukin-10, 94, 181
217
Interleukin-2, 181 Intermittent, 29, 181, 192 Intermittent Claudication, 29, 181 Internal Medicine, 9, 23, 24, 38, 45, 52, 56, 62, 63, 170, 176, 181, 188 Internal radiation, 181, 182, 198, 209 International Normalized Ratio, 4, 27, 38, 181 Interstitial, 159, 172, 181, 182, 185, 188, 199, 209 Intestinal, 104, 170, 181, 184 Intestines, 151, 174, 181, 184 Intracellular, 103, 180, 181, 185, 189, 194, 196, 201 Intravascular, 20, 64, 108, 181 Intravenous, 109, 180, 181 Intrinsic, 94, 95, 97, 152, 157, 172, 181, 190 Invasive, 30, 102, 179, 181, 184, 190 Invertebrates, 9, 181 Involuntary, 173, 181, 188, 199, 202, 203 Ionization, 36, 181 Ions, 157, 161, 167, 169, 178, 181, 197, 202 Irradiation, 118, 182, 209 Ischemia, 19, 34, 101, 156, 159, 172, 182, 199 Ischemic stroke, 19, 24, 30, 31, 57, 69, 182 Isotonic, 103, 182, 186 J Jaundice, 45, 178, 182 K Kallikreins, 105, 182 Kb, 132, 182 Kinetic, 11, 14, 182 L Labile, 163, 182 Laminin, 103, 157, 172, 182 Latent, 182, 195 Lens, 160, 182 Lesion, 103, 165, 182 Lethal, 20, 157, 182 Leukapheresis, 155, 182 Leukemia, 174, 182 Life cycle, 23, 182 Life Expectancy, 119, 183 Ligament, 183, 196 Ligands, 10, 21, 183 Linkages, 176, 183, 203 Lipid, 19, 47, 155, 156, 175, 180, 183, 190 Lipid Peroxidation, 183, 190 Lipophilic, 17, 183 Lipopolysaccharide, 20, 26, 176, 183 Lipoprotein, 19, 110, 176, 183, 193
Liver, 12, 21, 37, 52, 57, 102, 151, 152, 157, 171, 175, 177, 183, 187 Loc, 100, 183 Localized, 159, 176, 180, 182, 183, 193, 205 Locoregional, 44, 183 Loop, 102, 108, 183 Low-density lipoprotein, 183 Lucida, 182, 183 Lumbar, 161, 172, 183 Lymph, 170, 183 Lymphatic, 170, 180, 183, 203 Lymphatic system, 183, 203 Lymphocytes, 154, 179, 181, 184, 203, 209 Lymphoid, 154, 165, 184 Lysine, 178, 184, 207 Lytic, 94, 95, 184, 201 M Macrophage, 181, 184 Magnetic Resonance Imaging, 184 Magnetic Resonance Spectroscopy, 9, 184 Malignancy, 24, 68, 184 Malignant, 184, 187, 188, 196, 198 Malignant tumor, 184, 187 Malnutrition, 152, 156, 184 Malondialdehyde, 48, 184 Mammary, 165, 184 Mandible, 5, 162, 184 Manifest, 106, 184 Matrix metalloproteinase, 39, 184 Meat, 92, 184 Meconium, 173, 184 Medial, 156, 172, 184, 202 Medical Errors, 15, 184 Medical Records, 185, 200 Medication Errors, 16, 185 MEDLINE, 133, 185 Meiosis, 158, 185 Melanocytes, 185 Melanoma, 68, 185 Membrane, 14, 16, 22, 93, 96, 101, 110, 154, 156, 161, 164, 167, 176, 182, 185, 187, 189, 190, 192, 193, 199, 201, 206 Membrane Fusion, 154, 185 Membrane Lipids, 185, 192 Memory, 166, 185 Menstrual Cycle, 185, 195 Mental, iv, 6, 16, 132, 134, 162, 163, 166, 167, 185, 189, 195, 197, 207 Mental Disorders, 185, 195 Mental Health, iv, 6, 132, 134, 185, 189, 195 Mental Processes, 167, 185, 197
218
Anticoagulants
Mercury, 173, 185 Meta-Analysis, 53, 61, 186 Metabolite, 10, 186, 195 Metaphase, 158, 186 Metastasis, 184, 186 Microbe, 106, 186, 206 Microbiology, 30, 39, 151, 186 Microglia, 156, 186, 187 Microorganism, 163, 186, 191, 209 Microscopy, 80, 157, 178, 186 Middle Cerebral Artery, 19, 186 Milliliter, 158, 186 Miscarriage, 111, 186 Mitochondrial Swelling, 186, 188 Mitosis, 155, 186 Mitral Valve, 101, 186 Modeling, 10, 11, 34, 186 Modification, 17, 25, 186, 197 Modulator, 109, 187 Molecular mass, 48, 187 Monitor, 7, 16, 66, 67, 122, 187, 189, 191 Monoamine, 79, 187 Monoclonal, 56, 64, 118, 182, 187, 198, 209 Monoclonal antibodies, 64, 118, 187 Monocytes, 20, 94, 181, 187 Mononuclear, 187 Morphological, 169, 185, 187 Morphology, 93, 160, 176, 187 Mucins, 187, 200 Mucociliary, 187, 201 Mucosa, 104, 183, 187 Multiple Myeloma, 25, 187 Multiple Organ Failure, 12, 187 Muscle relaxant, 187, 192 Muscle Spindles, 187, 192 Mutagenesis, 10, 21, 188 Mutagens, 188 Myeloma, 178, 188 Myeloproliferative Disorders, 68, 188 Myocardial infarction, 42, 74, 94, 106, 108, 113, 165, 188, 195, 209 Myocardium, 188, 200 N NCI, 1, 131, 162, 188 Necrosis, 94, 155, 159, 161, 165, 179, 188, 199 Neonatal, 42, 188 Neoplasm, 188, 207 Nephritis, 105, 188 Nephrology, 5, 46, 119, 188 Nephrotoxic, 16, 188 Nervous System, 81, 161, 188, 204
Neurologic, 20, 188, 206 Neurology, 23, 29, 33, 47, 188 Neuropathy, 42, 188 Neurosurgery, 19, 31, 33, 102, 188 Neurotransmitter, 151, 159, 168, 175, 177, 188, 201, 204 Neutralization, 11, 26, 189 Neutrons, 182, 189, 198 Neutrophil, 105, 189 Nitric Oxide, 21, 189 Nitrogen, 152, 172, 187, 189, 207 Nitroglycerin, 5, 189 Nuclear, 9, 33, 39, 56, 169, 174, 188, 189 Nuclei, 169, 174, 184, 186, 189, 197 Nucleic acid, 11, 107, 174, 188, 189, 197 Nucleus, 155, 162, 166, 167, 169, 184, 185, 187, 189, 195, 197, 203 Nursing Care, 189, 191 O Obstetrics, 34, 38, 61, 69, 102, 189 Occupational Medicine, 16, 189 Opacity, 160, 189 Ophthalmic, 102, 189 Oral Surgical Procedures, 55, 189 Organelles, 166, 185, 187, 189 Osmotic, 152, 186, 190, 201 Osteoporosis, 84, 171, 190 Ovarian Follicle, 165, 190 Ovary, 165, 190 Ovum, 165, 175, 182, 190, 195 Oxidation, 17, 151, 155, 166, 183, 190 Oxidative Stress, 18, 190 Oximetry, 64, 190 Oxygenation, 21, 190 Oxygenator, 12, 176, 190 P Palliative, 190, 205 Pancreas, 102, 151, 162, 180, 190, 207 Pancreatic, 162, 190 Pancreatic Juice, 162, 190 Paralysis, 172, 190 Paranasal Sinuses, 190, 201 Paresthesia, 93, 190 Partial Thromboplastin Time, 38, 50, 51, 68, 109, 190 Parturition, 189, 191 Pathogen, 179, 191 Pathologic, 15, 155, 158, 165, 178, 191 Pathologic Processes, 155, 191 Pathophysiology, 19, 23, 66, 191 Patient Care Management, 5, 191 Patient Education, 138, 144, 146, 150, 191
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Patient Selection, 118, 191 Pelvic, 191, 196 Pelvis, 180, 183, 191, 207 Penicillin, 25, 154, 191 Peptide, 25, 26, 59, 105, 162, 170, 191, 194, 196 Peptide Chain Elongation, 162, 191 Percutaneous, 11, 25, 32, 63, 95, 102, 111, 115, 191 Perforation, 174, 191 Perfusion, 12, 114, 191 Pericardium, 191, 204 Perineal, 191, 198 Perioperative, 58, 62, 119, 191 Peripheral Vascular Disease, 11, 191 Peritoneal, 167, 192 Peritoneal Dialysis, 167, 192 PH, 29, 43, 63, 158, 192 Pharmacodynamics, 51, 192 Pharmacokinetic, 16, 34, 192 Pharmacologic, 34, 61, 153, 192, 206 Phenprocoumon, 10, 37, 61, 192 Phenytoin, 10, 16, 192 Phospholipids, 111, 154, 155, 160, 172, 183, 185, 192 Phosphorus, 159, 192 Phosphorylation, 21, 192 Photocoagulation, 163, 192 Physiologic, 12, 34, 158, 182, 185, 192, 196, 198 Physiology, 13, 170, 176, 188, 192 Pigment, 157, 185, 192 Placenta, 192, 195, 197 Plants, 160, 161, 175, 187, 193, 206 Plaque, 108, 153, 156, 193 Plasma cells, 154, 187, 188, 193 Plasma Kallikrein, 182, 193 Plasma protein, 19, 37, 57, 92, 100, 107, 152, 170, 193, 196, 201 Plasmapheresis, 93, 118, 155, 193 Plasmin, 8, 94, 105, 173, 193, 206 Plasminogen Activators, 193 Platelet Activation, 41, 63, 68, 80, 193, 201 Platelet Aggregation, 17, 21, 29, 34, 40, 48, 153, 189, 193, 205 Platelet Aggregation Inhibitors, 21, 193 Platelet Factor 3, 95, 193 Plateletpheresis, 155, 193 Platelets, 31, 37, 44, 51, 93, 95, 99, 100, 108, 109, 113, 189, 193, 194, 205 Pneumonia, 164, 194 Poisoning, 74, 159, 161, 185, 194
Polymerase, 26, 194 Polymerase Chain Reaction, 26, 194 Polymers, 7, 9, 158, 194, 196 Polymorphic, 14, 194 Polymorphism, 14, 194 Polypeptide, 153, 160, 163, 173, 193, 194, 209 Polysaccharide, 104, 154, 175, 194 Posterior, 161, 190, 194, 202 Postmenopausal, 171, 190, 194 Postnatal, 22, 194, 203 Postoperative, 4, 65, 187, 194 Postphlebitic Syndrome, 67, 194 Potassium, 113, 194 Potentiates, 181, 194 Practice Guidelines, 134, 140, 194 Preclinical, 12, 195 Precursor, 8, 99, 168, 170, 195, 196, 207 Predisposition, 100, 139, 195 Preeclampsia, 22, 195 Prenatal, 169, 195 Prevalence, 13, 17, 18, 37, 63, 195 Primary Prevention, 24, 195 Probe, 23, 195 Prodrug, 112, 195 Progesterone, 81, 195 Progression, 112, 153, 195 Progressive, 114, 165, 166, 168, 171, 187, 188, 193, 195, 199, 207 Proline, 163, 178, 195 Promoter, 14, 15, 195 Prophase, 158, 195 Prophylaxis, 5, 30, 95, 118, 195, 209 Propranolol, 156, 195 Prospective Studies, 25, 195 Prostaglandin, 193, 196 Prostate, 84, 118, 182, 196, 198, 200, 207 Prostatectomy, 118, 119, 196, 198 Prostate-Specific Antigen, 182, 196 Prosthesis, 5, 196 Protease, 7, 20, 98, 103, 104, 107, 112, 163, 196, 206 Protease Inhibitors, 104, 107, 112, 196 Protein C, 21, 100, 106, 108, 152, 153, 155, 183, 196 Protein S, 15, 100, 158, 162, 171, 175, 196 Proteinuria, 187, 195, 196 Proteolytic, 13, 103, 104, 105, 112, 164, 170, 173, 182, 193, 196, 206 Prothrombin, 13, 27, 28, 35, 36, 37, 49, 53, 55, 64, 66, 67, 69, 95, 98, 109, 112, 172, 191, 193, 196, 197, 205
220
Anticoagulants
Prothrombin Time, 35, 49, 64, 67, 69, 197 Protons, 178, 184, 197, 198 Proximal, 167, 197 Psychic, 185, 197, 200 Psychology, 16, 167, 197 Pterygoid, 5, 197 Public Policy, 133, 197 Publishing, 25, 197 Puerperium, 189, 197 Pulmonary Artery, 158, 197, 208 Pulmonary Circulation, 101, 197 Pulmonary Embolism, 4, 6, 9, 11, 24, 46, 70, 94, 108, 138, 197, 209 Pulmonary Valve, 111, 197 Pulsation, 174, 197 Pulse, 150, 187, 190, 197 Purines, 197, 201 Putrefaction, 174, 197 Pyrimidines, 197, 201 Q Quality of Life, 37, 197 R Radial Artery, 102, 198 Radiation, 169, 172, 173, 174, 181, 182, 198, 209 Radiation therapy, 172, 181, 182, 198, 209 Radical prostatectomy, 118, 198 Radioactive, 178, 179, 181, 182, 187, 189, 198, 209 Radioimmunoassay, 80, 198 Radiolabeled, 182, 198, 209 Radiological, 191, 198 Radiology, 32, 35, 102, 198 Radiotherapy, 159, 182, 198, 209 Randomized, 13, 18, 23, 26, 53, 63, 64, 168, 198 Randomized clinical trial, 23, 198 Reaction Time, 104, 198 Reagent, 111, 178, 181, 198 Receptor, 20, 29, 32, 39, 40, 94, 99, 151, 154, 168, 198, 201 Recombinant, 7, 23, 94, 107, 198, 199 Recombinant Proteins, 7, 199 Recombination, 174, 199 Rectovaginal Fistula, 102, 199 Rectum, 163, 173, 174, 179, 196, 199 Recurrence, 47, 199 Red blood cells, 63, 92, 171, 177, 199 Refer, 1, 159, 163, 175, 189, 199, 206 Reflex, 172, 188, 199 Regimen, 16, 168, 199, 200 Regurgitation, 176, 199
Remission, 199 Renal Dialysis, 96, 199 Renal failure, 16, 114, 119, 199 Renal pelvis, 42, 199 Renal Replacement Therapy, 96, 199 Reperfusion, 19, 199 Reperfusion Injury, 199 Respiration, 160, 187, 199 Respiratory distress syndrome, 28, 29, 199 Retreatment, 63, 200 Retropubic, 118, 119, 196, 198, 200 Retropubic prostatectomy, 119, 198, 200 Retrospective, 27, 200 Retrospective study, 27, 200 Retroviral vector, 174, 200 Reversion, 160, 200 Rheumatic Heart Disease, 56, 200 Rheumatoid, 84, 105, 163, 200 Rheumatoid arthritis, 105, 163, 200 Ribose, 151, 200 Risk factor, 13, 19, 23, 24, 32, 53, 109, 110, 168, 200 Rodenticides, 149, 200 S Saline, 96, 200 Saliva, 7, 21, 23, 200 Salivary, 7, 21, 23, 27, 200 Salivary glands, 7, 27, 200 Salivary Proteins, 7, 23, 200 Saphenous, 165, 200 Saphenous Vein, 165, 200 Screening, 18, 42, 69, 110, 162, 191, 200 Secretion, 177, 180, 186, 187, 200, 201 Secretory, 21, 200 Seizures, 23, 192, 200 Semen, 196, 201 Semisynthetic, 162, 201 Sensibility, 153, 201 Sepsis, 12, 20, 69, 108, 201 Sequence Homology, 10, 201 Sequencing, 7, 194, 201 Serine, 10, 95, 104, 105, 107, 112, 160, 162, 182, 196, 201, 206, 207 Serologic, 179, 201 Serous, 170, 201 Serum, 32, 37, 39, 56, 70, 94, 152, 153, 163, 182, 183, 198, 201 Serum Albumin, 32, 56, 198, 201 Shock, 201, 207 Side effect, 9, 10, 15, 106, 118, 125, 139, 152, 158, 201, 206 Signal Transduction, 154, 201
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Sinusitis, 66, 201 Skeletal, 187, 201 Small intestine, 162, 168, 178, 181, 202, 207, 208 Smooth muscle, 153, 177, 182, 189, 202, 204 Sneezing, 202, 203 Social Environment, 197, 202 Social Support, 16, 202 Sodium, 5, 92, 96, 202, 208 Sodium Channels, 202, 208 Soft tissue, 158, 202 Solvent, 175, 190, 202 Specialist, 141, 167, 202 Species, 13, 92, 100, 106, 107, 175, 178, 185, 186, 187, 201, 202, 204, 206, 207, 208, 209 Specificity, 14, 17, 32, 50, 152, 202 Spectrophotometry, 32, 202 Spectroscopic, 11, 184, 202 Spectrum, 186, 202 Spermatozoa, 151, 201, 202 Sphenoid, 161, 190, 197, 202 Spinal cord, 156, 159, 161, 162, 168, 172, 174, 188, 199, 202, 204 Spinous, 171, 203 Spirochete, 203, 204 Spleen, 102, 178, 183, 203 Stabilization, 192, 203 Staging, 119, 203 Stasis, 101, 194, 203, 208 Stem Cells, 171, 203 Stent, 115, 203 Sterile, 102, 203 Steroids, 165, 203 Stimulant, 177, 203 Stimulus, 168, 171, 198, 199, 203, 205 Stomach, 151, 168, 171, 174, 178, 181, 202, 203 Stool, 163, 179, 203 Strand, 194, 203 Streptococci, 203 Streptokinase, 94, 203 Stress, 16, 119, 165, 190, 195, 200, 203 Stress incontinence, 119, 203 Subacute, 5, 180, 201, 203 Subarachnoid, 43, 203 Subclinical, 180, 200, 204 Subcutaneous, 52, 168, 204 Subspecies, 202, 204 Substance P, 171, 186, 200, 204 Substrate, 9, 13, 21, 98, 100, 112, 113, 114, 170, 204
Suction, 173, 204 Sulfates, 9, 204 Sulfuric acid, 204 Suspensions, 43, 204, 207 Sympathetic Nervous System, 188, 204 Symphysis, 162, 196, 204 Symptomatic, 53, 204 Synergistic, 103, 204 Syphilis, 139, 160, 204 Systemic lupus erythematosus, 47, 52, 56, 57, 111, 154, 155, 163, 204 Systolic, 178, 204 T Tachycardia, 173, 204 Theophylline, 41, 197, 204 Therapeutics, 11, 16, 62, 127, 205 Thermal, 167, 189, 194, 205 Thigh, 172, 205 Thoracic, 37, 102, 205 Thoracic Surgery, 37, 102, 205 Threonine, 14, 201, 205 Threshold, 178, 205 Thrombin, 8, 9, 10, 13, 19, 20, 21, 25, 27, 29, 34, 36, 39, 40, 41, 53, 59, 68, 74, 82, 95, 97, 98, 100, 104, 105, 106, 109, 112, 113, 155, 172, 173, 193, 196, 205 Thrombocytes, 194, 205 Thrombocytopenia, 12, 22, 51, 63, 106, 111, 205 Thromboembolism, 6, 9, 19, 24, 38, 44, 53, 57, 59, 205 Thrombolytic, 8, 94, 203, 205 Thrombolytic Therapy, 203, 205 Thrombomodulin, 20, 26, 82, 100, 108, 196, 205 Thrombopenia, 155, 205 Thrombophilia, 14, 26, 205 Thrombophlebitis, 9, 138, 205 Thromboplastin, 36, 118, 197, 205 Thrombosed, 194, 205 Thromboses, 57, 155, 205 Thyroxine, 152, 205 Ticks, 23, 205 Ticlopidine, 17, 88, 205 Tissue Plasminogen Activator, 8, 19, 94, 206 Tolerance, 94, 206 Tomography, 158, 184, 206 Tonicity, 182, 206 Tooth Preparation, 151, 206 Torsion, 180, 206 Toxaemia, 195, 206
222
Anticoagulants
Toxic, iv, 7, 179, 188, 206 Toxicity, 11, 168, 186, 206 Toxicology, 134, 206 Toxin, 170, 206 Transfection, 158, 174, 206 Transient Ischemic Attacks, 33, 84, 206 Translational, 19, 24, 206 Translocation, 162, 171, 206 Transplantation, 64, 118, 179, 206 Transurethral, 196, 206, 207 Transurethral resection, 196, 206 Transurethral Resection of Prostate, 196, 207 Trauma, 6, 65, 102, 172, 188, 207 Trypsin, 27, 95, 103, 104, 151, 162, 170, 207, 209 Tryptophan, 163, 207 Tuberculosis, 155, 183, 207 Tumour, 94, 174, 207 Tunica, 169, 187, 207 U Ulceration, 194, 207 Ultrafiltration, 37, 114, 176, 207 Unconscious, 153, 207 Uremia, 199, 207 Urethra, 196, 206, 207 Urinary, 102, 179, 196, 200, 206, 207 Urinary Fistula, 102, 207 Urinary tract, 207 Urine, 9, 36, 149, 158, 168, 175, 179, 182, 196, 199, 203, 207 Urokinase, 8, 94, 105, 112, 207 Uterus, 165, 173, 195, 207 V Vaccines, 207, 208 Vagina, 167, 199, 207 Valproic Acid, 10, 208 Valves, 7, 46, 110, 111, 194, 200, 208 Vasculitis, 139, 208
Vasodilator, 159, 168, 177, 208 Vasomotor, 171, 208 Vein, 4, 6, 9, 11, 58, 68, 108, 153, 156, 180, 181, 189, 200, 205, 208 Vena, 70, 208 Venereal, 204, 208 Venom, 48, 51, 67, 208 Venous blood, 159, 161, 208 Venous Insufficiency, 194, 208 Venous Thrombosis, 9, 19, 24, 30, 33, 46, 52, 94, 106, 108, 119, 206, 208, 209 Ventricle, 101, 186, 197, 204, 208 Ventricular, 6, 208 Ventricular Dysfunction, 6, 208 Venules, 158, 170, 208 Vertebral, 33, 208 Veterinary Medicine, 133, 208 Villi, 208 Villous, 22, 208 Viral, 165, 208 Virulence, 156, 206, 208 Virus, 26, 181, 193, 200, 208, 209 Vitro, 8, 9, 107, 177, 209 Vivo, 9, 22, 37, 74, 107, 209 W Warfarin, 3, 5, 13, 16, 17, 24, 27, 34, 37, 46, 56, 65, 71, 74, 80, 88, 97, 113, 122, 209 White blood cell, 154, 183, 184, 188, 189, 193, 209 Wound Healing, 106, 184, 209 X Xenograft, 153, 209 X-ray, 21, 158, 160, 165, 173, 182, 189, 198, 209 X-ray therapy, 182, 209 Z Zoster, 46, 209 Zymogen, 14, 99, 162, 196, 209
223
224
Anticoagulants
