WARFARIN 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., 1960Warfarin: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-84238-8 1. Warfarin-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 warfarin. 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 WARFARIN ................................................................................................ 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Warfarin........................................................................................ 4 E-Journals: PubMed Central ....................................................................................................... 41 The National Library of Medicine: PubMed ................................................................................ 42 CHAPTER 2. NUTRITION AND WARFARIN ...................................................................................... 87 Overview...................................................................................................................................... 87 Finding Nutrition Studies on Warfarin ...................................................................................... 87 Federal Resources on Nutrition ................................................................................................... 91 Additional Web Resources ........................................................................................................... 91 CHAPTER 3. ALTERNATIVE MEDICINE AND WARFARIN ................................................................ 97 Overview...................................................................................................................................... 97 National Center for Complementary and Alternative Medicine.................................................. 97 Additional Web Resources ......................................................................................................... 107 General References ..................................................................................................................... 114 CHAPTER 4. DISSERTATIONS ON WARFARIN ................................................................................ 115 Overview.................................................................................................................................... 115 Dissertations on Warfarin ......................................................................................................... 115 Keeping Current ........................................................................................................................ 115 CHAPTER 5. CLINICAL TRIALS AND WARFARIN .......................................................................... 117 Overview.................................................................................................................................... 117 Recent Trials on Warfarin ......................................................................................................... 117 Keeping Current on Clinical Trials ........................................................................................... 120 CHAPTER 6. PATENTS ON WARFARIN........................................................................................... 123 Overview.................................................................................................................................... 123 Patents on Warfarin................................................................................................................... 123 Patent Applications on Warfarin............................................................................................... 133 Keeping Current ........................................................................................................................ 139 CHAPTER 7. BOOKS ON WARFARIN .............................................................................................. 141 Overview.................................................................................................................................... 141 Book Summaries: Online Booksellers......................................................................................... 141 The National Library of Medicine Book Index ........................................................................... 141 Chapters on Warfarin ................................................................................................................ 142 CHAPTER 8. PERIODICALS AND NEWS ON WARFARIN ................................................................ 145 Overview.................................................................................................................................... 145 News Services and Press Releases.............................................................................................. 145 Newsletter Articles .................................................................................................................... 149 Academic Periodicals covering Warfarin ................................................................................... 150 CHAPTER 9. RESEARCHING MEDICATIONS .................................................................................. 151 Overview.................................................................................................................................... 151 U.S. Pharmacopeia..................................................................................................................... 151 Commercial Databases ............................................................................................................... 152 Researching Orphan Drugs ....................................................................................................... 152 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 157 Overview.................................................................................................................................... 157 NIH Guidelines.......................................................................................................................... 157 NIH Databases........................................................................................................................... 159 Other Commercial Databases..................................................................................................... 161 APPENDIX B. PATIENT RESOURCES ............................................................................................... 163
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Overview.................................................................................................................................... 163 Patient Guideline Sources.......................................................................................................... 163 Finding Associations.................................................................................................................. 165 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 167 Overview.................................................................................................................................... 167 Preparation................................................................................................................................. 167 Finding a Local Medical Library................................................................................................ 167 Medical Libraries in the U.S. and Canada ................................................................................. 167 ONLINE GLOSSARIES................................................................................................................ 173 Online Dictionary Directories ................................................................................................... 173 WARFARIN DICTIONARY ........................................................................................................ 175 INDEX .............................................................................................................................................. 239
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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 warfarin 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 warfarin, 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 warfarin, 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 warfarin. 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 warfarin, 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 warfarin. 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 WARFARIN Overview In this chapter, we will show you how to locate peer-reviewed references and studies on warfarin.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and warfarin, 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 “warfarin” (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: •
Managing Patients on Warfarin Therapy: A Case Report Source: SCD. Special Care in Dentistry. 21(3): 109-112. May-June 2001. Contact: Available from Special Care Dentistry. 211 East Chicago Avenue, Chicago, IL 60611. (312) 440-2660. Summary: Coagulotherapy is a common therapeutic regimen most frequently utilizing the drug called warfarin. This therapy may have important dental ramifications. As understanding of the mechanisms of action and drug interactions may help avoid problems. Questions commonly arise as to what dental procedures may be safely considered when a patient is on anticoagulant therapy. This article offers a case report that illustrates some of the dental and oral health concerns for managing patients on warfarin therapy. Coagutherapy level is measured in values of the International
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Normalized Ratio (INR). Any question about the appropriateness of dental procedures should be referred to the physician prescriber of the anticoagulant therapy. Generally, controlling bleeding is less of a problem than the management of thrombi (blood clots) and vascular occlusion (blockage) from decreased coagutherapy. The case presented includes the situation where INR reached a critical value as the result of drug interactions (antibiotics) and miscommunications. The authors remind readers that dental treatment for patients on anticoagulant therapy should be considered on an individual basis in consultation with the patient's physician to determine a level of anticoagulation that will provide minimum thrombosis (blood clot) risk and yet achieve workable hemostasis for the dental procedure. 3 tables. 27 references. •
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).
Federally Funded Research on Warfarin The U.S. Government supports a variety of research studies relating to warfarin. 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. 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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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 warfarin. 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 warfarin. The following is typical of the type of information found when searching the CRISP database for warfarin: •
Project Title: ALCOHOL REDUCTION IN MEDICAL ILLNESSES:HCV AS PROTOTYPE Principal Investigator & Institution: Dawson, Neal V.; Medicine; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): Alcohol use is discouraged or contraindicated for patients with a variety of medical illnesses. For many diseases directly caused by alcohol, the use of alcohol may be associated with recurrent symptoms shortly after its consumption, e.g., pancreatitis or gastritis, and the prohibition against alcohol is straightforward. However, for many chronic diseases, the use of alcohol is not associated with any short-term symptoms or sequelae. The course of these chronic diseases (or their treatments) among non-abusing/nondependent patients can be adversely affected by even moderate alcohol use, e.g., chronic hepatitis, (nonalcoholic) cirrhosis, severe diabetes, or the use of the 'blood thinner', warfarin. Chronic Hepatitis C virus (HCV) infection is a prototypical example of a disease in which alcohol use tends to cause no symptoms. Even moderate chronic alcohol use can be associated with an increased likelihood of cirrhosis and liver cancer. HCV infection rates and prognosis are related to alcohol use in multiple ways. Alcohol use during HCV treatment is associated with a decreased likelihood of viral clearance. Long-term alcohol use may increase the proliferation of HCV and the associated liver damage even with moderate alcohol consumption. Greatly reducing or eliminating alcohol use may importantly enhance the prognoses of patients, even if they are not candidates for specific HCV treatments. Despite having diagnoses that warrant abstinence from alcohol, many patients continue to drink alcohol. Little is known about why patients continue to consume alcohol in the face of diagnoses that warrant a reduction in use or abstinence. The current study is designed to determine factors that lead to continuing alcohol intake among alcohol nonabusing/nondependent patients who are advised to stop drinking by health care providers. In Phase 1, focus groups (patients and providers) will be used to discover issues that may be associated with continued drinking. In Phase 2, questionnaire items will be developed based on the data gleaned from Phase 1. The potential pool of items will be administered to 10 patients per item and factor analyzed. In Phase 3, the items retained from the pool of potential items will be used to create a questionnaire that will be tested for its ability to predict alcohol reduction or cessation. Since alcohol use is common in the U.S. and since most patients who currently have HCV are not candidates for treatment, abstinence from alcohol use represents a major opportunity to prevent a decline in the health and quality of life of patients with HCV and similar diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ANTICOAGULATION POST-FONTAN/CLOSURE OF ASDS Principal Investigator & Institution: Mccrindle, Brian W.; Hospital for Sick Chldrn (Toronto) 555 University Ave Toronto,
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Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 31-AUG-2006 Summary: (provided by applicant) Patient-related research in heart problems in children has been of limited quality, because of lack of collaboration and emphasis on information provided in medical charts. Important problems remain controversial and unsolved. The Fontan operation is designed for patients who have only one pumping chamber, and guides blood from the major veins returning to the heart directly into the lung arteries, with the pumping chamber reserved to pump blood into the arteries of the body. Afterwards, blood flows differently and more slowly in the veins and lungs, and clots may form, which can cause strokes. The proposed study aims to determine the risk of clots and the best way to prevent them. The study will consist of a review medical charts on a large number of patients who have had Fontan to help determine the risk of clots. For patients who will have Fontan, they will be enrolled in a study where they will be randomly assigned to different types of medications to prevent clots, which will be compared. For patients who have already had the Fontan, they will be enrolled in a similar study where they will randomly assigned to either aspirin or a medication called warfarin. In both the studies, the patients will have regular check-ups and tests for a two year period to see if clots occur and which type of medicine best prevents the clots. Atrial septal defects, or holes between the two collecting chambers of the heart, can lead to heart failure and heart rhythmn problems. They can be closed with surgery, or by placing a special patch or device with a catheter. The proposed study aims to determine whether closure is better with surgery or the catheter method, and whether there are any differences in closure with different types of catheter devices. The study will review medical charts of children who have had closure of these holes, and compare surgery and catheter methods. A second part of the study will enroll children with holes which need to be closed, and randomly assign them to either surgery or the catheter method. For patients assigned to the catheter method, they will be further randomly assigned to one of two types of catheter devices. Comparisons will be made between surgery and the two catheter methods regarding the completeness of closure and complications. A further analysis will look at patient preferences and the costs for these different types of procedures, to help determine the best way to close these holes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANTIPHOSPHOLIPID ANTIBODIES AND STROKE Principal Investigator & Institution: Levine, Steven R.; Professor; Neurology; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2000; Project Start 27-SEP-1993; Project End 30-JUN-2004 Summary: We propose to continue to study the significance of antiphospholipid antibodies (aPL), hematologic markers for increased risk of vascular thrombo-occlusive events, in ischemic stroke using the cost-effective and efficient strategy of collaborating with the WARSS (Warfarin Aspirin Recurrent Stroke Study) cohort--the continuation of the WARSS-APASS (Antiphospholipid Antibodies in Stroke Study) Collaborative Study. Based on current WARSS enrollment, 5 years of funding will be necessary to complete enrollment, follow-up, study closeout, and data analyses. aPL, seen in approximately 20% of first ischemic stroke patients in the WARSS cohort, may be a marker for increased risk of subsequent thrombo-occlusive events, including recurrent stroke. We wish to continue to combine scientific interests of WARSS and APASS. WARSS is a randomized and double-blind secondary stroke and death prevention trial comparing aspirin and warfarin in two treatment arms. The details of the WARSS-APASS collaboration have been worked out and use a mutually beneficial and highly cost effective strategy to assess aPL status in all WARSS patients. We are testing the
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hypothesis that a positive aPL status in the WARSS cohort will confer a higher risk of subsequent thrombo-occlusive events compared to WARSS patients who do not have aPL and who are matched to treatment arm. APASS requests continued support to obtain aPL status at baseline on all WARSS enrolled subjects and to document all thrombo-occlusive events. aPL status will also be documented yearly and at the time of a recurrent thrombo-occlusive event for all aPL(+) patients and one matched aPL(-) patient for each aPL(+) patient to ensure blinding of aPL status at each of the WARSS clinical centers. In addition, we believe that the important information obtained from this study could lead to a treatment trial potentially resulting in improved and more cost-effective health care for the subset of patients with stroke and aPL. This number is estimated to be at least 40,000 people per year in the United States. The cost to care for these patients, just in terms of acute health care dollars spent, is over $30 million, based on the Relative Index Scale. One could extrapolate similarly for myocardial infarction, deep venous thrombosis, systemic thromboembolic events and fetal loss (other thrombo-occlusive events linked to aPL). The number of people in the United States per year with this potentially treatable autoimmune-mediated syndrome is a major cause for concern and clearly demonstrates a need for further epidemiological study. There are benefits of linking APASS to WARSS, regardless of whether WARSS turns out to be a negative or a positive clinical trial for treatment differences. In addition, this is an opportunity to pioneer a new level of collaborative effort with great potential to benefit stroke victims, contribute significantly to our basic knowledge about stroke mechanism and save tax dollars. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ATRIAL FIBRILLATION INCIDENCE, RISK FACTORS AND GENETICS Principal Investigator & Institution: Heckbert, Susan R.; Associate Professor; Epidemiology; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2006 Summary: (provided by applicant): The goal of this research is to assess the safety of commonly used medications in relation to the risk of incident atrial fibrillation (AF), and to assess the association of several genetic polymorphisms with stroke risk after AF onset. Several lines of evidence suggest that both beta-blockers and ACE inhibitors may prevent or inhibit the atrial electrical remodeling that allows AF to become established and maintained. Withdrawal of these medications may be associated with increased risk of AF in individuals at risk. Genetic polymorphisms that promote thrombosis are associated with an increased risk of venous thrombosis, and in some studies, with arterial thrombosis including stroke or myocardial infarction. Although several recently published trials indicate that warfarin or aspirin treatment of patients with AF decreases the risk of stroke, little is known about the risk of stroke as a complication of AF in relation to genetic variants that affect clotting. The proposed project will build on successful population-based studies of myocardial infarction and stroke at Group Health Cooperative (GHC), a large non-profit health maintenance organization. Detailed information from the GHC computerized pharmacy database on the timing of medication use among approximately 1500 incident AF cases and 1750 controls with medically treated hypertension will permit us to assess the risk of incident AF associated with the use or recent stopping of beta-blockers or ACE inhibitors. This project will collect DNA samples on a population-based inception cohort of approximately 855 AF patients, and will examine the risk of stroke in relation to genetic variants known to affect coagulation. The main tasks of the proposed project are: 1)
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identification of cases with incident AF and controls; 2) review of outpatient and inpatient medical records to assess eligibility and collect information on risk factors and medical history; 3) classification of medication use over time; 4) for AF patients, telephone interview and collection of blood samples; 5) blood specimen processing, DNA extraction, and genotyping; and 6) data analysis of the associations of medication use and genotype with AF onset and stroke complications. This project will contribute important information about drug safety and will incorporate advances in molecular biology to study AF and its complications, problems of considerable public health importance in the elderly. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CE-MS OF BIOLOGICAL SUBSTANCES USING CHIRAL POLYMERS Principal Investigator & Institution: Shamsi, Shahab A.; Chemistry; Georgia State University University Plaza Atlanta, Ga 30303 Timing: Fiscal Year 2002; Project Start 01-FEB-2002; Project End 31-JAN-2007 Summary: In many health related fields the resolution and structural identification of enantiomeric compounds are necessary steps for studying racemic drug interactions. The coupling of capillary electrophoresis (CE) to mass spectrometry (MS) using conventional micelles [above the critical micelle concentration (CMC)] is very difficult if not impossible. Preliminary data in our laboratory indicates that the uses of polymerized surfactant or micelle polymers provide one possible solution for this difficult coupling. This is because of many positive attributes of micelle polymers which includes zero CMC, lower surface activity, low volatility and function as suitable separation media even at lower concentrations of pseudophases. These are some benefits that produce a stable electrospray. This proposal is aimed at synthesis and development of new class of chiral anionic and cationic micelle polymers for use in chiral electrokinetic chromatography (EKC)-MS. Depending on the polarity of the chiral analytes two different approaches are proposed for the success of chiral EKC-MS. The first approach involves simply the use of chiral micelle polymers as additives in EKCMS or partial-filling EKC-MS for the separation of very polar and charged compounds. For the chiral separation and MS detection of very hydrophobic and neutral chiral molecules that have large capacity factors and low ionization efficiency, a second approach is proposed. This involves the use metal complexes of anionic micelle polymers as reagents for the coupling of ligand exchange-EKC to coordination ion mass spectrometry. The combined use of metal with chiral micelle polymers will not only provide faster and efficient chiral separations of hydrophobic molecules but will also help in efficient transport of complexes to the gas phase for electrospray ionization. In addition, a dual chiral selector system, capillary electrochromatography (CEC)-EKC-MS is also proposed for analytes with multiple chiral centers. Following studies on the optimization of chiral EKC-MS of wide variety of chiral compounds, two different methods will be developed to improve the concentration sensitivity of CE-MS. The first methodology includes a new approach in developing an automated capillary isotachophoresis in conjunction with chiral EKC to improve the sample loadability of the chiral analytes which will benefit analysis of chiral metabolites at therapeutic levels without sample preparation. Besides this, a second methodology involves investigation on chiral EKC-MS-MS for trace level detection and understanding of the metabolic pathways of patients undergoing warfarin and thalidomide therapy for various diseases. We realize that the application of this valuable technology of chiral EKC-MS and chiral EKC-MS-MS will lead to the significant advances across several scientific disciplines. The strategies described in this proposal may signal a new beginning of a
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highly efficient and information rich hyphenated technology, which will enable our research group and others to acquire significant high throughput screening methods for analysis of chiral drugs than ever previously experienced. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CHROMATOGRAPHIC AUTOMATION OF IMMUNOASSAYS Principal Investigator & Institution: Hage, David S.; Associate Professor; Chemistry; University of Nebraska Lincoln 14Th and R Sts Lincoln, Ne 68588 Timing: Fiscal Year 2001; Project Start 13-AUG-1991; Project End 31-MAR-2005 Summary: APPLICANT'S The free, or non-bound, form of many drugs and hormones in blood or serum is of great interest since this is believed to represent the active form of these compounds, making it the ideal analytical tool for patient diagnosis or treatment. But there is currently no general, fast approach for measuring free solute levels within the body. Recent work with L-thyroxine and R/S-warfarin has demonstrated that free solute measurements are possible by using millisecond-scale affinity extractions and online chromatographic immunoassays. This proposal seeks to further develop and refine this approach for its use with other analytes. The first part of this project will consider several new applications for these assays (e.g., therapeutic monitoring and pharmacological studies). Alternative assay formats will also be examined, such as 1) the use of LC/MS or near-infrared fluorescent labels for detection, 2) the use of monolithic supports in affinity extraction columns, 3) the use of aptamers as ligands I for these columns, and 4) the development of HPLC displacement or immunometric assays for quantitating the extracted drugs and hormones. The second part of this project will use computer simulations and model systems to optimize these methods. Specific items to be examined will include: 1) the degree of extraction that is needed for free drug/hormone analysis by affinity extraction, 2) the effect on these assays when multiple binding agents for a solute are in a sample, and 3) the affinities and dissociation kinetics that are needed for ligands used in such assays. The last section will examine the interactions of new analytes with their binding agents in serum or plasma to aid in the development of the free solute assays. This will involve the use of several affinity methods based on HPLC, CE or LC/MS to 1) identify' the agents in serum or plasma that interact with each new candidate for free fraction measurements, 2) determine the equilibrium constants for these interactions, and 3) estimate the rare constants for these processes (e.g., the rare of analyte release from its binding agents). The result of this work should be the creation of new, more rapid tools for determining free drug or hormone levels, providing a better means for studying how such compounds behave and interact within our bodies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CYTOCHROME P450 SUBSTRATE SITING AND MOTION Principal Investigator & Institution: Mcdermott, Ann E.; Professor; Chemistry; Columbia Univ New York Morningside 1210 Amsterdam Ave, Mc 2205 New York, Ny 10027 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-AUG-2003 Summary: Rationalization and prediction of hydroxylation products of cytochrome P450 is crucial for understanding the mechanism of this enzyme and for understanding drug metabolism, but remains generally enigmatic. We propose studies of orientation of substrates in the enzyme pocket, and motion of substrates in the enzyme pocket, by new magnetic resonance methods. A longstanding hypothesis states that, counter to typical enzymological dogma, many substrates bound to the active site of (mammalian or
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prokaryotic) cytochrome P450 rotate rapidly on the timescale of enzymatic turnover; this putative motion might actually be reasonable and even needed for turnover, since the substrate pocket appears to be rather hydrophobic and chemically "featureless". If this motion does indeed occur, it would have important implications for understanding hydroxylation preferences. We have performed preliminary studies of substrate siting and motion for adamantane bound to the resting state of CP450cam, using deuterium magic angle spinning (MAS) SSNMR spectroscopy. These preliminary data support the hypothesis of extensive motion. On this preliminary basis we propose to conduct more detailed studies with medicinally relevant systems. In this preliminary study, competitive displacement and Curie-law temperature dependence of isotropic shifts were used to verify location at the active site. Simulation of deuterium spinning sideband intensities allowed us to determine the strengths of the electron-nuclear dipolar hyperfine coupling, the strength of the effective deuterium quadrupolar splitting (which serves as measure of local motion) and the Euler angles describing the mutual orientation of the dipolar and quadrupolar tensors. Simulations of analogous data from model compounds are reported in a recent publication; RMS agreements of approximately 5 percent are possible, and the simulations are used to determine distances to a precision of 0.5 Angstrom units up to a maximum "capture radius" of 7 Angstrom units, and angles were determined to within 20 degrees. Simulations of the data for enzyme-bound adamantane indicated an average metal-deuterium distance of 6.0 (+/- 0.2) Angstrom units and clear-cut evidence of a rapid high- symmetry motion. Computational and experimental improvements for analysis of the line-shape and spinning side-band intensities are proposed. We propose to characterize substrate motion for additional substrates (camphor, benzene, toluene, xylene, nicotine and warfarin), and an additional stable intermediate of the enzymatic cycle. Substrate geometry relative to the heme and substrate motion will be studies for the mammalian P450 enzyme using a membrane-mimic environment (DMPC/DHPC bicelles); information about substrate geometries is unavailable from crystallographic studies at present. Studies involving microbial detoxification enzymes with similar chemical mechanisms are also planned. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DETERMINANTS OF INDIVIDUAL RESPONSIVENESS TO DRUGS Principal Investigator & Institution: Wilkinson, Grant R.; Professor of Pharmacology; Pharmacology; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 01-DEC-1982; Project End 30-JUN-2007 Summary: (provided by applicant): The overall objective of this continuation Program Project remains the definition of determinants and the elucidation of mechanisms responsible for interindividual variability in response following drug administration in humans. The basic and clinical knowledge derived from the proposed research will provide a basis for the rational development and safe use of drugs. The Program Project's goals will be achieved by a synergistic group of investigators with expertise and interests in medicine, pharmacology, biochemistry, molecular biology and genetics. The focus of Project 20 is on cytochrome P4503A (CYP3A) which is involved in the metabolism of over 50 percent of drugs and is an important determinant of their firstpass metabolism following oral administration. Studies are proposed to investigate why the in vivo metabolism of various CYP3A substrates does not appear to correlate with each other despite the involvement of a common enzyme. Genetic factors contributing to interindividual variability in CYP3A activity will also be investigated in twin- and population studies. Project 21 will investigate whether pre-prescription genotyping of
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an individual patient will improve drug efficacy and safety. The anticoagulant warfarin, which has a narrow therapeutic index and is variably metabolized by polymorphic cytochrome P4502C9, will be used to test this possibility. The central theme of Project 22 is genetic variability in hepatic efflux transporters and orphan nuclear receptors involved in the transcription of cytochrome P4503A and the transporters. In addition to discovering novel polymorphisms, the functional consequences of such variability will also be assessed both in vitro and in vivo. Project 23 is directed towards the in vivo pharmacological modulation in humans of the function of the membrane efflux transporter MDR1 (P-glycoprotein) that is a determinant of the disposition of many drugs. The feasibility of using a potent and specific MDR1 inhibitor to increase tissue and systemic drug bioavailability will be specifically addressed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DISORDERED BLOOD COAGULATION IN SICKLE CELL DISEASE Principal Investigator & Institution: Ataga, Kenneth I.; Medicine; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2007 Summary: (provided by applicant): There is convincing evidence to show activation of both blood coagulation and platelets in patients with SCD. For example, plasma samples obtained at both steady state and during painful crisis exhibit high levels of thrombin generation, depletion of anticoagulant proteins, and abnormal activation of the fibrinolytic system. Similarly, exposure of such surface markers as CD62P and CD40L, along with increased circulating levels of thrombospondin represents strong evidence of platelet activation. Over and above its effects on the cleavage of fibrinogen and its ability to activate platelets, the increase in thrombin generation, with its wide-ranging effects on endothelial cells and blood vessels, could play an important role in the pathophysiology of SCD. The overall hypothesis that the investigators seek to test in this proposal is that activation of the coagulation system, along with the adhesive and/or inflammatory responses that are initiated by platelet activation, are important contributors to the pathophysiology of vasoocclusion, the hallmark of SCD. The model on which they have chosen to test this hypothesis is the sickle cell leg ulcer, a chronic, painful, and often disabling complication for which there is to date, no effective therapy. In Specific Aim 1, they will conduct a randomized, single-blind trial of low intensity anticoagulation. They hope that by normalizing thrombin generation and subsequently decreasing platelet activation, they will promote the healing of these leg ulcers. In Specific Aim 2, they will employ eptifibatide (EPF), a known inhibitor of the glycoprotein Ilb/Illa receptor, to evaluate the adhesive and inflammatory contributions of platelets to the pathophysiology of SCD. Throughout all aspects of this proposal, they will collect extensive data that they hope will enable them to answer the primary question inferred by their overall hypothesis - i.e., is the "hypercoagulability" observed in patients with SCD a primary cause of the vasoocclusion or is it simply a secondary event that is observed in this clinical setting. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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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 2001; 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: FASEB K&SYNTHESIS,STRUCTURE,FUNCTION
CONFERENCE:VITAMIN
Principal Investigator & Institution: Lian, Jane B.; Professor; Federation of Amer Soc for Exper Biology Bethesda, Md 208143998 Timing: Fiscal Year 2001; Project Start 04-AUG-2001; Project End 03-AUG-2002 Summary: (provided by applicant) This proposal is for partial support of a conference on Vitamin K and Vitamin K-Dependent Proteins that is being held under the auspices of the Federation of American Scientists for Experimental Biology (FASEB) from August 4-9, 2001, at the Vermont Academy in Saxtons River, VT. This conference will represent multi-disciplinary fields spanning nutrition, application of vitamin K for intervention of osteoporosis and cardiovascular disorders, blood coagulation, skeletal development, and the conotoxin Gla neuroactive peptides. Fundamental biochemical and molecular mechanisms provide the basis for assimilating the common regulatory parameters of vitamin K mediated biological activity. Knowledge of the vitamin K dependent carboxylase, the structural requirements of Gla peptide substrate and enzyme interactions, regulation of propeptide and mature protein synthesis, the requirements for vitamin K, and interactions of calcium bound-Gla domains with phospholipid membrane components that reflect the shared properties of the vitamin K-dependent proteins will be evaluated. The meeting will focus on the most recent developments in vitamin K research. Participation will be limited to 150 applicants who will be selected on the basis of expertise and ability to contribute to a stimulating and productive
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meeting. The conference will consist of nine scientific sessions, two afternoon roundtable discussions, and poster sessions. The major session topics will be: (1) vitamin K and nutrition, (2) structure-function relationships of vitamin dependent proteins and membrane interactions, (3) molecular mechanisms mediating gen expression/developmental regulation of vitamin k dependent proteins with aging, (4) matrix Gla proteins and tissue functions, (5) matrix Gla proteins and cardiovascular disease, (6) vitamin K status: skeletal pathophysiologies an therapeutic intervention, (7) the Conotoxin family of Gla neuropeptides and recently discovered Gla containing proteins, (8) the family of vitamin K carboxylase enzymes, (9) vitamin K and warfarin. Exchange of ideas and insights among these investigators from diverse fields will provide the opportunity for new scientific collaboration and new research directions with potential for impact on neurologic, cardiovascular and bone diseases. The program includes leaders in the field and new/junior investigators, postdoctoral fellows, and scientists from Europe and Asia with exciting and unique findings. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FIBRIN AND FIBRINOLYSIS IN THROMBOTIC DISEASE Principal Investigator & Institution: Marder, Victor J.; Clinical Professor of Medicine; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2001 Summary: Project 5 deals with translational research of laboratory observations to the patient, specifically regarding soluble fibrin (SF) measurements in vitro and in patients with hypercoagulable states and novel fibrinolytic and thromboprophylactic treatments. Aim 1 "to asses the in vitro foundation and the diagnostic and prognostic validity of soluble of fibrin measurement in acute and chronic pro-thrombotic states" includes three distinct sections. The first deals with the reactive of derivatives of fibrinogen and fibrin induced and fibrin induced by thrombin, factor XIIIa and plasmin, especially SF, using specific immunologic and functional approaches. The second utilizes this information to acute hypercoagulable syndromes (DIC) in patients with acute sepsis or with multitrauma and in volunteers receiving endotoxin infusion. In the third part, the prognostic importance of SF will be assessed in patients with chronic hypercoagulable states, including those with breast malignancy who are prone to develop DVT and those with acute MI who are predisposed to recurrent MI or coronary death. Aim 2 "to critically evaluate new thromboprophylactic and fibrinolytic therapies" includes three randomized trials. The first extends our observations on central venous catheter thrombi to a clinical trial of low-dose warfarin prophylaxis. Fibrinolytic studies evaluate plasminogen amplification of UK therapy for peripheral arterial occlusion (PAO) and catheter-delivery of UK for DVT in comparison with UK administered intravenously. Some studies are well underway (plasminogen supplementation of UK for PAO), others have been recently initiated (SF structural investigations, prophylaxis of central venous catheter thrombosis, SF studies in patients with DIC, prognostic value of SF for recurrent coronary artery events, and SF as a marker of hypercoagulability in breast malignancy), and one study is in the pilot phase, with plans to initiate a prospective study (catheter versus IV administration of UK for DVT). These translational studies will critically evaluate the role of SF as a diagnostic and prognostic marker for microvascular, arterial and venous thrombotic disease and apply our prior observations to effective prevention of DVT associated with catheters and to thrombolytic management of PAO and DVT. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENETIC DETERMINANTS OF HEMATOMA VOLUME Principal Investigator & Institution: Rosand, Jonathan; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant): Intracerebral hemorrhage (ICH), bleeding into brain parenchyma from an arterial source, is the deadliest form of stroke and, in contrast to ischemic stroke, lacks any well-proved effective therapy. Although the majority of cases of ICH are spontaneous, ICH is also the most feared complication of warfarin, a medication indicated for long-term use in millions of Americans with atrial fibrillation. When associated with warfarin, ICH is even more devastating, with fatality over 50%. This research program aims to identify the genetic predictors of outcome from ICH and from ICH specifically related to warfarin. It will investigate apolipoprotein E genotype (APOE) and the factor XIII Val34Leu polymorphism. The objectives of this proposal are to determine 1) whether APOE predicts large hematoma volume in acute ICK, acute hematoma enlargement, and poor clinical outcome from acute ICH, and 2) whether factor XIII Val34Leu predicts hemorrhage recurrence in survivors of ICH, and is an independent protective factor for outcome from ICH related to warfarin. These objectives will be completed in a carefully characterized cohort of consecutive cases of spontaneous ICH. Because of the rapid growth in the understanding of both the human genome and the molecular basis of coagulation and vessel pathology, this cohort is likely to form the foundation of a powerful, open-ended search for genetic determinants of ICH and serve as a crucial tool for future studies. During the award period, in addition to serving as principal investigator for the proposed studies, Dr. Rosand will complete formal didactic training in research ethics, epidemiology, and biostatistics with a focus on the statistics applied to genetic studies of complex diseases. His mentor will be Dr. Steven M. Greenberg. Drs. James F. Gusella and Walter J. Koroshetz will serve as co-mentors. Upon conclusion of the award, Dr. Rosand, who has completed clinical fellowship training in stroke and critical care neurology, will have acquired the requisite skills to function as an independent investigator with specific expertise in genetic epidemiology. He will be trained to conduct fundamental studies in clinical and molecular epidemiology of acute cerebrovascular disease as well as pivotal clinical trials of novel therapeutic interventions for ICH. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENETIC POLYMORPHISMS IN THE EPOXYGENASE PATHWAY IN HYPERTENSION Principal Investigator & Institution: Dreisbach Iii, Albert W.; Tulane University of Louisiana New Orleans, La New Orleans, La 70112 Timing: Fiscal Year 2002; Project Start 20-SEP-2002; Project End 31-AUG-2007 Summary: Vasoactive arachidonic acid metabolites of the cytochrome P450 (CYP) epoxygenase pathway, the epoxides, have been implicated in animal and human studies of hypertension. The epoxide 11-12 epieicosatrienoic acid (11,12-EET), the putative endothelium derived hyperpolarizing factor (EDHF)is formed by the enzymes CYP2C9, CYP2C8, and converted to its corresponding dihydroxy metabolite (DHET) by soluble epoxide hydrolase (sEH). CYP2C9 and CYP2C8 and sEH exhibit a high prevalence of genetic polymorphisms which may lead to altered levels of epoxides and reduced formation of EDRH in hypertensive patients. The perturbed vasoactive epoxide profile produced by genetic polymorphisms in this pathway may play a mechanistic role in a subgroup of patients with hypertension. Specific Aim 1: We propose to determine the
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prevalence of CYP2C9fC8 and sEH polymorphisms in hypertensive populations including both African Americans and Caucasians and compare these to the prevalence of these polymorphisms in race matched healthy control subjects. Specific Aim 2: We will also measure levels of EETs and DHETs in plasma and urine of patients with hypertension compared to race matched healthy controls for the various genotypes of CYP2C8/C9 and sEH. Specific Aim 3: We will determine whether in vivo CYP2C9 activity as measured by plasma S/R warfarin ratio, correlates with plasma and urine concentrations of eicosanoid metabolites for the various CYP2C9 genotypes in these same groups. Specific Aim 4: We will determine brachial artery reactivity via ultrasound in each of these same genotypic subgroups in race matched hypertensives and controls. The results from these studies will lead to new insights into the role of polymorphisms of the P450 epoxygenase system in cardiovascular regulation. The studies may demonstrate a role of these polymorphisms in some hypertensive populations, but in any case will provide increased understanding of the role of EETs and DHETs in vascular reactivity and blood pressure regulation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETIC RISKS FOR MEDICATION-RELATED HEMORRHAGIC STROKE Principal Investigator & Institution: Greenberg, Steven M.; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2003; Project Start 20-SEP-2003; Project End 30-JUN-2008 Summary: (provided by the applicant): Despite increasing recognition of the efficacy of anti-coagulation for prevention of Thromboembolism, its use remains limited by the risk of Intracerebral Hemorrhage (ICH). Improved understanding of the biological basis of ICH offers the possibility that genetic tests might identify patients at particularly high risk prior to initiation of therapy. Building on the Principal Investigator's studies of genetic risk factors for ICH, we propose a pharmacogenetic investigation of warfarinrelated ICH. This study will be based at five major stroke referral centers: Massachusetts General Hospital; Columbia-Presbyterian Medical Center; Boston Medical Center; Cornell Medical Center; and the University of Michigan Health System. Consecutive ICH patients and matched control subjects will be analyzed for polymorphisms in apolipoprotein-E, the fibrin cross-linking enzyme factor XIII, the cytokine-transforming growth factor-131, and its receptor-associated protein Endoglin, each a gene with suggested links to ICH. A case-control analysis will be used to determine whether the candidate genotypes are associated with the occurrence of warfarin-related ICH. Based on preliminary data suggesting possible genetic determinants of ICH outcome, we will also analyze the ICH cohort, prospectively, for the effects of genotype on hematoma volume, hematoma expansion, patient mortality, and functional status. Parallel analyses will be conducted among patients with Warfarin-related ICH, and no-treatment ICH to determine whether any identified risk factors are specific to hemorrhages that occur with Warfarin. We anticipate that additional candidate genes will continue to emerge during the course of the proposed studies, given rapid growth in our knowledge of both the human genome and the molecular basis of coagulation and vascular pathology. This proposal is thus likely to form the foundation of a powerful, open-ended search for a panel of genetic tests to determine an individual's risk for Warfarin-related ICH. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENOTYPING TO OPTIMIZE INDIVIDUALIZED DRUG THERAPY Principal Investigator & Institution: Stein, C M.; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 01-DEC-1982; Project End 30-JUN-2007 Summary: (provided by applicant): Interindividual variability in drug responsiveness is marked and related to between subject differences in the drug's disposition/pharmacokinetics and/or pharmacodynamics. In turn, variability in drug disposition, generally, reflects the interplay between environmental and genetic factors. With the rapid advances in knowledge about the human genome and recognition that variability at the DNA level is common, an exciting notion of potentially major clinical importance postulates that genetic information about an individual will ultimately allow drug therapy to be "tailored" to that particular patient. Appropriate technology to routinely provide information on single nucleotide polymorphisms (SNPs) and other genetic variability will, undoubtedly, become more available in the near future. However, the validity and potential benefits of a pharmacogenetic strategy, involving pre-prescription genotyping, for the routine therapeutic management of patients has yet to be tested and proven. This Project proposes to investigate this question through the use of warfarin as an index probe of a drug with a narrow therapeutic index and large differences in its metabolism associated with allelic variants of cytochrome P4502C9 (CYP2C9). In Specific Aim 1, studies are proposed in healthy subjects to determine the functional consequences on warfarin?s metabolism of a newly discovered variant CYP2C9*5 that is selectively expressed in African-Americans. By contrast, Specific Aim 2 focuses on the consequences of genetic variability in CYP2C9 associated with the *1, *2, *3 and *5 alleles in European- and African-American patients receiving anticoagulant therapy with warfarin. This observational study will indicate the relationship between a specific CYP2C9 genotype and the optimal warfarin dose in such patients. Subsequently, such information will be used in a prospective, randomized study in Specific Aim 3 to test the hypothesis that initiating warfarin therapy based on an individual patient?s genotype will improve clinical outcome compared to the current standard-care approach based on empirical optimization of the dose. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HUMAN CYP2C MODELS Principal Investigator & Institution: Rettie, Allan E.; Professor and Chair; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: The long-term aim of this research is to understand the structural basis underlying the unique substrate specificities of the human CYP2C enzymes. Enzyme inhibition during polytherapy, particularly for CYP2C9, is a general mechanism underlying severe drug-drug interactions with agents such as warfarin and phenytoin. Adverse drug reactions of this type are a major, but potentially avoidable, drain on health care costs in the US. However, our ability to predict inhibitory drug-drug interactions from data obtained in vitro is limited by the lack of high resolution structures and robust pharmacophore models for these P450 enzymes, as well by complications imposed by the observation of atypical Michaelis-Menten kinetics and Type II inhibitor complex formation. This project addresses these limitations with the following specific aims: Specific Aim 1: Construct new CYP2C CoMFA models by determining the inhibition constants for a series of benzbromarone analogs to determine which features confer strong binding interactions with CYP2C9, CYP2C19 and CYP2C8.
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Specific Aim 2: Determine the effect of pKa and steric factors on strength of type II interactions by measuring binding affinities to CYP2C9 for a series of coumarin-based ligand molecules with and without nitrogen-bearing substituents and with different steric features adjacent to the nitrogen. Specific Aim 3: (a) Determine the structural basis for homotropic cooperative behavior of phenacetin (and pyrene) with human CYP2C9 and CYP2C19 through site-directed mutagenesis, (b) develop complementary NMR approaches to the study of human CYP2C cooperativity. Specific Aim 4: (a) Delineate the role of Arg108 in CYP2C9 substrate selectivity; (b) engineer a soluble, monomeric form of the ultra-stable, iron-nitrogen coordinated Arg108His mutant, and (c) develop histidine scanning mutagenesis and formation of the iron-nitrogen complex as a tool for examining the role of CYP2C9 B-C and F-G loop region mobility in substrate specificity. In this manner, we will bring together organic synthesis, QSAR analysis of Type I and Type II ligands, site-directed mutagenesis, conformational analysis of protein flexibility and, ultimately, crystallography of human CYP2C mutants, to develop an integrated picture of ligand interactions with these important human enzymes that will enable us to assess, in a prospective manner, the potential for inhibitory drug-drug interactions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HUMAN/MEDICAL FACTORS AS PREDICTORS OF THERAPY ADHERENCE Principal Investigator & Institution: Kimmel, Stephen E.; Associate Professor; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 07-SEP-2001; Project End 31-AUG-2006 Summary: (PROVIDED BY APPLICANT) Poor adherence with medication therapy has been estimated to be responsible for more than 5 percent of all hospital admissions, with an associated direct cost exceeding $8 billion. This is a particular problem with drugs that have a narrow therapeutic index. Warfarin is such a drug. If used correctly, warfarin is highly efficacious in preventing thromboembolism (TE) in patients with conditions that put them at risk. However, errors in its use can lead to life-threatening thromboembolic and bleeding complications. In addition, errors can lead to increased medical costs, reduced quality of life, patient dissatisfaction, and discontinuation of a highly efficacious therapy. Because of the numerous conditions that put patients at risk, warfarin is the tenth most commonly prescribed medication in the United States. As a result of this widespread use and the drug?s narrow therapeutic index, warfarin errors are extremely common. Despite our medical knowledge and attendant attempts to control many factors that can affect anticoagulation levels, proper anticoagulation is extremely difficult to maintain. Even in optimal clinical settings, about one-half of all patient time is spent either under-or over-anticoagulated. In our hospital, complications from warfarin are the most commonly reported adverse drug reaction and warfarin is the leading cause of admissions for serious adverse drug events. Even "near misses" can lead to increased medical costs and discontinuation of an otherwise extremely effective therapy. Poor patient adherence with warfarin therapy is often cited as one of the most common errors with the drug. However, the problem with adherence has not been addressed, and no study has rigorously attempted to identify predictors of poor adherence with warfarin. Therefore, the purpose of this study is to determine the human and system factors (both patient and medical practice specific) that lead to errors with warfarin, specifically focusing on adherence. The aims are to perform a prospective cohort study of anticoagulation patients to determine the specific clinical, demographic, health care structural, pill-taking practices, and psychosocial factors associated with poor adherence, and to develop a predictive index that can identify patients at risk for
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medication errors. The hypothesis is that specific clinical and demographic characteristics, psychosocial factors (e.g., poor cognition, passive coping strategies) and variables describing medical practice (e.g., time providers spend with patients, primary care physician support) and medication-taking practices (e.g., reminder systems) will predict poor adherence with warfarin. The ultimate goal of this research is to provide a more complete understanding of the epidemiology of patients' errors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IMPROVING ANTICOAGULATION
ADHERENCE
FOR
DYSLIPIDEMIA
AND
Principal Investigator & Institution: Rudd, Peter; Medicine; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-AUG-2004 Summary: (investigator's abstract): The proposed project seeks to improve the medication adherence and clinical control of ambulatory patients' prescribed treatment for two clinical situations: (1) Chronic oral administration of 3-hydroxy-3-methylgiutaryl coenzyme A reductase inhibitors (statins) for reducing dyslipidemia and thereby cardiovascular morbidity and mortality, and (2) Chronic oral anticoagulation therapy with warfarin for dysrhythmias, prosthetic heart valves, congestive heart failure, and thromboembolism. These situations reflect high prevalence, considerable long-term risk, well defined and established therapies, demonstrable benefit exceeding risk from treatment, but disappointing overall impact in real world settings. Improving adherence for these situations should translate into better clinical outcomes and provide lessons useful for other conditions requiring long-term treatment with oral medications without prompts from symptoms. The project is a randomized controlled trial that (a) applies adherence-enhancing interventions at the levels of patient, physician, and medical care system for the two clinical situations; (b) demonstrates that improved levels of medication adherence occur in the INTERVENTION compared to the USUAL CARE groups; (c) evaluates the potential for dissemination by replicating into communitybased practices the successful interventions from academic clinic settings; and (d) assesses the cost-effectiveness of the interventions compared to usual care in both academic and community practice environments. The primary hypothesis is that the integrated interventions will achieve significantly higher levels of days with correct dosages for these two treatment conditions compared to usual care. The interventions reflect both social cognitive and self-determination theory as well as continuous quality improvement strategies using clinical process guidelines. Patients' achievements by levels of adherence and clinical control provide a strategic matrix for feedback that guides actions by the prescribing physician and the project educator. Electronic medication monitoring allows dynamic and comprehensive assessment of medication adherence by day as well as by longer interval corresponding to times of clinical visits and evaluation. Feedback from such monitoring for both patient and physician as well as physicians' adherence to practice guidelines provides keys to improving overall adherence and outcomes. 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
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Timing: Fiscal Year 2001; 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 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
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Project Title: IMPROVING SAFETY OF ANTICOAGULATION IN THE NURSING HOME Principal Investigator & Institution: Gurwitz, Jerry H.; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2001; Project Start 24-SEP-2001; Project End 31-AUG-2006 Summary: (PROVIDED BY APPLICANT) The premise underlying the proposed study is that deficiencies in the care of warfarin-treated residents in the nursing home setting place them at substantial risk for iatrogenic injury; these problems are related as much or more to problems in the system of providing this care as to deficits in the knowledge base of health care providers. We propose a study with the following objectives: 1. To evaluate the quality of anticoagulation management in the nursing home setting utilizing two principal quality measures: a) the proportion of time that nursing home residents receiving warfarin have their international normalized ratios (INRs) within the target therapeutic range; and b) the time until the next INR measurement when an out-of-target range INR value occurs. 2. To determine the rates of bleeding complications and potential adverse warfarin-related events (PAWEs) among warfarintreated residents of nursing homes. PAWEs are defined as incidents that have the potential to cause serious, life-threatening, or fatal bleeding, but in which bleeding does not occur. For the purpose of this study, a PAWE is defined as an INR level above 4.5.) 3. To assess the underlying causes and systems failures that lead to preventable warfarin-related bleeding events and PAWEs in nursing homes. 4. To appraise the process of anticoagulation management by means of total quality improvement techniques in each participating nursing home. 5. To lay the groundwork for a randomized trial, with randomization at the level of the nursing home, to evaluate the efficacy of coordinated anticoagulation care by a centralized, dedicated anticoagulation management service versus nursing home specific process improvements identified through total quality improvement methods. We propose to perform this study in 26 community nursing homes in Connecticut. This study will represent the efforts of a group of investigators and entities with the academic and technical capabilities to develop a best practices model to improve patient safety relating to anticoagulation therapy in the nursing home setting. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: IMPROVING THE USE OF ANTICOAGULANT THERAPY IN THE AGED Principal Investigator & Institution: Beyth, Rebecca J.; Assistant Professor of Medicine; Medicine; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2001; Project Start 01-SEP-1997; Project End 31-AUG-2002 Summary: Anticoagulant therapy is effective in the prevention of many thromboembolic disorders, such as stroke, myocardial infarction, and venous thrombembolism. In addition to being the most rapidly growing segment of our population, older patients are also the most likely to have these common indications for anticoagulant therapy. Although anticoagulant therapy has proven benefit in these conditions, it also has an adverse effect--bleeding. Concerns about this adverse effect of anticoagulant therapy may make clinicians less willing to prescribe anticoagulant therapy to older patients who might benefit most from treatment. The main goal of this proposal is to improve the use of anticoagulant therapy in older patients; it will also serve as a model for the investigation of other drug-induced illnesses in older patients Past studies and my own preliminary work indicate that warfarin-related bleeding may be more common in older
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patients. Which older patients are at greatest risk, and why they are more likely to bleed, is not known. This may lead physicians to erroneously under- or over-estimate the risk of warfarin-related bleeding in older patients, resulting in the withholding of therapy to some older patients whose benefit may outweigh their risk. Additionally, the attitudes and beliefs of physicians and patients about the risks of warfarin-related bleeding may affect the decision to initiate therapy. Clarification of these issues will lead to improvement in the appropriate use of warfarin therapy in older patients. I have designed an incremental research plan with three specific aims. Aims 1 and 2 will address critical unresolved issues involving the safety of anticoagulant therapy in older patients. Aim 3 will extend my research into a new area central to improving the use of anticoagulant therapy in older patients with atrial fibrillation--i.e., patient and physician attitudes concerning the risks and benefits of anticoagulant therapy, and the relationship of their attitudes to the appropriate use of anticoagulant therapy. This research proposal will build directly on my training and current work, while taking advantage of the research environment provided by my sponsors and others at Case Western Reserve University. It will also provide me with the scientific methods and clinical strategies to investigate other drug therapies in older patients, as well as to develop preventive strategies that will lead to improvements in the health care of older persons. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INFORMATICS TOOLS TO REDUCE WARFARIN ERRORS Principal Investigator & Institution: White, Richard H.; Associate Professor; Internal Medicine; University of California Davis Sponsored Programs, 118 Everson Hall Davis, Ca 95616 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 29-SEP-2004 Summary: Warfarin is currently prescribed to over 2 million Americans. It is perhaps the most hazardous drug commonly prescribed today. Dosing errors causing excessively high or low anticoagulant effects are common, particularly during the first month of treatment. Sources of correctable dosing errors have been identified and include poor dosing judgement, failure to recognize well-described drug interactions, and failure to communicate important dosing information during the transition between hospital and outpatient follow-up. The overall objective of this proposal is to advance patient safety by creating clinical informatics tools specifically designed to reduce the incidence of serious warfarin dosing errors in hospitalized patients being starting on warfarin for the first time. Our specific aims are to : 1) modify and enhance for easy use on a pocket PC computer a Bayesian forecasting program that predicts warfarin dose requirements, and couple this with a specially written program that identifies important drug interactions; 2) create for outpatient providers an Anticoagulation Discharge Summary Report that contains the important information necessary to make proper warfarin dosing after hospital discharge; and 3) conduct a large multi-centered clinical trial evaluating the effectiveness of their combined use in reducing warfarin dosing. The primary outcome will be incidence of an excessively high anticoagulant. However, in order to determine the extent to which use of these informatics tools leads to a more sustained impact after hospital discharge, we will quantify quantifying the incidence of thromboembolic or bleeding complications for 4 weeks after discharge. We will also evaluate the feasibility of using these informatics tools in routine hospital practice. After documenting the effectiveness of these informatics tools, they will be made open source and widely available for use by the public by placing them on a variety of web sites for easy downloading. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Warfarin
Project Title: MATRIX GLA PROTEIN AND ARTERY CALCIFICATION Principal Investigator & Institution: Price, Paul A.; Professor; Biology; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 92093 Timing: Fiscal Year 2001; Project Start 01-JUL-1998; Project End 30-JUN-2003 Summary: (Adapted from Investigator's Abstract): The objectives of this investigation are to define the contribution of warfarin treatment and of dietary vitamin K deficiency to the arterial calcification process in humans and in a rat model of the disease. The Principal Investigator will assess the molecular mechanism by which matrix Gla proteins, which are vitamin K dependent, can inhibit the arterial calcification process. The applicant will identify those risk factors which act synergistically with warfarin to accelerate arterial calcification in a rat model. He will establish the extent to which arterial calcification is arrested or reversed. Within the context of this specific aim, he will investigate the effect of dietary deficiency on the carboxylation of the Gla protein and the calcification in arteries in the rat. Dr. Price will also determine the effect of warfarin on the calcification of the intima in animal models of atherosclerosis and investigate the ability of the Gla protein infusion the arterial calcification that is induced by warfarin. The second aim, is designed to investigate the relationship between defective carboxylation of serum Gla protein and arterial calcification using isoelectric focusing and terminal protein sequencing; mineral binding activity will be done to measure carboxylation status. He will also look at the structure and functional associations of Gla protein and calcification sites in the human artery. The principal investigator will also investigate the mechanism by which the Gla proteins inhibit the calcification of elastin in the human aortic media when elastin is added to solutions that contain physiological concentrations of calcium and phosphate. He will also determine the role of Gla protein as an inhibitor of the growth of crystallites isolated by the human aortic media. These experiments are being done to establish the importance of vitamin K deficiency and of warfarin treatment as risk factors for the calcification of human arteries. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MECHANISMS INTERACTIONS
OF
ATYPICAL
DRUG
KINETICS
AND
Principal Investigator & Institution: Tracy, Timothy S.; Basic Pharmaceutical Sciences; West Virginia University P. O. Box 6845 Morgantown, Wv 265066845 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 30-JUN-2004 Summary: (Adapted from the Applicant's Abstract): Toxicological consequences may occur when drug interactions involve drugs with narrow therapeutic indices such as the cytocbrome P450 2C9 (CYP2C9) substrates warfarin and phenytoin. To minimize risk to humans, accurate predictions of in vivo drug metabolism, pharmacokinetics and drug interactions from in vitro data are needed. Recently, careful examination of drug metabolism kinetic data has demonstrated that atypical kinetics of cytochrome P450 mediated reactions may occur with greater frequency than previously believed. Atypical kinetic profiles such as autoactivation, activation and substrate inhibition have been observed for several P450 isoforms including CYP2C9. These atypical kinetic processes may be either homotropic (involving only one substrate) or heterotropic (involving a substrate and another effector/substrate). Since these kinetic patterns are observed in vitro and investigators use these in vitro data to predict in vivo pharmacokinetics, it is imperative that the mechanisms for these interactions be studied to form a better foundation for in vitro-in vivo predictions of human drug metabolism and drug
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interactions. We hypothesize that critical amino acid changes in the CYP2C9 enzyme can alter the degree of cooperativity observed, that key molecule structural characteristics are required for heterotropic cooperativity, that these cooperativity interactions can be modeled and cooperativity can be observed in vivo. Using expressed CYP2C9 allelic variants and site-directed mutagenesis, metabolism of CYP2C9 substrates, which exhibit various kinetic profiles, and their interactions with a known effector (and a series of structural analogs) will be studied and modeled. Additionally, in vivo studies of a CYP2C9 substrate and a known (in vitro) effector will be conducted. Taken together, these results will improve CYP2C9 in vitro-in vivo predictive capabilities. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MEDICATION ERRORS LEADING TO HOSPITALIZATION OF THE AGED Principal Investigator & Institution: Metlay, Joshua P.; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 07-SEP-2001; Project End 31-AUG-2006 Summary: (PROVIDED BY APPLICANT) Medication errors leading to adverse events are a major cause of preventable hospitalizations, particularly among the elderly. Medication errors that result in dose-related adverse events can occur anywhere along the medication use process. The specific causes of and solutions for medication errors are likely to differ across drugs with different properties. Thus, investigations of errors must focus on specific drugs, particularly those with a narrow therapeutic index, such as warfarin, phenytoin, and digoxin. Error prevention strategies might include programs that improve therapeutic drug dosing and monitoring (phenytoin), improve patient drug adherence (warfarin), or reduce physician gaps in knowledge about the risks and benefits of drugs (digoxin). However, the precise design of interventions requires information on the underlying causes of these errors for both new and chronic users of these specific agents. Moreover, such interventions will only be feasible if they can be targeted to high-risk groups of patients for whom the absolute risk of adverse events due to medication errors is sufficiently high to justify these interventions. The primary aim of this project is to identify predisposing factors for hospitalizations due to errors in medication use among a large, representative cohort of community-dwelling elderly patients initiated or maintained on warfarin, phenytoin, and digoxin. The primary study hypothesis is that uncoordinated medical and pharmaceutical care, inadequate delivery of new medication instructions, visual and cognitive impairment, and psychosocial barriers (depression, coping, and support) are predisposing factors for medication errors resulting in hospitalization. The secondary aims of this study are (1) to develop a prediction rule to identify elderly outpatients at high risk for hospitalization due to errors in use of these drugs, and (2) to estimate the costs associated with hospitalization due to these errors. The hypotheses for these aims are: (1) patient factors can be used to accurately predict groups at high risk for these hospitalizations, and (2) the costs of these errors outweigh the costs of potential targeted interventions. The proposed study is a prospective cohort study enrolling members of the Pennsylvania Pharmaceutical Assistance Contract for the Elderly (PACE). Subjects will be sampled across the State to ensure geographic diversity in the study sample. At the time of enrollment in the cohort, subjects will undergo a detailed baseline interview to identify key psychosocial, behavioral, and clinical predictors. Outcomes will be identified over a two-year follow-up period by regular phone contact with cohort members using a screening instrument to identify hospitalizations. Medical records will be reviewed, and clinical findings, along with admission drug or anticoagulation levels,
24
Warfarin
will be used to identify hospitalizations that are likely due to medication errors. Analyses will focus on the identification of risk factors and development of a prediction rule to identify subjects at high risk of hospitalization due to medication errors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MEMBRANE PROTEINS IN BLOOD COAGULATION Principal Investigator & Institution: Furie, Barbara C.; Director; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215 Timing: Fiscal Year 2001; Project Start 01-APR-1989; Project End 31-AUG-2004 Summary: This program project application represents a renewal of a coordinated multi-laboratory investigation of the synthesis of g-carboxyglutamic acid in the membrane binding Gla domain of the vitamin K-dependent blood clotting proteins and the mechanism by which blood clotting proteins assemble on membrane surfaces. The program has involved collaborations among five laboratories, with most of the activities focused at the Center for Hemostasis and Thrombosis Research at the Beth Israel Deaconess Medical Center/Harvard Medical School. Dr. Barbara C. Furlie is the Director of the Program and Dr. Bruce Furie is the co-Director. The first project (Structure-Function of the g-glutamyl carboxylase; Dr. Barbara C. Furie and Dr. Christopher Walsh) will explore the structure and function of the carboxylase. With suitable, homogeneous quantities of the vitamin K-dependent carboxylase available for biochemical analysis, the proposed project will elucidate important aspects of carboxylase mechanism, carboxylase structure-function relationships and in vivo tissuespecific functions of carboxylase using a carboxylase null mouse model. Embryonic Synthesis and Function of g-Carboxyglutamate; Dr. David Roth defines the mechanisms underlying the regulation of Gla synthesis in developing and differentiated tissues, and provide insights into the pathogenesis of the warfarin embryopathy in studies of the transcriptional control of the carboxylase gene. The next project (Factor IX Complexes on Membrane Surfaces; Dr. Bruce Furie) will study the structure of Factor IX- membrane interaction and the structure of the Factor IXa-Factor VIIIa complex on membrane surfaces. The last project (Phospholipid Binding Structures of Factor VIII; Dr. Gary Gilber) will study the mechanism by which Factor VIII binds to membranes and the role of a peptide based upon the structure of Factor VIII to accelerate Factor X activation by Factor IXa. The program includes three Core Units: an administrative core; an analytical core for synthesis of peptides and protein sequencing; a cell culture and animal core. The motivation for this program is to maintain an experienced interdisciplinary group to approach significant, challenging problems that are beyond the scope of a single investigator. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NATIONAL TRENDS IN OUTPATIENT QUALITY INDICATORS Principal Investigator & Institution: Stafford, Randall S.; Assistant Professor; Medicine; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2005 Summary: Despite the increasing attention on health care quality improvement in the U.S., the national quality of outpatient health care services has not been assessed. Particularly lacking are rigorous evaluations of trends in the quality of outpatient care for racial and ethnic minorities. This application will address this issue using data from the 1992-2001 National Ambulatory Medical Care Surveys (NAMCS) and National Hospital Ambulatory Medical Care Surveys (NHAMCS). Its aims are to: 1) construct a
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25
set of outpatient quality indicators, 2) assess quality of care at the national level using the selected indicators, 3) evaluate time trends in these indicators, and 4) determine patient, physician and organizational predictors of quality of care, with a particular focus on racial/ethnic minorities. A set of 27 proposed quality indicators will provide a quantitative assessment of quality and will cover: 1) recommended medications (e.g., warfarin in atrial fibrillation), 2) antibiotic use (e.g., antibiotics in viral respiratory infections), 3) physician counseling/disease management (e.g., dietary counseling in diabetes), 4) diagnostic testing (e.g., screening urinalysis tests), and 5) medication errors (e.g., risky drug-drug interactions). 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; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215 Timing: Fiscal Year 2001; Project Start 01-SEP-2000; Project End 30-JUN-2002 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 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
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Project Title: PHARMACOGENETIC OPTIMIZATION OF ANTICOAGULATION THERAPY Principal Investigator & Institution: Limdi, Nita A.; Neurology; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 28-FEB-2008
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Warfarin
Summary: (provided by applicant): The use of warfarin, although widely accepted for ischemic stroke prevention, is hindered by factors influencing its efficacy and toxicity. Warfarin is metabolized by Cytochrome P4502C9 (CYP2C9). There are several CYP2C9 alleles, which encode for enzymes with different catalytic activity. These have been documented for CYP2C9*1, CYP2C9*2, and CYP2C9*3. Recently three additional alleles have been identified: CYP2C9*4, CYP2C9*5, and CYP2C9*6 the latter two in African Americans. The primary hypothesis of the study is that the CYP2C9 genotype influences the dose of warfarin required to maintain anticoagulation and the variability in INR control. The secondary hypothesis is that patients carrying variant alleles are at a higher risk for hemorrhagic complications. Conversely the patients who carry the normal allele may be at a higher risk of recurrent thromboembolic events. These hypotheses will be tested in a cohort of 500 stroke patients, including African-Americans. Patients will be identified prior to initiation of therapy and followed for 2 years. The study will establish the association between genotype and warfarin dose and the association between genotype and the frequency of INRs outside target range and the risk of associated complications both hemorrhagic and thromboembolic. Multivariate analysis will evaluate the association of CYP2C9 genotype-warfarin dose and genotype-INRs outside target range and associated complications both hemorrhagic and thromboembolic. Confounding variables - drug interactions, co-morbid conditions, and compliance will be statistically controlled. The advantage of defining CYP2C9 genotype will increase precision of warfarin dosing, achieve therapeutic anticoagulation earlier, minimize variability in INR, decrease the risk of thromboembolic/hemorrhagic events and reduce health care costs. My career goals are to investigate the influence of genetics on drug response. With the award of the K23 grant, structured training, guidance of mentors, environment and institutional support provided by the University, I will develop the skills necessary for a productive career in pharmacogenetics research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PHARMACOGENETICS AND ANTITHROMBOTIC THERAPY Principal Investigator & Institution: Gage, Brian F.; Barnes-Jewish Hospital Ms 90-94-212 St. Louis, Mo 63110 Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 28-FEB-2004 Summary: (provided by applicant): Our long-term goal is to prevent death and disability from thrombotic events. Recently, we have been studying how to manage and dose Warfarin therapy and how to prevent stroke in patients who have atrial fibrillation. A major problem with prescribing Warfarin therapy is that its narrow therapeutic index and "idiosyncratic" response conspire to make its initiation protracted and dangerous. The proposed study focuses on how genetic and clinical factors can be used to predict this response. The primary objective of this 2-year proposal is to construct, validate, and use a warfarin-dosing algorithm for initiation of therapy. The secondary objective is to validate the paradigm that knowledge of pharmacogenetics can decrease the toxicity of commonly prescribed drugs. The study has 4 aims: 1. To construct a genetic-based, warfarin-dosing algorithm that will guide warfarin induction. To develop the algorithm, we will use clinical data and genetic specimens that we have obtained from 298 patients taking chronic warfarin therapy. We propose to complete our genotyping of these specimens for single nucieotide polymorphisms (SNPs) of the cytochrome P450 2C9 gene. We will test Hypothesis 1: The warfarin dosing algorithm will explain at least 30% of the variance in the therapeutic dose. 2. To validate the genetic-based, warfarin-dosing algorithm in an independent sample of 250 patients. We will test Hypothesis 2: The dosing algorithm will explain at least 30% of the variance in
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27
the therapeutic warfarin dose in the validation sample. 3. To use genetic-based warfarin dosing in 50 patients beginning warfarin therapy. We will use the genetic- based algorithm to initiate warfarin therapy in a pilot study of 50 patients. We will test Hypothesis 3: As compared to historic controls whose warfarin is initiated empirically, participants who use genetic-based warfarin dosing will be prescribed their therapeutic dose sooner. 4. To correlate genetic and clinical factors with the plasma level of free warfarin. Using high performance liquid chromatography, we will measure the levels of the 2 enantiomers of warfarin and test Hypothesis 4: Clearance of S-warfarin will be significantly decreased in the presence of 2C9 SNPs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PHARMACOGENETICS IN SURGICAL CRITICAL CARE Principal Investigator & Institution: Freeman, Bradley D.; Assistant Professor; Surgery; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-AUG-2005 Summary: (Adapted from the applicant's abstract) The applicant proposes that using pharmacogenetics (i.e., drug prescription based on a patient's genetic background) may dramatically enhance the efficacy of many therapies commonly used in critically ill patients. The PI for this career development award is a trauma/critical care surgeon whose long term research career goal is the application of pharmacogenetic techniques to surgical critical care. As an immediate goal, the PI seeks to develop expertise in molecular genetic techniques essential to this type of translational research. The research proposal, which examines warfarin pharmacogenetics, will provide the framework for achieving the immediate goal through a period of instruction, supervision, and investigation based in a clinical molecular diagnostics laboratory. Like many drugs used in surgical critical care, warfarin has a narrow therapeutic index, an unpredictable doseresponse, and untoward interactions with many medications. Despite frequent monitoring, potentially lethal toxicities are common. Current empiric methods of warfarin dosing are inaccurate. Warfarin is metabolized by two distinct subfamilies of the cytochrome P450 complex: CYP2A6 and CYP2C9. Common polymorphisms of these enzymes result in impaired warfarin metabolism. Interindividual variability in warfarin dosing may be attributable to these polymorphisms. The hypothesis is that warfarin dosing based on CYP2C9 and CYP2A6 genotyping will be more accurate and effective than current methods. To address this hypothesis, the applicant will accomplish two Specific Aims. He will (1) determine the frequency of CYP2C9 and CYP2A6 polymorphisms in an ethnically defined population of patients receiving warfarin; and (2) establish the relationship between CYP2C9 and CYP2A6 genotypes and warfarin dose and develop a genetically-based approach to warfarin dosing. The environment for this project is Washington University School of Medicine, an institution with access to a large clinical volume and established expertise in genomic research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PHARMACOGENOMICS OF ARRHYTHMIA THERAPY Principal Investigator & Institution: Roden, Dan M.; Professor; Medicine; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2001; Project Start 24-SEP-2001; Project End 31-JUL-2005 Summary: Sudden death due to ventricular fibrillation kills 250,000-500,000 Americans each year and up to 5,000.000 American have a history of atrial fibrillation, which is associated with stroke, heart failure, and increase mortality. There is substantial inter-
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Warfarin
individual variability in response ti ion channel blocker, B-blocker, and warfarin, drugs widely used in the therapy of arrhythmias; some patients display beneficial effects, while others exhibit lack of efficacy or even life- threatening adverse effects. The hypothesis to be tested here is that allelic variants in candidate genes- implicated by an emerging understanding of molecular physiology and pharmacology-contribute to such variable drug responses. Work in our laboratories and elsewhere has identified allelic variants, and their functional consequences, in candidate genes, including drug metabolizing enzymes, ion channel proteins, and components of intracellular signaling systems. We have 4 Specific Aims: (1) to expand polymorphism discovery, focusing on new candidate genes; to determine frequencies of common polymorphisms in defined ethnic groups; and to ealuate variant protein function in vito; (2) to assess the role of allelic variants in modulating atrial and ventricular fibrillation and their response to drugs; (3) to determine the value of pre-prescription genotyping for QT prolonging antiarrhythmics and for warfarin; and (4) to use acute challenge with ibutilide and atenolol in sib-pairs to identify familial component(s) in drug responses (QT and heart rate change), and to determine the role of candidate and gene-gene interactions in modulating those responses. The studies will be supported by expertise in clinical pharmacology, clinical and basic electrophysiology, genetic epidemiology, bioinformatics, and polymorphism discovery and allele typing. This research will rigorously test the concept that advances in genetic science and molecular pharmacology can be combined to improve drug therapy. The outcomes will be not only improved drug therapy of arrhythmias, but also further development of appropriate methods to exploit genomic science to enhance drug therapy in general. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PREVENT: THROMBOEMBOLISM
PREVENTION
OF
RECURRENT
VENOUS
Principal Investigator & Institution: Cushman, Mary; University of Vermont & St Agric College 340 Waterman Building Burlington, Vt 05405 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PREVENT: THROMBOEMBOLISM
PREVENTION
OF
RECURRENT
VENOUS
Principal Investigator & Institution: Key, Nigel S.; Associate Professor; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2001 Summary: Standard of care for patients with deep venous thrombosis (blood clot in the leg or arm) and the complication of pulmonary embolus (blood clot in the lung) typically includes anti coagulation (blood thinning) medication for a 3 to 6 month period with full dosewarfarin (coumadin). Patients following this regimen experience high rates of recurrent thrombosis, and re-hospitalization in the years immediately following cessation of anticoagulation. This is true for patients at average risk of disease recurrence, and for patients at increased risk due to the presence of inherited defects of anticoagulation such as the factor V Leiden mutation. No clinical regimen currently available has proven to have sufficient benefit to support long term prophylaxis. Simply put, using current standards of anticoagulation with warfarin in the long term, the undoubted benefit in preventing clots is often negated by the excess risk of bleeding. In
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contrast, while targeted low dose warfarin is safe for long term therapy with respect to bleeding risk, the effectiveness of this approach is untested. The research question is: Will long term low dose warfarin effectively prevent venous thromboembolic disease? The Prevention of Recurrent Venous Thromboembolism (PREVENT) trial will evaluate the effectiveness of long term therapy with low dose warfarin in the secondary prevention of venous thromboembolism (VTE). Patients with a history of documented unexplained venous thrombosis who have completed a standard course of anticoagulation therapy will be enrolled in a randomized, double-blind, placebocontrolled trial comparing usual care plus low-dose warfarin to usual care plus placebo for a period of up to 4years. Trial end-points will include recurrent VTE, major bleeding episodes, and all deaths in the total patient population and separately in those patients with factor V Leiden. The potential clinical impact of the PREVENT trial is broad since a positive finding would strongly support chronic low dose anticoagulation among patients with venous thrmobosis who are at risk for recurrence following cessation of standard outpatient anticoagulation. This intervention trial will be conducted among 800 men and women ages 40 and over who have had a prior venous thrombosis, and thus may be at risk for future recurrence. With 40 centers nationwide participating in this trial we estimate approximately 30 patients will be recruited from FairviewUniversity Medical Center (F-UMC). Participation will involve 3-4 years of study treatment and follow-up. The General Clinical Research Center (GCRC) will provide physical space to facilitate all patient visits at each time point. GCRC nursing and ancillary staff will be asked to obtain applicable measurements, vital signs, perform venipuncture, necessary centrifuging of blood speciments, and point of care unblinded Coag-u-check testing for INR (see physician orders). In addition, nursing staff will be asked to document current medications at all time points. An in-service will be provided to nursing staff who will need to perform Coag-u-check INR. Although 29 visits are expected per patient there may be accasional unscheduled visits. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PREVENTION OF RECURRENT THROMBOEMBOLISM Principal Investigator & Institution: Kerins, David M.; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2001 Summary: The primary aim of this trial is to assess the net clinical benefit of 3-4 years of low-dose warfarin in the secondary prevention of idiopathic venous thromboembolism. The trial has been designed to test a safe and efficacious warfarin regimen which, after initial titration, will require infrequent outpatient blood or laboratory monitoring and thus will appeal to clinicians and patients currently reluctant to use long-term warfarin for secondary prevention. The trial will also evaluate participants with and without factor V Leiden, a recently described common inherited defect of anticoagulation which results in activated protein C resistance and increased risk of recurrent thrombosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PREVENTION OF RECURRENT VENOUS THROMBOEMBOLISM (PREVENT) Principal Investigator & Institution: Hambleton, Julie; Associate Clinical Professor of Medicine; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2001
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Warfarin
Summary: This is a double-blind, placebo-controlled trial of low-dose warfarin in the secondary prevention of venous thromboembolism. The primary aim of this trial is to assess the nect clinical benefit of three-to-four years of low dose warfarin, with a target INR of 1.5-2.0, in the secondary prevention of idiopathic venous thromboembolism. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SECONDARY PREVENTION TRIAL OF VENOUS THROMBOSIS Principal Investigator & Institution: Ridker, Paul M.; Associate Professor; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2001; Project Start 11-SEP-1998; Project End 31-AUG-2003 Summary: The aim of this proposal is to assess the efficacy of prolonged treatment with low dose warfarin in the secondary prevention of venous thromboembolism (VTE) among patients with and without factor V Leiden mutation, a common inherited defect of hemostasis associated with increased risk of recurrent thrombus formation. The investigators propose to conduct a randomized, double-blind, placebo-controlled, multicenter trial among 800 men and women age 40 or greater with a documented idiopathic venous thrombosis who have completed a standard course of anticoagulation therapy within the last two years. Enrollment will be targeted to ensure at least 300 patients with factor V Leiden are randomized. Patients will be randomized to usual care plus placebo or to usual care plus a three to four year regimen of low-dose warfarin (intended INR 1.5-2.0). After an initial titration period, double-blind INR assessment and dose adjustment will be performed for all patients every two months, with a weekly followup whenever a blinded dose adjustment greater than 1 mg is made, and on an as needed basis consistent with best clinical judgment. Trial endpoints will include recurrent VTE, major bleeding episodes, and all cause mortality in the total patient population and separately in those patients who have factor V Leiden. Both qualifying events and reported endpoints will be confirmed by detailed medical record review using standardized diagnostic criteria based upon venographic and doppler ultrasound data, ventilation- perfusion scans, and pulmonary angiography. The trial has sufficient power to discern whether prolonged anticoagulation with low dose warfarin will reduce rates of recurrent disease with low bleeding risks both for all patients enrolled and for the subgroup of those who carry factor V Leiden mutation. The potential clinical impact of this trial is broad since a positive finding would strongly support chronic anticoagulation among the 300,000 US patients hospitalized each year with venous thrombosis who are at risk for recurrent disease following cessation of standard outpatient anticoagulation and for whom there is no regimen currently proven to have an acceptable risk to benefit ratio to support long term prophylaxis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SECONDARY PREVENTION TRIAL OF VENOUS THROMBOSISDCC Principal Investigator & Institution: Glynn, Robert J.; Associate Professor; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2001; Project Start 11-SEP-1998; Project End 31-AUG-2003 Summary: Venous thromboembolic disease (VTE) is associated with more than 300,000 hospitalizations and results in thousands of deaths annually. Despite the magnitude of the problem, optimal management of patients experiencing first deep vein thrombosis is unclear. Current treatment includes short-term full dose oral antithrombotic therapy with warfarin. Unfortunately, this treatment is associated with a very high rate of
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recurrence once therapy is stopped. In addition, poor compliance secondary to frequent laboratory monitoring and bleeding complications limit this treatment regimen's overall effectiveness. Presently, there is no clinical regimen which has been proven to have an acceptable risk/benefit ratio to support long-term prophylaxis. This appears true for high risk patients (factor V Leiden mutation) as well as for the general population. The primary aim of this proposal is to assess the net benefit of 3 to 4 years of low-dose warfarin (1.5-2.0) in the secondary prevention of idiopathic venous thromboembolism. The proposal is designed to evaluate patients with and without factor V Leiden. The proposed trial is a randomized double-blind, placebo-controlled trial of 3 to 4 years of anticoagulant therapy with low-dose warfarin prevention of recurrent deep vein thrombosis. The study will enroll 800 patients. Enrollment is designed to ensure participation of 300 patients with factor V Leiden. Patients will be enrolled from 25 clinical sites. Men and women of 40 years with documented idiopathic VTE who have finished standard therapy will be randomized to usual care plus placebo or usual care plus a 3- year regimen of low-dose warfarin. Following titration, the protocol will require infrequent laboratory monitoring. Trial endpoints include recurrent venous thrombosis, major bleeding, and all cause mortality for the group as a whole or factor V Leiden mutation subgroup. Events will be assessed by yearly visits and bi-monthly questionnaires at the time of the INR monitoring. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STROKE OUTCOME AND NEUROIMAGING OF INTRACRANIAL STENOSIS Principal Investigator & Institution: Feldmann, Edward; Associat Professor; Rhode Island Hospital (Providence, Ri) Providence, Ri 02903 Timing: Fiscal Year 2001; Project Start 15-SEP-1999; Project End 30-JUN-2004 Summary: Intracranial atherosclerosis is responsible for 50,000 ischemic strokes each year in the USA. Noninvasive testing such as transcranial Doppler ultrasound (TCD) and magnetic resonance angiography (MRA) to identify intracranial atherosclerosis is in widespread use but has not been rigorously validated against the gold standard, catheter angiography. The recently NIH-funded WASID trial (Warfarin Aspirin Symptomatic Intracranial Disease) will compare warfarin with aspirin for stroke prevention in patients with intracranial atherosclerosis. WASID requires performance of angiography along with TCD and MRA, providing an opportunity to critically evaluate these nonivasive tests. Main Objective. The purpose of SONIA is to validate the noninvasive diagnosis of intracranial atherosclerosis. The primary aim of SONIA is to define velocity values on TCD and anatomic abnormalities on MRA that identify severe (50-99 percent) intracranial stenosis or large, proximal arteries seen on catheter angiography. SONIA will define the criteria, or cutpoints, for an abnormal TCD or MRA and show that they perform with a reliable positive predictive value (PPV). Study Design. SONIA will be conducted in collaboration with WASID. Study-wide cutpoints defining positive TCD and MRA have been developed and reviewed by the site investigators of WASID. Hard copy angiography, TCD and MRA generated in WASID will be centrally read in SONIA. The performance of TCD and MRA will be monitored and analyzed in SONIA to demonstrate cutpoints that achieve a PPV of 80 percent for the identification of severe intracranial stenosis on angiography. Conclusions. Central readings will be used to validate the cutpoints that function with a PPV of 80 percent and to develop measures of negative predictive value (NPV), inter- and intra-observer variability. Sensitivity and specificity will be determined after adjustment for verification bias and employed in receiver-operator characteristic analyses. SONIA will
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Warfarin
use these techniques to develop TCD or MRA cutpoints that minimize the clinical consequences of test errors that occur in the noninvasive evaluation of patients with suspected intracranial atherosclerosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STRUCTURE FUNCTION RELATIONSHIPS OF FACTOR IX Principal Investigator & Institution: Roberts, Harold R.; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2001 Summary: The purpose of this project is to understand the function of the gammacarboxyglutamic (Gla) domain of vitamin K-dependent coagulation factor IX. Understanding the Gla domain, the location both of factor IX binding to collagen IV and platelets and also of carboxylation, can advance knowledge about hemostasis. A better understanding of the molecular basis of factor IX's activity could have clinical applications in the treatment of thrombosis. First we will attempt to determine the physiological relevance of factor IX's binding to collagen IV by examining the phenotype of a mouse with a mutant factor IX unable to bind collagen IV. Second, to determine if collagen IV is intracellular or is actually found on the surface of endothelial cells lining the lumen of both arteries and veins where it is (uniquely among vitamin Kdependent clotting factors) co-localized with factor IX, we will utilize monoclonal antibodies together with colloidal gold and electron microscopy. Third, to identify residues of collagen IV to which factor IX binds, we will utilize chemical cross-linking techniques. Fourth, since a specific region of the factor IX Gla domain binds to platelets, we propose to use the photochemical cross-linker benzoyl- phenylanine to identify and purify the receptor. Fifth, we will continue our studies on substrates for the carboxylase by examining several new constructs for their activity in an in-vitro carboxylase assay and determining if a specific sequence is required for the carboxylation of vitamin Kdependent protein in-vivo. A plausible mechanism to explain the defects in conditional hemophilia B patients identified during the tenure of our current project will be very important to understanding how these pro-peptide mutations are leading to hemophilia B in the presence of warfarin. Moreover, knowledge of the mechanism of carboxylation and the importance of each residue of the pro-peptide in carboxylation may allow the development of anticoagulents specific for a particular vitamin K- dependent coagulation factor. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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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 2001; Project Start 01-APR-1997; Project End 14-DEC-2002 Summary: (Adapted from investigator's abstract): One of the key pieces missing in understanding the regulation of hemostasis is the mechanism by which the vitamin Kdependent (VKD) clotting factors are carboxylated. Carboxylation is a post-translational modification that proteins like prothrombin, factor IX and factor VII require for activity. It involves the conversion of clusters of glutamyl residues to gamma carboxyglutamyl residues in a reaction that requires vitamin K hydroquinone and is inhibited by the anticoagulant Warfarin, a vitamin K antagonist. Carboxylase activity resides in an integral membrane protein present in most tissues. Carboxylated VKD proteins have
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also been isolated from bone and smooth muscle. Whether there are multiple carboxylases for the different VKD proteins or only a single enzyme remains an open question. The carboxylation of VKD proteins is poorly understood. Most of the studies have been performed using crude microsomal preparations on small synthetic peptide analogs based on sequences derived from the VKD proteins. The carboxylase cDNA has been isolated, but the protein encoded by it does not share homology with other known proteins, and the cDNA provides little suggestive information about carboxylase structure or function. Dr. Berkner's lab has developed a novel, model system for analyzing the intracellular interaction of the carboxylase with individual recombinant VKD proteins in mammalian cells. This system allows for isolation of the carboxylaseVKD protein enzyme-substrate complex for in vitro analysis. Dr. Berkner has also constructed cell lines that over-express the carboxylase and can now isolate large amounts of pure, active human carboxylase. Long-term goals are to understand the mechanism of carboxylation and the role that the carboxylase plays in multiple biological systems. Specific aims for this grant period are to: 1) analyze the domain organization of the carboxylase; 2) analyze the mechanism of VKD protein carboxylation by identifying the limiting step in the secretion of carboxylated proteins; 3) test whether there are multiple carboxylases or if one carboxylase modifies all VKD proteins. Data from these experiments will elucidate why the carboxylation of VKD proteins is limited in vivo even when the carboxylase is overexpressed and how the carboxylase carries out this unusual, and critical, reaction. These experiments will also provide methods for the future isolation of VKD proteins and information for the design of anticoagulants that specifically alter hemostasis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SUDDEN CARDIAC DEATH IN HEART FAILURE TRIAL OF AMIODARONE, OR ICD Principal Investigator & Institution: Halperin, Blair; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2001 Summary: The purpose of this study is to determine whether the likelihood of death in people with weak hearts can be lessened. There are two principal causes of death in people with decreased heart strength: progressive, profound heart muscle weakness and severe heart rhythm disorders (ventricular fibrillation). Ventricular fibrillation is a rapid disorganized beating of the lower heart chambers, (ventricles), causing death because the heart can no longer pump blood effectively. This study will examine whether ventricular fibrillation can be prevented. People with decreased heart strength can also die from progressive heart weakness. Entry into the study will not alter the standard care given to individuals for the treatment of a weak heart. Standard therapy includes the use of diuretics (water pills like furosemide and hydrochlorothiazide), afterload reducers (enalapril, lisinopril, captopril, hydralazine, nitrates, and related drugs) and/or, digitalis (digoxin). Standard therapy may also include blood thinners (aspirin and warfarin), beta-blockers (metoprolol, atenolol), and, in patients with severely weakened hearts, heart transplantation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: THE COAGCARE ANTICOAGULATION MANAGEMENT SYSTEM Principal Investigator & Institution: Allen, Lyle M.; Zycare, Inc. 3804 Sweeten Creek Rd Chapel Hill, Nc 27514
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Warfarin
Timing: Fiscal Year 2001; Project Start 01-MAR-2001; Project End 31-AUG-2001 Summary: The major goal of Phase I is to finish development of the CoagCare(TM) System, an Internet-enabled system for the automated management of oral anticoagulation therapy with warfarin. ZyCare, Inc. is developing detailed specifications for the system and is currently coding the software for the system. One U.S. patent has already been awarded for the CoagCare(TM) System and another is pending. CoagCare(TM) has two essential components for treatment delivery, the CoagCare(TM) Patient Module (CPM) and the CoagCare(TM) Caregiver Module (CCM) for use by healthcare professionals managing patients. Software for the CPM and CCM will run on a browser that can be accessed from a variety of platforms with an Internet connection. During Phase I, formal detailed specifications and software for the CPM and CCM coding will be completed. We will also develop a specification for special evaluation software for the CPM. This software, the CPM Professional Assessment System (CPM-PAS), will allow professionals who manage anticoagulation therapy to formally evaluate the interface, content, and decision-making performed by the CPM and assist software engineers in validating the core functions of the CPM during Phase II. The major milestones we plan to achieve before beginning Phase II are to complete the initial versions of the CPM, CCM and to develop the specification for the CPM-PAS for formal validation of the CoagCare(TM) system. PROPOSED COMMERCIAL APPLICATION: The CoagCare (TM) System described promises to revolutionize the management of warfarin therapy by automating patient self-management and physician supervision. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TRENDS IN AND OUTCOMES OF MEDICATION USE IN OLDER ADULTS Principal Investigator & Institution: Psaty, Bruce M.; Professor, Medicine and Epidemiology; Medicine; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2001; Project Start 01-SEP-1993; Project End 30-JUN-2005 Summary: This proposal, the 2nd revision of a competing continuation last reviewed in March 2000, is an ancillary study to the Cardiovascular Health Study (CHS), a cohort study of risk factors for coronary disease and stroke in 5888 older adults. This revision addresses questions such confounding and interpretation raised by the Study Section. In CHS, medical conditions are well characterized, and participants are followed closely for events. CHS clinic visits, where medication data had been collected, ended in 1999, and the NHLBI plans to provide full support only for events follow-up for an additional 5 years. This project provides support to 4 Field Centers to continue to collect medication data by telephone interview and to CHS scientists to continue analyses of these data. In a pilot study of 74 subjects, agreement between in-clinic and telephoneinterview medication inventories was excellent. The purpose is to assess use of cardiovascular medications and their associations with outcomes among older adults. To date, the project is associated with 26 publications and 7 presentations. The aims, which focus on the use of cardiovascular medications and their association with events, are consistent with PA99-097 entitled, "Diversity in Medication Use and Outcomes in Aging Populations." One innovative feature of this study is the age of the cohort. At baseline in 1989-90, the mean age of the CHS cohort was 72.8 years, and as of Oct 1999, the mean age of the survivors was 81.2 years: 2290 (55.9 percent) of the 4095 surviving CHS participants are 80 years of age or older. Over the last several decades, the results of randomized clinical trials and meta-analyses have helped to define optimal care for
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patients with cardiovascular disease or with risk factors for cardiovascular disease. Guidelines have been formulated for the care of patients with coronary disease or with risk factors such as elevated levels of cholesterol or blood pressure. But information about the implementation of guidelines or the effect of clinical trials on practice patterns is often lacking for older adults; and we also lack information about the efficacy and safety of most medications for older adults, especially the oldest old, who are the fastest growing segment of the US population. The aim of this project is to describe the use of various cardiovascular medications and their association with outcomes among older adults. The project has good to excellent power for a number of hypotheses, including: the use of ACE inhibitors and beta- blockers in subjects with heart failure or coronary disease and their association with total mortality; the use of warfarin in patients with atrial fibrillation and their association with stroke or death; the use of blood pressure and lipid lowering medications and their association with cardiovascular events and cognitive function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: VENOUS THROMBOEMBOLISM AMONG CALIFORNIA CANCER PATIENTS Principal Investigator & Institution: Chew, Helen K.; Internal Medicine; University of California Davis Sponsored Programs, 118 Everson Hall Davis, Ca 95616 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): Venous thromboembolism (VTE, includes both venous thrombosis and pulmonary embolism) is a frequent complication among patients with cancer. However, there is surprisingly little data regarding the incidence and time course of VTE and the risk of recurrent VTE among patients with a specific malignancy defined by histologic type and stage. In addition, it is not clear to what degree age, sex, ethnicity, stage, histologic type, and treatment predict the development of VTE. This information is important because there is preliminary data suggesting that use of anticoagulants, such as warfarin or low molecular weight heparin, may be beneficial in the primary prevention of VTE among cancer patients. The specific aims of this application are: 1) to define a cohort of patients diagnosed with one of the ten most frequent cancers in California and to identify hospital-reported cases of VTE in this cohort by linking the California Cancer Registry with the California Patient Discharge Data Set; 2) to determine and compare the incidence and time course of incident VTE after diagnosis of the most frequent cancers in California; 3) to determine demographic, treatment- and disease-related risk factors associated with developing VTE after diagnosis of the most frequent cancers in California; 4) to determine predictors of death within two years of diagnosis of each of the ten most frequent cancers in California; and 5) to determine the incidence of recurrent VTE and re-hospitalization for bleeding within a six-month period after diagnosis of incident VTE and to compare this to the incidence in age- and sex-matched patients with VTE who do not have cancer. The hypothesis are: 1) a cohort of cancer patients who develop VTE can be identified through the California Cancer Registry and the California Patient Discharge Data Set; 2) there is a significant variation in the incidence and time course of incident VTE among the ten most frequent cancer diagnoses, and among the different stages of each of these malignancies; 3) for each type of cancer, there is ethnic variation in the incidence of VTE, and factors such as age, stage, and therapy, will influence the observed rates of VTE in cancer patients; 4) for all malignancies, the development of VTE within 2 years of diagnosis is an independent predictor of death within 2 years of diagnosis; and 5) patients with cancer who develop VTE have a higher incidence of both recurrent VTE
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Warfarin
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 •
Project Title: VITAMIN K, METABOLISM AND FUNCTION Principal Investigator & Institution: Wallin, Reidar; Internal Medicine; Wake Forest University Health Sciences Winston-Salem, Nc 27157 Timing: Fiscal Year 2001; Project Start 01-APR-1998; Project End 30-SEP-2003 Summary: Understanding vitamin K-dependent proteins will require insight into their biosynthesis and regulation. Unique for these proteins is their vitamin K-dependent post-translational modification. The modification is carried out by the _-carboxylase, an integral protein of the ER membrane which uses the reduced form of vitamin K (vitamin KH2) as cofactor. The reduced cofactor is produced by the enzyme Vitamin K 3,4Epoxide reductase (VKOR) which is the target for the anticoagulant drug warfarin. Despite numerous attempts to purify VKOR, the molecular components that constitute the enzyme have not been identified. The applicants have been able to show that VKOR is an enzyme complex in the ER membrane and they propose that assembly of the complex is similar to assembly of the lipoxygenase complex on the nuclear envelope membrane. Both enzymes incorporates a member of the glutathione-S-transferase gene family as part of the lipid-protein enzyme complex. Experiments are proposed to complete the model of the VKOR enzyme complex and unveil the basis for genetic resistance to warfarin. Recombinant VKOR will be used to increase the capacity of cell lines to produce functional clotting factors VII and IX. It is our hypothesis that vitamin KH2 cofactor production by VKOR is a limiting factor in cellular production of these recombinant proteins. Although 8-10 different vitamin K-dependent proteins have been shown to be made extrahepatically only some have been identified. They include the coagulation factors prothrombin and protein S, the growth arrest specific gene 6 product Gas6 and the bone and cartilage resident proteins, osteocalsin and matrix GLA protein (MGP). In the last specific aim of this application experiments are proposed to identify new vitamin K-dependent proteins by vitamin K-dependent radioactive labeling. The proposed experiments will provide a better understanding of vitamin K metabolism and vitamin K function and have an impact on prophylactic medicine concerned with recombinant vitamin K-dependent coagulation factors and warfarin anticoagulation. The experiments should also contribute to the exciting, rapidly expanding area of research on extra-hepatic vitamin K-dependent proteins. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: VITAMIN DEVELOPMENT
K-DEPENDENT
PROTEINS
IN
BLOOD
AND
Principal Investigator & Institution: Roth, David A.; Assistant Professor of Medicine; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215 Timing: Fiscal Year 2001; Project Start 01-SEP-1997; Project End 28-FEB-2003 Summary: In what is the only known biological process dependent on vitamin K, the vitamin K-dependent lambda-glutamyl carboxylase catalyzes the posttranslational
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modification of glutamate to lambda-carboxyglutamate in the vitamin K-dependent proteins during their synthesis. This modification is essential for the biological activities of all known vitamin K-dependent proteins. Substrates of the carboxylase include several proteins involved in blood coagulation as well as bone matrix proteins and Gas6. Gas6, a cell cycle regulated protein is a ligand for receptor tyrosine kinases and has been implicated in the prevention of apoptosis of growth arrested cells. While we have previously focused our studies on the role of vitamin K-dependent carboxylation in hemostasis, we have recently demonstrated extrahepatic expression of the vitamin Kdependent carboxylase gene in adult and embryonic rat tissues, supporting the hypothesis that vitamin K has an important physiological role outside of blood coagulation. Warfarin, a potent vitamin K antagonist, is a widely used anticoagulant which indirectly inhibits the activity of the vitamin K-dependent carboxylase. Warfarin is also a teratogen. Human maternal exposure to warfarin during pregnancy is associated with developmental abnormalities in the fetus, the warfarin embryopathy, suggesting critical developmental functions for the carboxylase enzyme and its substrates. New data from our laboratory demonstrates temporal variations in tissue specific expression of vitamin K-dependent carboxylase mRNA in developing rat embryonic tissues, supporting the hypothesis that vitamin K-dependent carboxylation is a developmentally regulated posttranslational modification important for normal embryogenesis. In the current application, studies are proposed to clarify the role of vitamin K in development by examining the developmental and tissue specific expression of the vitamin K-dependent carboxylase in rat embryos. The regulation of vitamin K-dependent carboxylase gene transcription will be evaluated in vitro to study the factors that regulate vitamin K- dependent protein activity during development. An animal model of warfarin embryopathy will be developed, to direct future in vivo studies for testing the functions of carboxylase substrates in development of the normal embryo. Vitamin K-dependent carboxylation will serve as a model for other developmentally regulated posttranslational modifications of proteins important in fetal development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: VITAMIN K-DEPENDENT TRANSMEMBRANE GLA PROTEINS Principal Investigator & Institution: Davie, Earl W.; Professor and Chairman; Biochemistry; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2003; Project Start 15-DEC-2002; Project End 30-NOV-2007 Summary: (provided by applicant): Vitamin K-dependent proteins have been shown to play a major role in vertebrates in blood coagulation and its regulation, as well as in bone resorption and tissue mineralization. The vitamin K-dependent proteins contain gamma carboxyglutamic acid residues that are generated in a post-translation event within the lumen of the endoplasmic reticulum. This reaction is catalyzed by a gamma glutamyl carboxylase that is widely distributed in numerous vertebrate and nonvertebrate tissues. This investigation will focus on gaining insight into the biological role of four novel vitamin K-dependent proteins that are single transmembrane proteins. These proteins range in size from 17 kDa to 25 kDa and contain from nine to thirteen gammacarboxyglutamic acid residues. They have been called PRGP1, PRGP2, TMG3, and TMG4. Genes for two of these transmembrane proteins, PRGP1 and TMG3 are located on the X chromosome, while genes for PRGP2 and TMG4 are found on chromosome 19 and 11, respectively. Studies with transfected mammalian cells have now shown that they require vitamin K for their post-translational modification in a reaction that is inhibited by warfarin. The carboxyl region of the four transmembrane
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Warfarin
proteins bind to Nedd4-like proteins, suggesting that they may play a role in the ubiquitin cycle. Nedd4-like proteins have a C2 domain, two to four WW domains, and a HECT domain that functions as an E3 ubiquitin ligase in the ubiquitin cycle. The mechanism and specificity of these reactions will be examined in detail in these investigations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: WAFARIN ASPIRIN RECURRENT STROKE STDY--WARSS & HEMOSTATISTIC SYS ACT SUBSTDY Principal Investigator & Institution: Kistler, John; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2001 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: WARFARIN ANTIPLATELET RECURRENT STROKE STUDY Principal Investigator & Institution: Mohr, Jay P.; Sciarra Professor; Neurology; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2001; Project Start 13-JUL-1992; Project End 30-JUN-2002 Summary: This proposal is a competitive renewal for an investigator-initiated, randomize, double-blind, multicenter, clinical trial currently testing the primary null hypothesis that, up to two years, warfarin and aspirin therapy will not differ in the frequency of death or ischemic stroke recurrence. Secondary null hypotheses are that warfarin and aspirin therapy will not differ in frequency of death or ischemic stroke recurrence over one year; that the effect of warfarin therapy, compared to aspirin, on death or stroke recurrence, will not be modified by baseline stroke severity, baseline stroke subtype, baseline lesion size, location of baseline infarct, ethnicity, gender, and age; and that warfarin and aspirin therapy will not differ in frequency of complications. Aspirin 325 mg daily is the platelet antiaggregant. Warfarin dose is adjusted to keep the INR at 1.4 to 2.8. Patients with ischemic stroke due to cardiac embolism or treated by endarterectomy are ineligible. Patients are randomized within 30 days after stroke and treated for up to two years, followed monthly by phone and quarterly in person to regulate the hematologic effects of medication and to detect the primary endpoints of death and symptomatic stroke recurrence, and to detect complications of therapy. To maintain blinding, the laboratory data are sent to the Data Management Center. PT/INR results sent to the local centers are correct for patients on active warfarin but are falsified for those on aspirin. An emergency notification system helps maintain patient safety. Through 24-Oct-1996 1603 patients have been recruited from 49 participating centers toward the 1,920 patient sample size. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: WARFARIN ANTIPLATELET RECURRENT STROKE STUDY Principal Investigator & Institution: Pettigrew, Jimmi L.; University of Kentucky 109 Kinkead Hall Lexington, Ky 40506 Timing: Fiscal Year 2001 Summary: To compare the effectiveness of warfarin versus a medication that inhibits platelet aggregation (aspirin) as post-stroke treatment, analyzing frequency of death, stroke recurrence, and safety over a two-year period.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: WARFARIN ASPIRIN RECURRENT STROKE STUDY Principal Investigator & Institution: Winkelman, Marc D.; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2001 Summary: An investigator initiated, randomized, double-blind, multi-center, clinical trial designed to test the primary null hypothesis that warfarin therapy will not reduce the frequency of death or ischemic stroke recurrence by 30% compared with aspirin therapy. The trial will also test that the rate of death and recurrent stroke with warfarin will not be 50% lower in one year compared with aspirin therapy; there will be no differences between the two therapies in the frequency of recurrence by stroke severity or subtype, race or sex. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: WARFARIN ASPIRIN RECURRENT STROKE STUDY Principal Investigator & Institution: Fisher, Mark; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2001 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: WARFARIN INDUCED VIT K INSUFFICIENCY EFFECTS ON BONE MASS & SKELETAL TURNOVER Principal Investigator & Institution: Binkley, Neil C.; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2001 Summary: OBJECTIVE To assess the effect of therapeutic warfarin administration upon markers of skeletal turnover and bone mineral density in rhesus monkeys. RESULTS Preliminary data observe no effect upon bone mass measured by dual energy X-ray absorptiometry or upon markers of skeletal turnover. FUTURE DIRECTIONS It is necessary to continue this project for the planned duration to assess the effect of long term anticoagulation in healthy animals which closely model human skeletal physiology. KEY WORDS osteoporosis, anticoagulation, vitamin K, skeletal turnover FUNDING Department of Medicine (Geriatrics Section), NIH RR00167, and NIA AG00801-01A1. PUBLICATIONS Binkley, N., Krueger, D., Todd, H., & Suttie, J. 1998 Skeletal Status Assessment in Male Rhesus Monkeys Receiving Warfarin. Bone, 23(5 suppl) S302. [A] Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: WARFARIN THERAPY USING COMPUTER ASSISTED GUIDANCE Principal Investigator & Institution: Wurster, Mark W.; Standing Stone, Inc. 191 Post Rd West Westport, Ct 06880 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 28-FEB-2003 Summary: (provided by applicant): The objective of this study is to evaluate a new approach to anticoagulation therapy, utilizing a unique software application and workflow redesign. Anticoagulation therapy, as it is currently administered in the
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United States, too often fails to achieve therapeutic goals, while giving rise to a large number of potentially preventable medical complications. Improvements in quality of care and clinical outcomes have been demonstrated by the use of specialized anticoagulation clinics. Implementation of these clinics, however, has been severely limited by their expense and the degree of subspecialty expertise required. The approach to be evaluated utilizes a software application that enables a subspecialty level of care to be rendered in a primary care setting, combined with changes in workflow that simultaneously improve financial performance. The activities outlined in Phase 1 are designed to measure the impact of this combination on the administration of anticoagulation therapy in a primary care setting, with attention to quality of care indicators and financial performance. Phase 2 will expand the use of this approach in an integrated fashion to multiple primary care sites as well as emergency departments and inpatient settings. Phase 2 will monitor indicators similar to those of Phase 1, as well as the use of this approach to facilitate outpatient treatment of deep venous thrombosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: WARFARIN VS ASPIRIN FOR INTRACRANIAL ARTERIAL STENOSIS Principal Investigator & Institution: Chimowitz, Marc I.; Neurology; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2001; Project Start 25-SEP-1998; Project End 31-JUL-2003 Summary: Background and Relevance. Atherosclerotic stenosis of the major intracranial arteries causes 40,000 strokes per year in the USA, costing the country at least 600,000,000 dollars annually. There have been no prospective trials evaluating optimal medical therapy for this disease. The main objective of this clinical trial is to compare warfarin (INR 2-3) with aspirin (1300 mg/day) for preventing stroke (ischemic and hemorrhagic) and vascular death in patients with symptomatic stenosis of a major intracranial artery. Study Design. Prospective, randomized, double-blind, multi-center trial. The sample size required will be 403 patients per group (based on stroke and vascular death rates of 33 percent/3 years in the aspirin group vs 22 percent/3 years in the warfarin group, an alpha of 0.05, beta of 0.80, a 24 percent withdrawal of therapy rate, and a 1 percent drop out rate). Conduct of Trial. Patients with transient ischemic attack (TIA) or stroke caused by angiographically proven stenosis (greater than or equal to 50 percent) of a major intracranial artery will be randomized to warfarin or aspirin. The dose of warfarin will be adjusted to maintain the INR between 2-3 based on monthly blood tests. Patients will be contacted monthly by phone and examined every four months (mean follow-up of 3 years) to determine whether any endpoints have occurred. The primary analysis will compare the rates of stroke (ischemic and hemorrhagic) and vascular death in the two treatment groups. Secondary analyses will compare the two treatment groups with respect to rates of i) all vascular deaths and disabling stroke, ii) all stroke (ischemic and hemorrhagic), iii) fatal and nonfatal ischemic stroke, iv) all ischemic stroke, myocardial infarction and vascular death, v) all major systemic and any intracranial hemorrhage, vi) all ischemic stroke in the territory of the stenotic intracranial artery. Conclusion. This study will 1) define optimal medical therapy for patients with symptomatic intracranial arterial stenosis, and 2) identify patients whose rate of ischemic stroke in the territory of the stenotic intracranial artery on best medical therapy is sufficiently high (i.e., greater than or equal to 6 percent per year) to justify a subsequent trial comparing intracranial angioplasty with best medical therapy in these patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: WARFARIN VS ASPIRIN FOR SYMPTOMATIC INTRACRANIAL DISEASE Principal Investigator & Institution: Hemphill, Jesse C.; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2001; Project Start 01-DEC-2000; Project End 30-NOV-2001 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: WARFARIN VS ASPIRIN IN REDUCED EJECTION FRACTION STAT Principal Investigator & Institution: Thompson, John L.; Biostatistics; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-JUL-2006 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: WARFARIN VS ASPIRIN IN REDUCED EJECTION FRACTION-CLIN Principal Investigator & Institution: Pullicino, Patrick M.; Professor and Chairman; Neurology and Neurosciences; Univ of Med/Dent Nj Newark Newark, Nj 07103 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-JUL-2006 Summary: This abstract is not available. 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 “warfarin” (or synonyms) into the search box. This search gives you access to fulltext articles. The following is a sample of items found for warfarin in the PubMed Central database: •
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Apparent interaction between warfarin and levonorgestrel used for emergency contraception. by Ellison J, Thomson AJ, Greer IA, Walker ID.; 2000 Dec 2; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27541
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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Dichotomal Effect of the Coumadin Derivative Warfarin on Inflammatory Signal Transduction. by Kater AP, Peppelenbosch MP, Brandjes DP, Lumbantobing M.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130100
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Drug advisory: the interaction between warfarin and vaginal miconazole. by Wooltorton E.; 2001 Oct 2; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=81517
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Interaction between warfarin and topical miconazole cream. by Devaraj A, O'Beirne JP, Veasey R, Dunk AA.; 2002 Jul 13; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=117127
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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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Long-term, low-intensity warfarin after idiopathic venous thromboembolism. by Hackam DG.; 2003 Apr 29; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153690
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Microbial transformations of warfarin: stereoselective reduction by Nocardia corallina and Arthrobacter species. by Davis PJ, Rizzo JD.; 1982 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=241936
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Natural selection mapping of the warfarin-resistance gene. by Kohn MH, Pelz HJ, Wayne RK.; 2000 Jul 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=16644
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Physicians' perceptions of the benefits and risks of warfarin for patients with nonvalvular atrial fibrillation. by Bungard TJ, Ghali WA, McAlister FA, Buchan AM, Cave AJ, Hamilton PG, Mitchell LB, Shuaib A, Teo KK, Tsuyuki RT.; 2001 Aug 7; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=81330
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Protocol for Birmingham Atrial Fibrillation Treatment of the Aged study (BAFTA): a randomised controlled trial of warfarin versus aspirin for stroke prevention in the management of atrial fibrillation in an elderly primary care population [ISRCTN89345269]. by Mant JW, Richards SH, Hobbs FD, Fitzmaurice D, Lip GY, Murray E, Banting M, Fletcher K, Rahman J, Allan T, Raftery J, Bryan S.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=201020
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Warfarin, acetylsalicylic acid or both? by Hoey J.; 2002 Oct 29; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=134184
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 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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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 warfarin, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “warfarin” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for warfarin (hyperlinks lead to article summaries): •
A Bayesian method based on clotting factor activity for the prediction of maintenance warfarin dosage regimens. Author(s): Pitsiu M, Parker EM, Aarons L, Rowland M. Source: Therapeutic Drug Monitoring. 2003 February; 25(1): 36-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12548142&dopt=Abstract
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A case report of a spinal epidural haematoma associated with warfarin therapy. Author(s): Prasad SS, O'Malley M, Machani B, Shackleford IM. Source: Annals of the Royal College of Surgeons of England. 2003 July; 85(4): 277-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12855034&dopt=Abstract
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A comparison of corticosteroid and warfarin therapy in IgA nephropathy with crescent formation: preliminary trial. Author(s): Kanno Y, Witt M, Okada H, Nemoto H, Sugahara S, Nakamoto H, Suzuki H. Source: Clinical and Experimental Nephrology. 2003 March; 7(1): 48-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14586743&dopt=Abstract
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A comparison of heparin/warfarin and enoxaparin thromboprophylaxis in spinal cord injury: the Sheffield experience. Author(s): Thumbikat P, Poonnoose PM, Balasubrahmaniam P, Ravichandran G, McClelland MR. Source: Spinal Cord : the Official Journal of the International Medical Society of Paraplegia. 2002 August; 40(8): 416-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12124668&dopt=Abstract
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A comparison of the efficacy and rate of response to oral and intravenous Vitamin K in reversal of over-anticoagulation with warfarin. Author(s): Watson HG, Baglin T, Laidlaw SL, Makris M, Preston FE. Source: British Journal of Haematology. 2001 October; 115(1): 145-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11722425&dopt=Abstract
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A comparison of two intensities of warfarin for the prevention of recurrent thrombosis in patients with the antiphospholipid antibody syndrome. Author(s): Crowther MA, Ginsberg JS, Julian J, Denburg J, Hirsh J, Douketis J, Laskin C, Fortin P, Anderson D, Kearon C, Clarke A, Geerts W, Forgie M, Green D, Costantini L, Yacura W, Wilson S, Gent M, Kovacs MJ. Source: The New England Journal of Medicine. 2003 September 18; 349(12): 1133-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13679527&dopt=Abstract
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A comparison of warfarin and aspirin for the prevention of recurrent ischemic stroke. Author(s): Mohr JP, Thompson JL, Lazar RM, Levin B, Sacco RL, Furie KL, Kistler JP, Albers GW, Pettigrew LC, Adams HP Jr, Jackson CM, Pullicino P; Warfarin-Aspirin Recurrent Stroke Study Group. Source: The New England Journal of Medicine. 2001 November 15; 345(20): 1444-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11794192&dopt=Abstract
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A prospective randomized trial of aspirin-clopidogrel combination therapy and doseadjusted warfarin on indices of thrombogenesis and platelet activation in atrial fibrillation. Author(s): Kamath S, Blann AD, Chin BS, Lip GY. Source: Journal of the American College of Cardiology. 2002 August 7; 40(3): 484-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12142115&dopt=Abstract
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A protocol of urokinase infusion and warfarin for the management of the thrombosed haemodialysis catheter. Author(s): Webb A, Abdalla M, Russell GI. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2001 October; 16(10): 2075-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11572900&dopt=Abstract
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A randomized trial of initial warfarin dosing based on simple clinical criteria. Author(s): Shine D, Patel J, Kumar J, Malik A, Jaeger J, Maida M, Ord L, Burrows G. Source: Thrombosis and Haemostasis. 2003 February; 89(2): 297-304. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12574810&dopt=Abstract
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A randomized trial of minidose warfarin for the prevention of late malfunction in tunneled, cuffed hemodialysis catheters. Author(s): Mokrzycki MH, Jean-Jerome K, Rush H, Zdunek MP, Rosenberg SO. Source: Kidney International. 2001 May; 59(5): 1935-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11318966&dopt=Abstract
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A review of anticoagulation with warfarin in patients with nonvalvular atrial fibrillation. Author(s): Abdelhafiz AH. Source: Clinical Therapeutics. 2001 October; 23(10): 1628-36. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11727726&dopt=Abstract
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Abdominal wall hematoma as a complication of warfarinization. Author(s): Kao CL, Chang JP. Source: The Journal of Emergency Medicine. 2001 April; 20(3): 293. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11267821&dopt=Abstract
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Absence of an interaction between the synthetic pentasaccharide fondaparinux and oral warfarin. Author(s): Faaij RA, Burggraaf J, Schoemaker RC, Van Amsterdam RG, Cohen AF. Source: British Journal of Clinical Pharmacology. 2002 September; 54(3): 304-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12236851&dopt=Abstract
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Action of dipyridamole and warfarin on growth of human endothelial cells cultured in serum-free media. Author(s): Liem LK, Choong LH, Woo KT. Source: Clinical Biochemistry. 2001 March; 34(2): 141-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11311224&dopt=Abstract
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American Heart Association/American College of Cardiology Foundation guide to warfarin therapy. Author(s): Hirsh J, Fuster V, Ansell J, Halperin JL; American Heart Association/American College of Cardiology Foundation. Source: Journal of the American College of Cardiology. 2003 May 7; 41(9): 1633-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12742309&dopt=Abstract
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American Heart Association/American College of Cardiology Foundation guide to warfarin therapy. Author(s): Hirsh J, Fuster V, Ansell J, Halperin JL; American Heart Association; American College of Cardiology Foundation. Source: Circulation. 2003 April 1; 107(12): 1692-711. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12668507&dopt=Abstract
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An adverse interaction between warfarin and capecitabine: a case report and review of the literature. Author(s): Copur MS, Ledakis P, Bolton M, Morse AK, Werner T, Norvell M, Muhvic J, Chu E. Source: Clinical Colorectal Cancer. 2001 November; 1(3): 182-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12450435&dopt=Abstract
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An approach for the quantitative consideration of genetic polymorphism data in chemical risk assessment: examples with warfarin and parathion. Author(s): Gentry PR, Hack CE, Haber L, Maier A, Clewell HJ 3rd. Source: Toxicological Sciences : an Official Journal of the Society of Toxicology. 2002 November; 70(1): 120-39. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12388841&dopt=Abstract
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Antibacterial prescribing and warfarin: a review. Author(s): Rice PJ, Perry RJ, Afzal Z, Stockley IH. Source: British Dental Journal. 2003 April 26; 194(8): 411-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12778089&dopt=Abstract
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Anticoagulation for prosthetic heart valves during pregnancy: the importance of warfarin daily dose. Author(s): Vitale N, De Feo M, Cotrufo M. Source: European Journal of Cardio-Thoracic Surgery : Official Journal of the European Association for Cardio-Thoracic Surgery. 2002 October; 22(4): 656; Author Reply 657. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12297198&dopt=Abstract
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Anticoagulation with anisindione in a patient with a warfarin-induced skin eruption. Author(s): Spyropoulos AC, Hayth KA, Jenkins P. Source: Pharmacotherapy. 2003 April; 23(4): 533-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12680483&dopt=Abstract
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Anticoagulation with warfarin in pediatrics. Author(s): Desai H, Farrington E. Source: Pediatric Nursing. 2000 March-April; 26(2): 199-203. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12026277&dopt=Abstract
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Anticoagulation with warfarin. A review of monitoring issues. Author(s): Vogel E. Source: Adv Nurse Pract. 2001 January; 9(1): 75-8, 81, 94. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12416044&dopt=Abstract
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Apparent warfarin potency inconsistencies compromise effectiveness. Author(s): Rothschild BM. Source: Archives of Internal Medicine. 2003 May 26; 163(10): 1243; Author Reply 1244. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12767972&dopt=Abstract
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Aspirin and warfarin equally good for stroke patients. Author(s): Gottlieb S. Source: Bmj (Clinical Research Ed.). 2001 November 24; 323(7323): 1204. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11719405&dopt=Abstract
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Aspirin or warfarin: what's best after a heart attack? Risk of bleeding counters warfarin's edge in efficacy. Author(s): Ornato JP. Source: Health News. 2002 November; 8(11): 3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12523247&dopt=Abstract
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Aspirin, warfarin, or the combination for secondary prevention of coronary events in patients with acute coronary syndromes and prior coronary artery bypass surgery. Author(s): Huynh T, Theroux P, Bogaty P, Nasmith J, Solymoss S. Source: Circulation. 2001 June 26; 103(25): 3069-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11425770&dopt=Abstract
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Assessment of an age-adjusted warfarin initiation protocol. Author(s): Roberts GW, Helboe T, Nielsen CB, Gallus AS, Jensen I, Cosh DG, Eaton VS. Source: The Annals of Pharmacotherapy. 2003 June; 37(6): 799-803. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12773064&dopt=Abstract
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Association between CYP2C9 genetic variants and anticoagulation-related outcomes during warfarin therapy. Author(s): Higashi MK, Veenstra DL, Kondo LM, Wittkowsky AK, Srinouanprachanh SL, Farin FM, Rettie AE. Source: Jama : the Journal of the American Medical Association. 2002 April 3; 287(13): 1690-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11926893&dopt=Abstract
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Beriplex P/N reverses severe warfarin-induced overanticoagulation immediately and completely in patients presenting with major bleeding. Author(s): Evans G, Luddington R, Baglin T. Source: British Journal of Haematology. 2001 December; 115(4): 998-1001. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11843839&dopt=Abstract
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Bevacizumab, bleeding, thrombosis, and warfarin. Author(s): Kilickap S, Abali H, Celik I. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 September 15; 21(18): 3542; Author Reply 3543. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12972536&dopt=Abstract
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Bisoprolol: studies of potential interactions with theophylline and warfarin in healthy volunteers. Author(s): Warrington SJ, Johnston A, Lewis Y, Murphy M. Source: Journal of Cardiovascular Pharmacology. 1990; 16 Suppl 5: S164-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11527121&dopt=Abstract
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Bleeding associated with doxycycline and warfarin treatment. Author(s): Baciewicz AM, Bal BS. Source: Archives of Internal Medicine. 2001 May 14; 161(9): 1231. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11343446&dopt=Abstract
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Bosentan and warfarin interaction. Author(s): Murphey LM, Hood EH. Source: The Annals of Pharmacotherapy. 2003 July-August; 37(7-8): 1028-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12841813&dopt=Abstract
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Can a simple warfarin initiation scheme predict the maintenance dose in patients with nonrheumatic atrial fibrillation? Author(s): Culhane NS. Source: The Journal of Family Practice. 2002 February; 51(2): 175. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11978219&dopt=Abstract
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Can warfarin be continued during dental extraction? Results of a randomized controlled trial. Author(s): Evans IL, Sayers MS, Gibbons AJ, Price G, Snooks H, Sugar AW. Source: The British Journal of Oral & Maxillofacial Surgery. 2002 June; 40(3): 248-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12054719&dopt=Abstract
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Capecitabine-induced potentiation of warfarin. Author(s): Buyck HC, Buckley N, Leslie MD, Plowman PN. Source: Clin Oncol (R Coll Radiol). 2003 August; 15(5): 297. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12924461&dopt=Abstract
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Chiral CE separation of warfarin in albumin containing samples. Author(s): Yau WP, Chan E. Source: Journal of Pharmaceutical and Biomedical Analysis. 2002 April 1; 28(1): 107-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11861114&dopt=Abstract
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Clinical observations with the amiodarone/warfarin interaction: dosing relationships with long-term therapy. Author(s): Sanoski CA, Bauman JL. Source: Chest. 2002 January; 121(1): 19-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11796427&dopt=Abstract
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Clinical predictors of prolonged delay in return of the international normalized ratio to within the therapeutic range after excessive anticoagulation with warfarin. Author(s): Hylek EM, Regan S, Go AS, Hughes RA, Singer DE, Skates SJ. Source: Annals of Internal Medicine. 2001 September 18; 135(6): 393-400. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11560452&dopt=Abstract
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Coagulation status using thromboelastography in patients receiving warfarin prophylaxis and epidural analgesia. Author(s): Hepner DL, Concepcion M, Bhavani-Shankar K. Source: Journal of Clinical Anesthesia. 2002 September; 14(6): 405-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12393106&dopt=Abstract
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Comment: other factors should be considered in a possible warfarin and sulfasalazine interaction. Author(s): Sherman JJ. Source: The Annals of Pharmacotherapy. 2001 April; 35(4): 506. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11302418&dopt=Abstract
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Comment: patient-specific factors predictive of warfarin dosage requirements. Author(s): Lindh JD. Source: The Annals of Pharmacotherapy. 2003 March; 37(3): 454; Author Reply 454. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12639185&dopt=Abstract
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Comparison of 10-mg and 5-mg warfarin initiation nomograms together with lowmolecular-weight heparin for outpatient treatment of acute venous thromboembolism. A randomized, double-blind, controlled trial. Author(s): Kovacs MJ, Rodger M, Anderson DR, Morrow B, Kells G, Kovacs J, Boyle E, Wells PS. Source: Annals of Internal Medicine. 2003 May 6; 138(9): 714-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12729425&dopt=Abstract
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Comparison of a daily fixed 2.5-mg warfarin dose with a 5-mg, international normalized ratio adjusted, warfarin dose initially following heart valve replacement. Author(s): Ageno W, Turpie AG, Steidl L, Ambrosini F, Cattaneo R, Codari RL, Nardo B, Venco A. Source: The American Journal of Cardiology. 2001 July 1; 88(1): 40-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11423056&dopt=Abstract
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Comparison of a nomogram and physician-adjusted dosage of warfarin for prophylaxis against deep-vein thrombosis after arthroplasty. Author(s): Anderson DR, Wilson SJ, Blundell J, Petrie D, Leighton R, Stanish W, Alexander D, Robinson KS, Burton E, Gross M. Source: The Journal of Bone and Joint Surgery. American Volume. 2002 November; 84A(11): 1992-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12429760&dopt=Abstract
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Comparison of low-intensity warfarin therapy with conventional-intensity warfarin therapy for long-term prevention of recurrent venous thromboembolism. Author(s): Kearon C, Ginsberg JS, Kovacs MJ, Anderson DR, Wells P, Julian JA, MacKinnon B, Weitz JI, Crowther MA, Dolan S, Turpie AG, Geerts W, Solymoss S, van Nguyen P, Demers C, Kahn SR, Kassis J, Rodger M, Hambleton J, Gent M; Extended Low-Intensity Anticoagulation for Thrombo-Embolism Investigators. Source: The New England Journal of Medicine. 2003 August 14; 349(7): 631-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12917299&dopt=Abstract
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Comparison of low-molecular-weight heparin and warfarin for the secondary prevention of venous thromboembolism in patients with cancer: a randomized controlled study. Author(s): Meyer G, Marjanovic Z, Valcke J, Lorcerie B, Gruel Y, Solal-Celigny P, Le Maignan C, Extra JM, Cottu P, Farge D. Source: Archives of Internal Medicine. 2002 August 12-26; 162(15): 1729-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12153376&dopt=Abstract
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Comparison of two aspirin doses on ischemic stroke in post-myocardial infarction patients in the warfarin (Coumadin) Aspirin Reinfarction Study (CARS). Author(s): O'Connor CM, Gattis WA, Hellkamp AS, Langer A, Larsen RL, Harrington RA, Berkowitz SD, O'Gara PT, Kopecky SL, Gheorghiade M, Daly R, Califf RM, Fuster V. Source: The American Journal of Cardiology. 2001 September 1; 88(5): 541-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11524065&dopt=Abstract
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Comparison of ximelagatran with warfarin for the prevention of venous thromboembolism after total knee replacement. Author(s): Francis CW, Berkowitz SD, Comp PC, Lieberman JR, Ginsberg JS, Paiement G, Peters GR, Roth AW, McElhattan J, Colwell CW Jr; EXULT A Study Group. Source: The New England Journal of Medicine. 2003 October 30; 349(18): 1703-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14585938&dopt=Abstract
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Complications of preinjury warfarin use in the trauma patient. Author(s): Mina AA, Bair HA, Howells GA, Bendick PJ. Source: The Journal of Trauma. 2003 May; 54(5): 842-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12777897&dopt=Abstract
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Complications of warfarin therapy: causes, costs, and the role of the anticoagulation clinic. Author(s): Hamby L, Weeks WB, Malikowski C. Source: Effective Clinical Practice : Ecp. 2000 July-August; 3(4): 179-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11183433&dopt=Abstract
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Conformational stability and warfarin-binding properties of human serum albumin studied by recombinant mutants. Author(s): Watanabe H, Kragh-Hansen U, Tanase S, Nakajou K, Mitarai M, Iwao Y, Maruyama T, Otagiri M. Source: The Biochemical Journal. 2001 July 1; 357(Pt 1): 269-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11415459&dopt=Abstract
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Continuation of medically necessary aspirin and warfarin during cutaneous surgery. Author(s): Otley CC. Source: Mayo Clinic Proceedings. 2003 November; 78(11): 1392-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14601698&dopt=Abstract
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Coroner highlights prescribing error after patient dies from warfarin overdose. Author(s): Eaton L. Source: Bmj (Clinical Research Ed.). 2002 October 26; 325(7370): 922. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12399335&dopt=Abstract
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Correction of INR by prothrombin complex concentrate and vitamin K in patients with warfarin related hemorrhagic complication. Author(s): Yasaka M, Sakata T, Minematsu K, Naritomi H. Source: Thrombosis Research. 2002 October 1; 108(1): 25-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12586128&dopt=Abstract
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Correction of warfarin-induced nasal hypoplasia. Author(s): Bradley JP, Kawamoto HK, Taub P. Source: Plastic and Reconstructive Surgery. 2003 April 15; 111(5): 1680-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12655214&dopt=Abstract
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Crystal structure analysis of warfarin binding to human serum albumin: anatomy of drug site I. Author(s): Petitpas I, Bhattacharya AA, Twine S, East M, Curry S. Source: The Journal of Biological Chemistry. 2001 June 22; 276(25): 22804-9. Epub 2001 April 02. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11285262&dopt=Abstract
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Crystal structure of human cytochrome P450 2C9 with bound warfarin. Author(s): Williams PA, Cosme J, Ward A, Angove HC, Matak Vinkovic D, Jhoti H. Source: Nature. 2003 July 24; 424(6947): 464-8. Epub 2003 Jul 13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12861225&dopt=Abstract
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Cutaneous surgery in patients receiving warfarin therapy. Author(s): Alcalay J. Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 2001 August; 27(8): 756-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11493301&dopt=Abstract
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CYP2C9 exon 4 mutations and warfarin dose phenotype in Asians. Author(s): Rettie AE, Tai G, Veenstra DL, Farin FM, Srinouanprachan S, Lin YS, Thummel KE, Hines RN. Source: Blood. 2003 April 1; 101(7): 2896-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12642346&dopt=Abstract
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CYP2C9 polymorphism and warfarin dose requirements. Author(s): Daly AK, Day CP, Aithal GP. Source: British Journal of Clinical Pharmacology. 2002 April; 53(4): 408-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11966680&dopt=Abstract
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Dalteparin as periprocedure anticoagulation for patients on warfarin and at high risk of thrombosis. Author(s): Tinmouth AH, Morrow BH, Cruickshank MK, Moore PM, Kovacs MJ. Source: The Annals of Pharmacotherapy. 2001 June; 35(6): 669-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11408982&dopt=Abstract
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Dalteparin vs warfarin in hip arthroplasty patients. Author(s): Bajjoka AE. Source: Archives of Internal Medicine. 2001 March 12; 161(5): 776-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11231726&dopt=Abstract
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Data plotting of warfarin binding to human serum albumin. Author(s): Pablo Villamor J, Zaton AM. Source: Journal of Biochemical and Biophysical Methods. 2001 March 28; 48(1): 33-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11282400&dopt=Abstract
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Department of Veterans Affairs Cooperative Studies Program Clinical Trial comparing combined warfarin and aspirin with aspirin alone in survivors of acute myocardial infarction: primary results of the CHAMP study. Author(s): Fiore LD, Ezekowitz MD, Brophy MT, Lu D, Sacco J, Peduzzi P; Combination Hemotherapy and Mortality Prevention (CHAMP) Study Group. Source: Circulation. 2002 February 5; 105(5): 557-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11827919&dopt=Abstract
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Design, progress and challenges of a double-blind trial of warfarin versus aspirin for symptomatic intracranial arterial stenosis. Author(s): Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) Trial Investigators. Source: Neuroepidemiology. 2003 March-April; 22(2): 106-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12656117&dopt=Abstract
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Determination of plasma prothrombin level by Ca2+-dependent prothrombin activator (CA-1) during warfarin anticoagulation. Author(s): Iwahashi H, Kimura M, Nakajima K, Yamada D, Morita T. Source: J Heart Valve Dis. 2001 May; 10(3): 388-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11380105&dopt=Abstract
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Development and validation of a sensitive and robust LC-tandem MS method for the analysis of warfarin enantiomers in human plasma. Author(s): Naidong W, Ring PR, Midtlien C, Jiang X. Source: Journal of Pharmaceutical and Biomedical Analysis. 2001 May; 25(2): 219-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11275431&dopt=Abstract
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Diarrhea-associated over-anticoagulation in a patient taking warfarin: therapeutic role of cholestyramine. Author(s): Roberge RJ, Rao P, Miske GR, Riley TJ. Source: Vet Hum Toxicol. 2000 December; 42(6): 351-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11111942&dopt=Abstract
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Differences in warfarin dosing decisions based on international normalized ratio measurements with two point-of-care testing devices and a reference laboratory measurement. Author(s): Shermock KM, Bragg L, Connor JT, Fink J, Mazzoli G, Kottke-Marchant K. Source: Pharmacotherapy. 2002 November; 22(11): 1397-404. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12432965&dopt=Abstract
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Difficulties in anticoagulation management during coadministration of warfarin and rifampin. Author(s): Lee CR, Thrasher KA. Source: Pharmacotherapy. 2001 October; 21(10): 1240-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11601670&dopt=Abstract
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Diminished anticoagulant effects of warfarin with concomitant mercaptopurine therapy. Author(s): Martin LA, Mehta SD. Source: Pharmacotherapy. 2003 February; 23(2): 260-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12587816&dopt=Abstract
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Divergent effects of raloxifene HCI on the pharmacokinetics and pharmacodynamics of warfarin. Author(s): Miller JW, Skerjanec A, Knadler MP, Ghosh A, Allerheiligen SR. Source: Pharmaceutical Research. 2001 July; 18(7): 1024-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11496940&dopt=Abstract
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Does anticoagulation do more harm than good?: A comparison of patients treated without prophylaxis and patients treated with low-dose warfarin after total knee arthroplasty. Author(s): Sachs RA, Smith JH, Kuney M, Paxton L. Source: The Journal of Arthroplasty. 2003 June; 18(4): 389-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12820078&dopt=Abstract
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Does PC-SPEs interact with warfarin? Author(s): Davis NB, Nahlik L, Vogelzang NJ. Source: The Journal of Urology. 2002 April; 167(4): 1793. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11912419&dopt=Abstract
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Duration of warfarin sodium therapy prior to electrical cardioversion of atrial fibrillation. Author(s): Ryman J, Frick M, Frykman V, Rosenqvist M. Source: Journal of Internal Medicine. 2003 January; 253(1): 76-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12588539&dopt=Abstract
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Effect of coenzyme Q10 and Ginkgo biloba on warfarin dosage in stable, long-term warfarin treated outpatients. A randomised, double blind, placebo-crossover trial. Author(s): Engelsen J, Nielsen JD, Winther K. Source: Thrombosis and Haemostasis. 2002 June; 87(6): 1075-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12083489&dopt=Abstract
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Effect of enoxaparin on homocysteine concentration in warfarin-treated patients. Author(s): Haviv Y, Lubetsky A, Sela BA, Ezra D, Olchovsky D. Source: The Annals of Pharmacotherapy. 2002 September; 36(9): 1355-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12196051&dopt=Abstract
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Effect of ibuprofen and warfarin on the allosteric properties of haem-human serum albumin. A spectroscopic study. Author(s): Baroni S, Mattu M, Vannini A, Cipollone R, Aime S, Ascenzi P, Fasano M. Source: European Journal of Biochemistry / Febs. 2001 December; 268(23): 6214-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11733017&dopt=Abstract
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Effect of levofloxacin coadministration on the international normalized ratios during warfarin therapy. Author(s): Yamreudeewong W, Lower DL, Kilpatrick DM, Enlow AM, Burrows MM, Greenwood MC. Source: Pharmacotherapy. 2003 March; 23(3): 333-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12627932&dopt=Abstract
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Effect of low-intensity warfarin therapy on left atrial thrombus resolution in patients with nonvalvular atrial fibrillation: a transesophageal echocardiographic study. Author(s): Kimura M, Wasaki Y, Ogawa H, Nakatsuka M, Wakeyama T, Iwami T, Ono K, Nakao F, Matsuzaki M. Source: Japanese Circulation Journal. 2001 April; 65(4): 271-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11316121&dopt=Abstract
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Effect of modafinil at steady state on the single-dose pharmacokinetic profile of warfarin in healthy volunteers. Author(s): Robertson P Jr, Hellriegel ET, Arora S, Nelson M. Source: Journal of Clinical Pharmacology. 2002 February; 42(2): 205-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11831544&dopt=Abstract
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Effect of prothrombin complex concentrate on INR and blood coagulation system in emergency patients treated with warfarin overdose. Author(s): Yasaka M, Oomura M, Ikeno K, Naritomi H, Minematsu K. Source: Annals of Hematology. 2003 February; 82(2): 121-3. Epub 2002 November 29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12601493&dopt=Abstract
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Effect of regimen complexity on patient satisfaction and compliance with warfarin therapy. Author(s): Hixson-Wallace JA, Dotson JB, Blakey SA. Source: Clinical and Applied Thrombosis/Hemostasis : Official Journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis. 2001 January; 7(1): 33-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11190902&dopt=Abstract
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Effect of soy milk on warfarin efficacy. Author(s): Ann Intern Med. 2002 Dec 3;137(11):I41 Source: The Annals of Pharmacotherapy. 2002 December; 36(12): 1893-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12459002
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Effect of stress on international normalized ratio during warfarin therapy. Author(s): Hawk TL, Havrda DE. Source: The Annals of Pharmacotherapy. 2002 April; 36(4): 617-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11918508&dopt=Abstract
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Effect of the catechol-O-methyltransferase inhibitor entacapone on the steady-state pharmacokinetics and pharmacodynamics of warfarin. Author(s): Dingemanse J, Meyerhoff C, Schadrack J. Source: British Journal of Clinical Pharmacology. 2002 May; 53(5): 485-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11994054&dopt=Abstract
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Effect of tolterodine on the anticoagulant actions and pharmacokinetics of singledose warfarin in healthy volunteers. Author(s): Rahimy M, Hallen B, Narang P. Source: Arzneimittel-Forschung. 2002; 52(12): 890-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12572529&dopt=Abstract
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Effect of warfarin therapy on bleeding during cataract surgery. Author(s): Rotenstreich Y, Rubowitz A, Segev F, Jaeger-Roshu S, Assia EI. Source: Journal of Cataract and Refractive Surgery. 2001 September; 27(9): 1344-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11566514&dopt=Abstract
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Effects of fixed low-dose warfarin on hemostatic factors in continuous ambulatory peritoneal dialysis patients. Author(s): Kim SB, Lee SK, Park JS, Chi HS, Hong CD, Yang WS. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 2001 February; 37(2): 343-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11157376&dopt=Abstract
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Effects of fixed low-dose warfarin, aspirin-warfarin combination therapy, and doseadjusted warfarin on thrombogenesis in chronic atrial fibrillation. Author(s): Li-Saw-Hee FL, Blann AD, Lip GY. Source: Stroke; a Journal of Cerebral Circulation. 2000 April; 31(4): 828-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10753983&dopt=Abstract
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Effects of low-dose warfarin and aspirin versus no treatment on stroke in a mediumrisk patient population with atrial fibrillation. Author(s): Edvardsson N, Juul-Moller S, Omblus R, Pehrsson K. Source: Journal of Internal Medicine. 2003 July; 254(1): 95-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12823646&dopt=Abstract
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Effects of oral vitamin K on S- and R-warfarin pharmacokinetics and pharmacodynamics: enhanced safety of warfarin as a CYP2C9 probe. Author(s): Kim JS, Nafziger AN, Gaedigk A, Dickmann LJ, Rettie AE, Bertino JS Jr. Source: Journal of Clinical Pharmacology. 2001 July; 41(7): 715-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11452703&dopt=Abstract
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Efficacy of intravenous vitamin K in a case of massive warfarin overdosage. Author(s): Kitchens CS. Source: Thrombosis and Haemostasis. 2001 August; 86(2): 719-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11522034&dopt=Abstract
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Emergency case. Head injury in patients using warfarin. Author(s): Fleming B. Source: Can Fam Physician. 2001 April; 47: 727-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11340752&dopt=Abstract
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Enzymatic shunting: resolving the acetaminophen-warfarin controversy. Author(s): Lehmann DE. Source: Pharmacotherapy. 2000 December; 20(12): 1464-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11130219&dopt=Abstract
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Evaluation of the clinical and economic impact of a brand name-to-generic warfarin sodium conversion program. Author(s): Witt DM, Tillman DJ, Evans CM, Plotkin TV, Sadler MA. Source: Pharmacotherapy. 2003 March; 23(3): 360-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12627935&dopt=Abstract
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Evaluation of very low-dose subcutaneous vitamin K during postoperative warfarin therapy. Author(s): Possidente CJ, Howe JG, Cushman M. Source: Pharmacotherapy. 2001 March; 21(3): 295-300. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11253854&dopt=Abstract
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Evidence for continuing warfarin during dental extractions. Author(s): Gibbons AJ, Sugar AW. Source: British Dental Journal. 2003 January 25; 194(2): 65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12596735&dopt=Abstract
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Extended outpatient therapy with low molecular weight heparin for the treatment of recurrent venous thromboembolism despite warfarin therapy. Author(s): Luk C, Wells PS, Anderson D, Kovacs MJ. Source: The American Journal of Medicine. 2001 September; 111(4): 270-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11566456&dopt=Abstract
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Extensive skin necrosis associated with warfarin sodium therapy. Author(s): Roche-Nagle G, Robb W, Ireland A, Bouchier-Hayes D. Source: European Journal of Vascular and Endovascular Surgery : the Official Journal of the European Society for Vascular Surgery. 2003 May; 25(5): 481-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12713792&dopt=Abstract
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External quality assessment for warfarin dosing using computerised decision support software. Author(s): Oppenkowski TP, Murray ET, Sandhar H, Fitzmaurice DA. Source: Journal of Clinical Pathology. 2003 August; 56(8): 605-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12890811&dopt=Abstract
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Extreme warfarin sensitivity in siblings associated with multiple cytochrome P450 polymorphisms. Author(s): Tabrizi AR, McGrath SD, Blinder MA, Buchman TG, Zehnbauer BA, Freeman BD. Source: American Journal of Hematology. 2001 June; 67(2): 144-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11343389&dopt=Abstract
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Factors affecting warfarin therapy following cardiac valve surgery. Author(s): Lee J, Lee B, Kim K, Ahn H, Suh O, Lee M, Shin W. Source: The Annals of Pharmacotherapy. 2002 December; 36(12): 1845-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12452742&dopt=Abstract
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Factors influencing the frequency of attendance at a warfarin dosing clinic. Author(s): Blann AD, Bareford D. Source: Clinical and Laboratory Haematology. 2001 June; 23(3): 205-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11553065&dopt=Abstract
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Fatal warfarin-induced skin necrosis after total hip arthroplasty. Author(s): Clark JA, Bremner BR. Source: The Journal of Arthroplasty. 2002 December; 17(8): 1070-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12478522&dopt=Abstract
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Fenofibrate and warfarin interaction. Author(s): Aldridge MA, Ito MK. Source: Pharmacotherapy. 2001 July; 21(7): 886-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11444587&dopt=Abstract
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Fenofibrate potentiates warfarin effects. Author(s): Kim KY, Mancano MA. Source: The Annals of Pharmacotherapy. 2003 February; 37(2): 212-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12549950&dopt=Abstract
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Fixed minidose versus-adjusted low-dose warfarin after total joint arthroplasty: a randomized prospective study. Author(s): Vives MJ, Hozack WJ, Sharkey PF, Moriarty L, Sokoloff B, Rothman RH. Source: The Journal of Arthroplasty. 2001 December; 16(8): 1030-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11740759&dopt=Abstract
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Fixed-dose versus adjusted-dose warfarin in patients with prosthetic heart valves in a peri-urban impoverished population. Author(s): Buchanan-Leel B, Levetan BN, Lombard CJ, Commerford PJ. Source: J Heart Valve Dis. 2002 July; 11(4): 583-92; Discussion 593. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12150309&dopt=Abstract
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Fluvoxamine interaction with warfarin. Author(s): Limke KK, Shelton AR, Elliott ES. Source: The Annals of Pharmacotherapy. 2002 December; 36(12): 1890-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12452751&dopt=Abstract
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Genetic mechanisms for hypersensitivity and resistance to the anticoagulant Warfarin. Author(s): Linder MW. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 2001 June; 308(1-2): 9-15. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11412812&dopt=Abstract
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Genetic modulation of oral anticoagulation with warfarin. Author(s): Margaglione M, Colaizzo D, D'Andrea G, Brancaccio V, Ciampa A, Grandone E, Di Minno G. Source: Thrombosis and Haemostasis. 2000 November; 84(5): 775-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11127854&dopt=Abstract
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Genetic polymorphism in exon 4 of cytochrome P450 CYP2C9 may be associated with warfarin sensitivity in Chinese patients. Author(s): Leung AY, Chow HC, Kwong YL, Lie AK, Fung AT, Chow WH, Yip AS, Liang R. Source: Blood. 2001 October 15; 98(8): 2584-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11588061&dopt=Abstract
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Genetic susceptibility to hemorrhagic complications during warfarin therapy. Author(s): Tabrizi AR, Freeman BD, Buchman TG, Zehnbauer BA. Source: Surgery. 2001 May; 129(5): 645-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11331459&dopt=Abstract
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Guidelines for warfarin therapy following a thromboembolic event. Author(s): Sutton SK. Source: Journal of General Internal Medicine : Official Journal of the Society for Research and Education in Primary Care Internal Medicine. 2001 May; 16(5): 347. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11359557&dopt=Abstract
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Heparin-induced thrombocytopenia and warfarin-induced skin necrosis in a child with severe protein C deficiency: successful treatment with dermatan sulfate and protein C concentrate. Author(s): Gatti L, Carnelli V, Rusconi R, Moia M. Source: Journal of Thrombosis and Haemostasis : Jth. 2003 February; 1(2): 387-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12871519&dopt=Abstract
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Hepatotoxic reaction to warfarin in a recovering hepatitis patient with hypoalbuminenia. Author(s): Bamanikar A, Hiremath S. Source: J Assoc Physicians India. 2002 November; 50: 1456. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12583490&dopt=Abstract
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Herbal drug curbicin and anticoagulant effect with and without warfarin: possibly related to the vitamin E component. Author(s): Yue QY, Jansson K. Source: Journal of the American Geriatrics Society. 2001 June; 49(6): 838. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11454132&dopt=Abstract
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High-performance liquid-chromatographic determination of warfarin enantiomers in plasma with automated on-line sample enrichment. Author(s): Boppana VK, Schaefer WH, Cyronak MJ. Source: Journal of Biochemical and Biophysical Methods. 2002 December 31; 54(1-3): 315-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12543507&dopt=Abstract
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Hospital admission due to warfarin potentiation by TMP-SMX. Author(s): Chafin CC, Ritter BA, James A, Self TH. Source: The Nurse Practitioner. 2000 December; 25(12): 73-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11149144&dopt=Abstract
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How safely and for how long can warfarin therapy be withheld in prosthetic heart valve patients hospitalized with a major hemorrhage? Author(s): Ananthasubramaniam K, Beattie JN, Rosman HS, Jayam V, Borzak S. Source: Chest. 2001 February; 119(2): 478-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11171726&dopt=Abstract
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Hypersensitivity to warfarin in a patient with a mechanical aortic prosthesis. Author(s): Tak T, Smith JF. Source: J Heart Valve Dis. 2001 November; 10(6): 832-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11767195&dopt=Abstract
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Implications of cytochrome P450 2C9 polymorphism on warfarin metabolism and dosing. Author(s): South Med J. 2001 Dec;94(12):1235 Source: Pharmacotherapy. 2001 February; 21(2): 235-42. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11817377
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Improving the safety profile of warfarin. Author(s): Chai SJ, Macik BG. Source: Semin Hematol. 2002 July; 39(3): 179-86. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12124680&dopt=Abstract
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In vitro stimulation of warfarin metabolism by quinidine: increases in the formation of 4'- and 10-hydroxywarfarin. Author(s): Ngui JS, Chen Q, Shou M, Wang RW, Stearns RA, Baillie TA, Tang W. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 2001 June; 29(6): 877-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11353757&dopt=Abstract
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Increased sensitivity to warfarin in elderly Hispanics. Author(s): Casner PR, Sandoval E. Source: Journal of Clinical Pharmacology. 2002 February; 42(2): 145-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11831536&dopt=Abstract
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Increased warfarin sensitivity as an early manifestation of occult prostate cancer with chronic disseminated intravascular coagulation. Author(s): Munter G, Hershko C. Source: Acta Haematologica. 2001; 105(2): 97-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11408712&dopt=Abstract
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Influence of CYP2C9 and CYP2C19 genetic polymorphisms on warfarin maintenance dose and metabolic clearance. Author(s): Scordo MG, Pengo V, Spina E, Dahl ML, Gusella M, Padrini R. Source: Clinical Pharmacology and Therapeutics. 2002 December; 72(6): 702-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12496751&dopt=Abstract
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Inhibition of warfarin activity by ribavirin. Author(s): Schulman S. Source: The Annals of Pharmacotherapy. 2002 January; 36(1): 72-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11816263&dopt=Abstract
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Inhibition of warfarin anticoagulation associated with chelation therapy. Author(s): Grebe HB, Gregory PJ. Source: Pharmacotherapy. 2002 August; 22(8): 1067-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12173793&dopt=Abstract
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Initiating warfarin therapy. Author(s): Dager WE. Source: The Annals of Pharmacotherapy. 2003 June; 37(6): 905-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12773083&dopt=Abstract
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Intentional overdose of warfarin in an adolescent: need for follow up. Author(s): Ramanan AV, Gissen P, Bose-Haider B. Source: Emergency Medicine Journal : Emj. 2002 January; 19(1): 90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11777896&dopt=Abstract
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Interaction between warfarin and danshen (Salvia miltiorrhiza). Author(s): Chan TY. Source: The Annals of Pharmacotherapy. 2001 April; 35(4): 501-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11302416&dopt=Abstract
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Interaction between warfarin and mango fruit. Author(s): Monterrey-Rodriguez J. Source: The Annals of Pharmacotherapy. 2002 May; 36(5): 940-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12014354&dopt=Abstract
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Interaction between warfarin and the herbal product quilinggao. Author(s): Wong AL, Chan TY. Source: The Annals of Pharmacotherapy. 2003 June; 37(6): 836-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12773074&dopt=Abstract
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Interaction between warfarin and topical miconazole cream. Author(s): Devaraj A, O'Beirne JP, Veasey R, Dunk AA. Source: Bmj (Clinical Research Ed.). 2002 July 13; 325(7355): 77. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12114237&dopt=Abstract
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Interaction of rofecoxib and celecoxib with warfarin. Author(s): Schaefer MG, Plowman BK, Morreale AP, Egan M. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 2003 July 1; 60(13): 1319-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12901032&dopt=Abstract
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Interactions of warfarin. Author(s): Rehulkova O. Source: Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2001 December; 145(2): 27-38. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12426769&dopt=Abstract
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Interindividual variability in sensitivity to warfarin--Nature or nurture? Author(s): Loebstein R, Yonath H, Peleg D, Almog S, Rotenberg M, Lubetsky A, Roitelman J, Harats D, Halkin H, Ezra D. Source: Clinical Pharmacology and Therapeutics. 2001 August; 70(2): 159-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11503010&dopt=Abstract
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International Normalized Ratio fluctuation with warfarin-fluorouracil therapy. Author(s): Carabino J, Wang F. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 2002 May 1; 59(9): 875. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12004471&dopt=Abstract
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Interpreting the International Normalized Ratio (INR) in individuals receiving argatroban and warfarin. Author(s): Sheth SB, DiCicco RA, Hursting MJ, Montague T, Jorkasky DK. Source: Thrombosis and Haemostasis. 2001 March; 85(3): 435-40. Erratum In: Thromb Haemost 2001 August; 86(2): 727. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11307810&dopt=Abstract
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Intraocular hemorrhages due to warfarin fluconazole drug interaction in a patient with presumed Candida endophthalmitis. Author(s): Mootha VV, Schluter ML, Das A. Source: Archives of Ophthalmology. 2002 January; 120(1): 94-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11786068&dopt=Abstract
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Is low-molecular-weight heparin safer than warfarin for secondary prevention of venous thromboembolism in cancer patients? Author(s): Caine GJ, Lip GY. Source: Archives of Internal Medicine. 2003 May 26; 163(10): 1243-4; Author Reply 1244. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12767973&dopt=Abstract
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Is warfarin really underused in patients with atrial fibrillation? Author(s): Weisbord SD, Whittle J, Brooks RC. Source: Journal of General Internal Medicine : Official Journal of the Society for Research and Education in Primary Care Internal Medicine. 2001 November; 16(11): 743-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11722687&dopt=Abstract
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Lack of pharmacokinetic interactions between argatroban and warfarin. Author(s): Brown PM, Hursting MJ. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 2002 November 1; 59(21): 2078-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12434720&dopt=Abstract
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Large left atrial thrombus formation despite warfarin therapy after device closure of a patent foramen ovale. Author(s): Cetta F, Arruda MJ, Graham LC. Source: Catheterization and Cardiovascular Interventions : Official Journal of the Society for Cardiac Angiography & Interventions. 2003 July; 59(3): 396-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12822169&dopt=Abstract
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Long term warfarin associated with bilateral blindness in a patient with atrial fibrillation and macular degeneration. Author(s): Ung T, James M, Gray RH. Source: Heart (British Cardiac Society). 2003 September; 89(9): 985. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12923003&dopt=Abstract
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Long term, low intensity warfarin helps against deep vein thrombosis. Author(s): Gottlieb S. Source: Bmj (Clinical Research Ed.). 2003 March 8; 326(7388): 516. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12623891&dopt=Abstract
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Long-term management of venous thromboembolism: is there a role for low-intensity warfarin therapy? Author(s): Eikelboom JW, Hankey GJ. Source: The Medical Journal of Australia. 2003 July 21; 179(2): 68-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12864713&dopt=Abstract
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Long-term warfarin and percutaneous intervention. Author(s): Vanderah S, Webb J. Source: J Invasive Cardiol. 2003 February; 15(2): 63-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12556616&dopt=Abstract
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Long-term, low-intensity warfarin therapy for the prevention of recurrent venous thromboembolism. Author(s): Ridker PM, Goldhaber SZ, Danielson E, Rosenberg Y, Eby CS, Deitcher SR, Cushman M, Moll S, Kessler CM, Elliott CG, Paulson R, Wong T, Bauer KA, Schwartz BA, Miletich JP, Bounameaux H, Glynn RJ; PREVENT Investigators. Source: The New England Journal of Medicine. 2003 April 10; 348(15): 1425-34. Epub 2003 February 24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12601075&dopt=Abstract
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Low dose, long-term warfarin safely prevents blood clots. Author(s): Levenson D. Source: Rep Med Guidel Outcomes Res. 2003 March 21; 14(6): 1-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12838964&dopt=Abstract
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Low-dose warfarin in rehabilitating stroke survivors. Author(s): Ginsberg JS, Bates SM, Oczkowski W, Booker N, Magier D, MacKinnon B, Weitz J, Kearon C, Cruickshank M, Julian JA, Gent M. Source: Thrombosis Research. 2002 September 15; 107(6): 287-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12565715&dopt=Abstract
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Low-intensity versus conventional-intensity warfarin for prevention of recurrent venous thromboembolism. Author(s): Malik V, Kupfer Y, Tessler S. Source: The New England Journal of Medicine. 2003 November 27; 349(22): 2164-7; Author Reply 2164-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14658127&dopt=Abstract
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Low-intensity versus conventional-intensity warfarin for prevention of recurrent venous thromboembolism. Author(s): Tran HA. Source: The New England Journal of Medicine. 2003 November 27; 349(22): 2164-7; Author Reply 2164-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14658126&dopt=Abstract
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Low-intensity versus conventional-intensity warfarin for prevention of recurrent venous thromboembolism. Author(s): Ridker PM, Goldhaber SZ, Glynn RJ. Source: The New England Journal of Medicine. 2003 November 27; 349(22): 2164-7; Author Reply 2164-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14658125&dopt=Abstract
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Low-intensity versus conventional-intensity warfarin for prevention of recurrent venous thromboembolism. Author(s): Brotman DJ. Source: The New England Journal of Medicine. 2003 November 27; 349(22): 2164-7; Author Reply 2164-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14658124&dopt=Abstract
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Low-intensity versus conventional-intensity warfarin for prevention of recurrent venous thromboembolism. Author(s): Huisman MV, van der Meer FJ, van Rooden CJ, Prins MH. Source: The New England Journal of Medicine. 2003 November 27; 349(22): 2164-7; Author Reply 2164-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14645647&dopt=Abstract
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Low-intensity warfarin therapy for the prevention of recurrent venous thromboembolism. Author(s): Seneviratne C, Kupfer Y, Tessler S. Source: The New England Journal of Medicine. 2003 July 24; 349(4): 398-400; Author Reply 398-400. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12879892&dopt=Abstract
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Low-intensity warfarin therapy for the prevention of recurrent venous thromboembolism. Author(s): Aberegg SK. Source: The New England Journal of Medicine. 2003 July 24; 349(4): 398-400; Author Reply 398-400. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12879891&dopt=Abstract
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Low-intensity warfarin therapy for the prevention of recurrent venous thromboembolism. Author(s): Cosmi B, Palareti G. Source: The New England Journal of Medicine. 2003 July 24; 349(4): 398-400; Author Reply 398-400. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12879889&dopt=Abstract
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Low-intensity warfarin therapy for the prevention of recurrent venous thromboembolism. Author(s): Krishnan JA, Streiff MB. Source: The New England Journal of Medicine. 2003 July 24; 349(4): 398-400; Author Reply 398-400. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12879888&dopt=Abstract
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Low-intensity warfarin therapy for the prevention of recurrent venous thromboembolism. Author(s): van Dongen CJ, Prins MH, Buller HR. Source: The New England Journal of Medicine. 2003 July 24; 349(4): 398-400; Author Reply 398-400. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12878749&dopt=Abstract
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Low-molecular-weight heparin (nadroparin) and very low doses of warfarin in the prevention of upper extremity thrombosis in cancer patients with indwelling longterm central venous catheters: a pilot randomized trial. Author(s): Mismetti P, Mille D, Laporte S, Charlet V, Buchmuller-Cordier A, Jacquin JP, Fournel P, Dutrey-Dupagne C, Decousus H; CIP Study Group. Source: Haematologica. 2003 January; 88(1): 67-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12551829&dopt=Abstract
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Major bleeding caused by warfarin in a genetically susceptible patient. Author(s): Bloch A, Ben-Chetrit E, Muszkat M, Caraco Y. Source: Pharmacotherapy. 2002 January; 22(1): 97-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11794436&dopt=Abstract
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Managing excessive warfarin anticoagulation. Author(s): Bussey HI. Source: Annals of Internal Medicine. 2001 September 18; 135(6): 460-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11560459&dopt=Abstract
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Managing patients on warfarin therapy: a case report. Author(s): Aldous JA, Olson CJ. Source: Spec Care Dentist. 2001 May-June; 21(3): 109-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11507845&dopt=Abstract
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Managing the warfarinized urological patient. Author(s): Meyer JP, Gillatt DA, Lush R, Persad R. Source: Bju International. 2003 September; 92(4): 351-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12930417&dopt=Abstract
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Massive subretinal bleed in a patient with background diabetic retinopathy and on treatment with warfarin. Author(s): Raj A, Sekhri R, Salam A, Priya P. Source: Eye (London, England). 2003 July; 17(5): 649-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12855977&dopt=Abstract
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Mechanism of binding of warfarin enantiomers to recombinant domains of human albumin. Author(s): Twine SM, Gore MG, Morton P, Fish BC, Lee AG, East JM. Source: Archives of Biochemistry and Biophysics. 2003 June 1; 414(1): 83-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12745258&dopt=Abstract
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Metformin-induced acidosis due to a warfarin adverse drug event. Author(s): Schier JG, Hoffman RS, Nelson LS. Source: The Annals of Pharmacotherapy. 2003 July-August; 37(7-8): 1145. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12841833&dopt=Abstract
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Miconazole-warfarin interaction: increased INR. Author(s): Murty M. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 2001 July 10; 165(1): 81-2, 85-6. English, French. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11468962&dopt=Abstract
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Minidose (1 mg) warfarin as prophylaxis for central vein catheter thrombosis. Author(s): Heaton DC, Han DY, Inder A. Source: Internal Medicine Journal. 2002 March; 32(3): 84-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11885848&dopt=Abstract
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Minidose warfarin prophylaxis for catheter-associated thrombosis in cancer patients: can it be safely associated with fluorouracil-based chemotherapy? Author(s): Masci G, Magagnoli M, Zucali PA, Castagna L, Carnaghi C, Sarina B, Pedicini V, Fallini M, Santoro A. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 February 15; 21(4): 736-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12586814&dopt=Abstract
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Mutations of the CYP2C9 gene and the response to warfarin. Author(s): Yasar U, Oscarson M, Eliasson E, Sjoqvist F. Source: Surgery. 2001 March; 129(3): 384. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11231472&dopt=Abstract
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Need for increased dose of warfarin in HIV patients taking nevirapine. Author(s): Dionisio D, Mininni S, Bartolozzi D, Esperti F, Vivarelli A, Leoncini F. Source: Aids (London, England). 2001 January 26; 15(2): 277-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11216940&dopt=Abstract
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No effect of the novel antidiabetic agent nateglinide on the pharmacokinetics and anticoagulant properties of warfarin in healthy volunteers. Author(s): Anderson DM, Shelley S, Crick N, Buraglio M. Source: Journal of Clinical Pharmacology. 2002 December; 42(12): 1358-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12463731&dopt=Abstract
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Optimal intensity of international normalized ratio in warfarin therapy for secondary prevention of stroke in patients with non-valvular atrial fibrillation. Author(s): Yasaka M, Minematsu K, Yamaguchi T. Source: Intern Med. 2001 December; 40(12): 1183-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11813841&dopt=Abstract
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Optimal intensity of warfarin therapy for secondary prevention of stroke in patients with nonvalvular atrial fibrillation : a multicenter, prospective, randomized trial. Japanese Nonvalvular Atrial Fibrillation-Embolism Secondary Prevention Cooperative Study Group. Author(s): Yamaguchi T. Source: Stroke; a Journal of Cerebral Circulation. 2000 April; 31(4): 817-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10753981&dopt=Abstract
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Oral vitamin K for warfarin-associated coagulopathy. Author(s): Weideman R, Patel AP. Source: Annals of Internal Medicine. 2003 April 1; 138(7): 610; Author Reply 611. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12667043&dopt=Abstract
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Oral vitamin K for warfarin-associated coagulopathy. Author(s): Ringstrom E, Long H. Source: Annals of Internal Medicine. 2003 April 1; 138(7): 610-1; Author Reply 611. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12667042&dopt=Abstract
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Oral vitamin K lowers the international normalized ratio more rapidly than subcutaneous vitamin K in the treatment of warfarin-associated coagulopathy. A randomized, controlled trial. Author(s): Crowther MA, Douketis JD, Schnurr T, Steidl L, Mera V, Ultori C, Venco A, Ageno W. Source: Annals of Internal Medicine. 2002 August 20; 137(4): 251-4. Summary for Patients In: http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12186515&dopt=Abstract
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Orlistat enhances warfarin effect. Author(s): MacWalter RS, Fraser HW, Armstrong KM. Source: The Annals of Pharmacotherapy. 2003 April; 37(4): 510-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12659605&dopt=Abstract
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Out of hospital antithrombotic prophylaxis after total hip replacement: lowmolecular-weight heparin, warfarin, aspirin or nothing? A cost-effectiveness analysis. Author(s): Sarasin FP, Bounameaux H. Source: Thrombosis and Haemostasis. 2002 April; 87(4): 586-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12008939&dopt=Abstract
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Patient-specific factors predictive of warfarin dosage requirements. Author(s): Absher RK, Moore ME, Parker MH. Source: The Annals of Pharmacotherapy. 2002 October; 36(10): 1512-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12243598&dopt=Abstract
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Pharmacokinetic and pharmacodynamic interactions between the novel calcium sensitiser levosimendan and warfarin. Author(s): Antila S, Jarvinen A, Honkanen T, Lehtonen L. Source: European Journal of Clinical Pharmacology. 2000 December; 56(9-10): 705-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11214780&dopt=Abstract
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Pharmacokinetic study of FFP photochemically treated with amotosalen (S-59) and UV light compared to FFP in healthy volunteers anticoagulated with warfarin. Author(s): Hambleton J, Wages D, Radu-Radulescu L, Adams M, MacKenzie M, Shafer S, Lee M, Smyers J, Wiesehahn G, Corash L. Source: Transfusion. 2002 October; 42(10): 1302-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12423514&dopt=Abstract
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Population differences in S-warfarin metabolism between CYP2C9 genotype-matched Caucasian and Japanese patients. Author(s): Takahashi H, Wilkinson GR, Caraco Y, Muszkat M, Kim RB, Kashima T, Kimura S, Echizen H. Source: Clinical Pharmacology and Therapeutics. 2003 March; 73(3): 253-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12621390&dopt=Abstract
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Possible effect of refrigeration of warfarin on the international normalized ratio. Author(s): Sharp RP, Havrda DE. Source: Pharmacotherapy. 2002 January; 22(1): 102-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11794419&dopt=Abstract
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Possible interaction between gatifloxacin and warfarin. Author(s): Artymowicz RJ, Cino BJ, Rossi JG, Walker JL, Moore S. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 2002 June 15; 59(12): 1205-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12073864&dopt=Abstract
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Possible interaction between warfarin and Lycium barbarum L. Author(s): Lam AY, Elmer GW, Mohutsky MA. Source: The Annals of Pharmacotherapy. 2001 October; 35(10): 1199-201. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11675844&dopt=Abstract
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Possible international normalized ratio elevation associated with celecoxib and warfarin in an elderly psychiatric patient. Author(s): Stoner SC, Lea JW, Dubisar BM, Farrar C. Source: Journal of the American Geriatrics Society. 2003 May; 51(5): 728-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12752860&dopt=Abstract
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Potential impact of therapeutic warfarin treatment on type II endoleaks and sac shrinkage rates on midterm follow-up examination. Author(s): Fairman RM, Carpenter JP, Baum RA, Larson RA, Golden MA, Barker CF, Mitchell ME, Velazquez OC. Source: Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. 2002 April; 35(4): 679-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11932662&dopt=Abstract
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Practical tips for warfarin dosing and monitoring. Author(s): Jaffer A, Bragg L. Source: Cleve Clin J Med. 2003 April; 70(4): 361-71. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12701992&dopt=Abstract
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Predictors of warfarin use among Ohio medicaid patients with new-onset nonvalvular atrial fibrillation. Author(s): Johnston JA, Cluxton RJ Jr, Heaton PC, Guo JJ, Moomaw CJ, Eckman MH. Source: Archives of Internal Medicine. 2003 July 28; 163(14): 1705-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12885686&dopt=Abstract
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Predisposing factors for enlargement of intracerebral hemorrhage in patients treated with warfarin. Author(s): Yasaka M, Minematsu K, Naritomi H, Sakata T, Yamaguchi T. Source: Thrombosis and Haemostasis. 2003 February; 89(2): 278-83. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12574807&dopt=Abstract
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Pregnancy outcome after maternal poisoning with brodifacoum, a long-acting warfarin-like rodenticide. Author(s): Zurawski JM, Kelly EA. Source: Obstetrics and Gynecology. 1997 October; 90(4 Pt 2): 672-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11770591&dopt=Abstract
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Preinjury warfarin does not impact outcome in trauma patients. Author(s): Wojcik R, Cipolle MD, Seislove E, Wasser TE, Pasquale MD. Source: The Journal of Trauma. 2001 December; 51(6): 1147-51; Discussion 1151-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11740267&dopt=Abstract
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Preoperative monitoring of warfarin in cutaneous surgery. Author(s): Ah-Weng A, Natarajan S, Velangi S, Langtry JA. Source: The British Journal of Dermatology. 2003 August; 149(2): 386-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12932248&dopt=Abstract
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Prevalence and quality of warfarin use for patients with atrial fibrillation in the longterm care setting. Author(s): McCormick D, Gurwitz JH, Goldberg RJ, Becker R, Tate JP, Elwell A, Radford MJ. Source: Archives of Internal Medicine. 2001 November 12; 161(20): 2458-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11700158&dopt=Abstract
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Prevalence of ocular hemorrhage in patients receiving warfarin therapy. Author(s): Superstein R, Gomolin JE, Hammouda W, Rosenberg A, Overbury O, Arsenault C. Source: Can J Ophthalmol. 2000 December; 35(7): 385-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11192447&dopt=Abstract
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Prevention of bleeding in older patients taking warfarin. Author(s): Kajubi S. Source: Annals of Internal Medicine. 2001 October 2; 135(7): 548-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11578160&dopt=Abstract
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Probing the structure of the warfarin-binding site on human serum albumin using site-directed mutagenesis. Author(s): Petersen CE, Ha CE, Curry S, Bhagavan NV. Source: Proteins. 2002 May 1; 47(2): 116-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11933059&dopt=Abstract
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Purple toes syndrome associated with warfarin therapy in a patient with antiphospholipid syndrome. Author(s): Talmadge DB, Spyropoulos AC. Source: Pharmacotherapy. 2003 May; 23(5): 674-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12741443&dopt=Abstract
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Quantitative liquid chromatography/mass spectrometry/mass spectrometry warfarin assay for in vitro cytochrome P450 studies. Author(s): Zhang ZY, King BM, Wong YN. Source: Analytical Biochemistry. 2001 November 1; 298(1): 40-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11673893&dopt=Abstract
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Racial background is a determinant factor in the maintenance dosage of warfarin. Author(s): Gan GG, Teh A, Goh KY, Chong HT, Pang KW. Source: International Journal of Hematology. 2003 July; 78(1): 84-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12894858&dopt=Abstract
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Rapid reversal of oral anticoagulation with warfarin by a prothrombin complex concentrate (Beriplex): efficacy and safety in 42 patients. Author(s): Preston FE, Laidlaw ST, Sampson B, Kitchen S. Source: British Journal of Haematology. 2002 March; 116(3): 619-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11849221&dopt=Abstract
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Re: Does PC-SPES interact with warfarin? Author(s): Duncan GG. Source: The Journal of Urology. 2003 January; 169(1): 294-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12478174&dopt=Abstract
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Re: Sugar A W et al. Can warfarin be continued during dental extraction? Results of a randomised controlled trial. Br J Oral Maxillofac Surg 2002; 40: 248-252. Author(s): Gibbons AJ, Sugar AW. Source: The British Journal of Oral & Maxillofacial Surgery. 2003 August; 41(4): 280. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12946679&dopt=Abstract
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Re: Sugar AW et al. Can warfarin be continued during dental extraction? Results of a randomised controlled trial. Br J Oral Maxillofac Surg 2002; 40: 248-252. Author(s): Sen P, Sen R. Source: The British Journal of Oral & Maxillofacial Surgery. 2003 April; 41(2): 132. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12694713&dopt=Abstract
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Recombinant coagulation factor VIIa for rapid preoperative correction of warfarinrelated coagulopathy in patients with acute subdural hematoma. Author(s): Veshchev I, Elran H, Salame K. Source: Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. 2002 December; 8(12): Cs98-100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12503044&dopt=Abstract
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Recommendations for the management of over-anticoagulation with warfarin. Author(s): Isbister GK, Dawson A, Isbister JP. Source: Emergency Medicine (Fremantle, W.A.). 2001 December; 13(4): 469-71; Discussion 471-2. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11903434&dopt=Abstract
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Reducing risks for patients receiving warfarin. Author(s): Bush J. Source: Family Practice Management. 2002 July-August; 9(7): 35-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12221762&dopt=Abstract
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Regarding postoperative stroke after warfarin for cutaneous surgery. Author(s): Goldman G. Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 2001 January; 27(1): 90-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11231258&dopt=Abstract
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Relationship between patients' warfarin knowledge and anticoagulation control. Author(s): Tang EO, Lai CS, Lee KK, Wong RS, Cheng G, Chan TY. Source: The Annals of Pharmacotherapy. 2003 January; 37(1): 34-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12503930&dopt=Abstract
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Reply to rebuttal: Gene variants of the cytochrome P450 CYP2C9 affect oral anticoagulation with warfarin. Author(s): Margaglione M, Brancaccio V, Ciampa A, Di Minno G. Source: Thrombosis and Haemostasis. 2001 September; 86(3): 938. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11583336&dopt=Abstract
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Results of an economic model to assess the cost-effectiveness of enoxaparin, a lowmolecular-weight heparin, versus warfarin for the prophylaxis of deep vein thrombosis and associated long-term complications in total hip replacement surgery in the United States. Author(s): Botteman MF, Caprini J, Stephens JM, Nadipelli V, Bell CF, Pashos CL, Cohen AT. Source: Clinical Therapeutics. 2002 November; 24(11): 1960-86; Discussion 1938. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12501885&dopt=Abstract
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Retroperitoneal haemorrhage during warfarin therapy. Author(s): Tang T, Lee J, Dickinson R. Source: Journal of the Royal Society of Medicine. 2003 June; 96(6): 294-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12782698&dopt=Abstract
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Reversal of warfarin-induced excessive anticoagulation with recombinant human factor VIIa concentrate. Author(s): Deveras RA, Kessler CM. Source: Annals of Internal Medicine. 2002 December 3; 137(11): 884-8. Summary for Patients In: http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12458988&dopt=Abstract
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Revisiting the significance of warfarin protein-binding displacement interactions. Author(s): Sands CD, Chan ES, Welty TE. Source: The Annals of Pharmacotherapy. 2002 October; 36(10): 1642-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12369572&dopt=Abstract
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Risk of ischemic stroke and hemorrhagic complications in warfarinized patients with non-valvular atrial fibrillation. Author(s): Uchiyama S. Source: Intern Med. 2001 December; 40(12): 1166-7. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11813834&dopt=Abstract
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Risk of warfarin during pregnancy with mechanical valve prostheses. Author(s): Regenstein A. Source: Obstetrics and Gynecology. 2002 November; 100(5 Pt 1): 1040-1; Discussion 141. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12423875&dopt=Abstract
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Risk of warfarin during pregnancy with mechanical valve prostheses. Author(s): Cotrufo M, De Feo M, De Santo LS, Romano G, Della Corte A, Renzulli A, Gallo C. Source: Obstetrics and Gynecology. 2002 January; 99(1): 35-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11777507&dopt=Abstract
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Risks and benefits of adding anti-platelet therapy to warfarin among patients with prosthetic heart valves: a meta-analysis. Author(s): Massel D, Little SH. Source: Journal of the American College of Cardiology. 2001 February; 37(2): 569-78. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11216981&dopt=Abstract
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Role of desethylamiodarone in the anticoagulant effect of concurrent amiodarone and warfarin therapy. Author(s): Naganuma M, Shiga T, Nishikata K, Tsuchiya T, Kasanuki H, Fujii E. Source: Journal of Cardiovascular Pharmacology and Therapeutics. 2001 October; 6(4): 363-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11907638&dopt=Abstract
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Safety and effectiveness of low dose oral vitamin K1 administration in asymptomatic out-patients on warfarin or acenocoumarol with excessive anticoagulation. Author(s): Poli D, Antonucci E, Lombardi A, Gensini GF, Abbate R, Prisco D. Source: Haematologica. 2003 February; 88(2): 237-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12604423&dopt=Abstract
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Safety of a clinical surveillance protocol with 3- and 6-week warfarin prophylaxis after total joint arthroplasty. Author(s): Goldstein WM, Jimenez ML, Bailie DS, Wall R, Branson J. Source: Orthopedics. 2001 July; 24(7): 651-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11478551&dopt=Abstract
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Seasonal control of warfarin therapy. Author(s): Gage BF, Fihn SD, White RH. Source: The American Journal of Medicine. 2001 September; 111(4): 332. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11583017&dopt=Abstract
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Seaweed, vitamin K, and warfarin. Author(s): Bartle WR, Madorin P, Ferland G. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 2001 December 1; 58(23): 2300. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11763808&dopt=Abstract
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Secondary prophylaxis with warfarin for venous thromboembolism. Author(s): Buller HR, Prins MH. Source: The New England Journal of Medicine. 2003 August 14; 349(7): 702-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12917308&dopt=Abstract
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Sevelamer hydrochloride (Renagel), a nonabsorbed phosphate-binding polymer, does not interfere with digoxin or warfarin pharmacokinetics. Author(s): Burke S, Amin N, Incerti C, Plone M, Watson N. Source: Journal of Clinical Pharmacology. 2001 February; 41(2): 193-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11210401&dopt=Abstract
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Seven cases of interaction between warfarin and cyclooxygenase-2 inhibitors. Author(s): Stading JA, Skrabal MZ, Faulkner MA. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 2001 November 1; 58(21): 2076-80. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11715832&dopt=Abstract
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Species comparison of vitamin K1 2,3-epoxide reductase activity in vitro: kinetics and warfarin inhibition. Author(s): Wilson CR, Sauer JM, Carlson GP, Wallin R, Ward MP, Hooser SB. Source: Toxicology. 2003 August 1; 189(3): 191-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12832152&dopt=Abstract
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Specific clinical constellations might mask the genetic over-sensitivity to warfarin. Author(s): Kurnik D, Loebstein R, Halkin H. Source: Isr Med Assoc J. 2002 June; 4(6): 475; Author Reply 475-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12073434&dopt=Abstract
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Spinal epidural haematoma as a result of warfarin/fluconazole drug interaction. Author(s): Allison EJ Jr, McKinney TJ, Langenberg JN. Source: European Journal of Emergency Medicine : Official Journal of the European Society for Emergency Medicine. 2002 June; 9(2): 175-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12131644&dopt=Abstract
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Spontaneous supraglottic haemorrhage in a patient receiving warfarin sodium treatment. Author(s): Uppal HS, Ayshford CA, Syed MA. Source: Emergency Medicine Journal : Emj. 2001 September; 18(5): 406-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11559624&dopt=Abstract
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Starting warfarin as an outpatient. Author(s): Channer KS. Source: The British Journal of General Practice : the Journal of the Royal College of General Practitioners. 2002 March; 52(476): 238-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12030679&dopt=Abstract
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Steady-state pharmacodynamics and pharmacokinetics of warfarin in the presence and absence of telmisartan in healthy male volunteers. Author(s): Stangier J, Su CA, Hendriks MG, van Lier JJ, Sollie FA, Oosterhuis B, Jonkman JH. Source: Journal of Clinical Pharmacology. 2000 December; 40(12 Pt 1): 1331-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11185631&dopt=Abstract
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Stereoselective kinetics of warfarin binding to human serum albumin: effect of an allosteric interaction. Author(s): Fitos I, Visy J, Kardos J. Source: Chirality. 2002 May 15; 14(5): 442-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11984760&dopt=Abstract
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Studies on coumarin anticoagulant drugs. Initiation of warfarin therapy without a loading dose. Author(s): O'Reilly RA, Aggeler PM. Source: Circulation. 1968 July; 38(1): 169-77. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11712286&dopt=Abstract
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Substitution of generic warfarin for Coumadin in an HMO setting. Author(s): Milligan PE, Banet GA, Waterman AD, Gatchel SK, Gage BF. Source: The Annals of Pharmacotherapy. 2002 May; 36(5): 764-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11978149&dopt=Abstract
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Subtherapeutic INR values associated with a switch to generic warfarin. Author(s): Hope KA, Havrda DE. Source: The Annals of Pharmacotherapy. 2001 February; 35(2): 183-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11215837&dopt=Abstract
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Superior venocaval obstruction secondary to central venous catheter-related thromboses in two patients with metastatic colorectal carcinoma receiving weekly 5flurouracil. Should adjusted-dose warfarin be used as thromboprophylaxis? Author(s): Mainwaring CJ, Naylor E, Jerwood S, Hall V, Page A, James CM. Source: Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis. 2002 December; 13(8): 749-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12441915&dopt=Abstract
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Superwarfarin poisoning--a report of 4 cases. Author(s): Poovalingam V, Kenoyer DG, Mahomed R, Rapiti N, Bassa F, Govender P. Source: South African Medical Journal. Suid-Afrikaanse Tydskrif Vir Geneeskunde. 2002 November; 92(11): 874-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12506584&dopt=Abstract
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Suprachoroidal haemorrhage after addition of clarithromycin to warfarin. Author(s): Dandekar SS, Laidlaw DA. Source: Journal of the Royal Society of Medicine. 2001 November; 94(11): 583-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11691898&dopt=Abstract
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The effects of aspirin and warfarin therapy on haemorrhage in vitreoretinal surgery. Author(s): Narendran N, Williamson TH. Source: Acta Ophthalmologica Scandinavica. 2003 February; 81(1): 38-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12631017&dopt=Abstract
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The frequency and effects of cytochrome P450 (CYP) 2C9 polymorphisms in patients receiving warfarin. Author(s): Tabrizi AR, Zehnbauer BA, Borecki IB, McGrath SD, Buchman TG, Freeman BD. Source: Journal of the American College of Surgeons. 2002 March; 194(3): 267-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11893129&dopt=Abstract
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The great warfarin debate. Author(s): Malden N. Source: British Dental Journal. 2003 July 12; 195(1): 2-3; Author Reply 3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12856004&dopt=Abstract
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The incidence of bleeding complications associated with warfarin treatment in general practice in the United Kingdom. Author(s): Hollowell J, Ruigomez A, Johansson S, Wallander MA, Garcia-Rodriguez LA. Source: The British Journal of General Practice : the Journal of the Royal College of General Practitioners. 2003 April; 53(489): 312-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12879832&dopt=Abstract
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The nature and frequency of potential warfarin drug interactions that increase the risk of bleeding in patients with atrial fibrillation. Author(s): Howard PA, Ellerbeck EF, Engelman KK, Patterson KL. Source: Pharmacoepidemiology and Drug Safety. 2002 October-November; 11(7): 569-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12462133&dopt=Abstract
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The perioperative management of warfarin therapy. Author(s): Ansell JE. Source: Archives of Internal Medicine. 2003 April 28; 163(8): 881-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12719195&dopt=Abstract
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The relative importance of barriers to the prescription of warfarin for nonvalvular atrial fibrillation. Author(s): Bungard TJ, Ghali WA, McAlister FA, Buchan AM, Cave AJ, Hamilton PG, Mitchell LB, Shuaib A, Teo KK, Tsuyuki RT. Source: The Canadian Journal of Cardiology. 2003 March 15; 19(3): 280-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12677283&dopt=Abstract
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The risk of fetal loss associated with Warfarin anticoagulation. Author(s): Blickstein D, Blickstein I. Source: International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics. 2002 September; 78(3): 221-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12384267&dopt=Abstract
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The synthetic pentasaccharide fondaparinux sodium does not interact with oral warfarin. Author(s): Faaij RA, Burggraaf J, Schoemaker RC, de Greef R, Cohen AF. Source: Clinical Pharmacokinetics. 2002; 41 Suppl 2: 27-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12383042&dopt=Abstract
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The use of oral anticoagulants (warfarin) in older people. American Geriatrics Society guideline. Author(s): American Geriatrics Society Clinical Practice Committee. Source: Journal of the American Geriatrics Society. 2002 August; 50(8): 1439-45; Discussion 1446-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12165003&dopt=Abstract
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The use of oral vitamin K for reversal of over-warfarinization. Author(s): Watson HG, Baglin TP, Makris M. Source: British Journal of Haematology. 2002 January; 116(1): 237. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11848091&dopt=Abstract
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The use of recombinant activated factor VII to reverse warfarin-induced anticoagulation in patients with hemorrhages in the central nervous system: preliminary findings. Author(s): Lin J, Hanigan WC, Tarantino M, Wang J. Source: Journal of Neurosurgery. 2003 April; 98(4): 737-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12691397&dopt=Abstract
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The use of vitamin K for reversal of over-warfarinization in children. Author(s): Bolton-Maggs P, Brook L. Source: British Journal of Haematology. 2002 September; 118(3): 924. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12181071&dopt=Abstract
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Therapeutic monitoring of warfarin: the appropriate response marker. Author(s): Costa IM, Soares PJ, Afonso M, Ratado P, Lanaot JM, Falcao AC. Source: The Journal of Pharmacy and Pharmacology. 2000 November; 52(11): 1405-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11186249&dopt=Abstract
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Thrombosis of a prosthetic aortic valve disclosing a hazardous interaction between warfarin and a commercial ginseng product. Author(s): Rosado MF. Source: Cardiology. 2003; 99(2): 111. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12711887&dopt=Abstract
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Thrombosis prevention trial: compliance with warfarin treatment and investigation of a retained effect. Author(s): Rudnicka AR, Ashby D, Brennan P, Meade T. Source: Archives of Internal Medicine. 2003 June 23; 163(12): 1454-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12824095&dopt=Abstract
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Thrombotic complications related to discontinuation of warfarin and aspirin therapy perioperatively for cutaneous operation. Author(s): Kovich O, Otley CC. Source: Journal of the American Academy of Dermatology. 2003 February; 48(2): 233-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12582394&dopt=Abstract
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Time course and frequency of subtherapeutic anticoagulation for newly prescribed warfarin anticoagulation before elective cardioversion of atrial fibrillation or flutter. Author(s): Kim MH, Krishnan K, Jain S, Decena BF. Source: The American Journal of Cardiology. 2001 December 15; 88(12): 1428-31, A8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11741568&dopt=Abstract
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Toward safer warfarin therapy: does precise daily dosing improve international normalized ratio control? Author(s): Manning DM. Source: Mayo Clinic Proceedings. 2002 August; 77(8): 873-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12173723&dopt=Abstract
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Treatment of warfarin-associated coagulopathy: a physician survey. Author(s): Wilson SE, Douketis JD, Crowther MA. Source: Chest. 2001 December; 120(6): 1972-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11742930&dopt=Abstract
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Unusual liver damage ensuing after warfarin administration in a pregnant woman with caval thrombosis. Author(s): Amitrano L, Guardascione MA, Balzano A, Brancaccio V, Iannaccone L, Ames PR. Source: Dig Liver Dis. 2003 January; 35(1): 61-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12725611&dopt=Abstract
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Urinary retention and intravesical hemorrhage following urethral collagen injections in women using warfarin. Author(s): Theofrastous JP, Simpkins K. Source: International Urogynecology Journal and Pelvic Floor Dysfunction. 2002; 13(4): 268-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12189435&dopt=Abstract
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Use of herbal medicines by patients receiving warfarin. Author(s): Wong RS, Cheng G, Chan TY. Source: Drug Safety : an International Journal of Medical Toxicology and Drug Experience. 2003; 26(8): 585-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12825970&dopt=Abstract
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Use of warfarin during pregnancy. Author(s): Abadi S, Einarson A, Koren G. Source: Can Fam Physician. 2002 April; 48: 695-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12046363&dopt=Abstract
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Variations of prothrombin time and international normalized ratio in patients treated with warfarin. Author(s): Ho CH, Lin MW, You JY, Chen CC, Yu TJ. Source: Thrombosis Research. 2002 September 1; 107(5): 277-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12479890&dopt=Abstract
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Venous limb gangrene during overlapping therapy with warfarin and a direct thrombin inhibitor for immune heparin-induced thrombocytopenia. Author(s): Smythe MA, Warkentin TE, Stephens JL, Zakalik D, Mattson JC. Source: American Journal of Hematology. 2002 September; 71(1): 50-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12221676&dopt=Abstract
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Venous limb gangrene during warfarin treatment of cancer-associated deep venous thrombosis. Author(s): Warkentin TE. Source: Annals of Internal Medicine. 2001 October 16; 135(8 Pt 1): 589-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11601930&dopt=Abstract
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Very low dose warfarin as prophylaxis against ultrasound detected deep vein thrombosis following primary hip replacement. Author(s): Bern MM, Bierbaum B, Wetzner S, Brennan W, McAlister S. Source: American Journal of Hematology. 2002 October; 71(2): 69-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12353302&dopt=Abstract
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Visual complications of warfarin. Author(s): Kowal LM, Harper CA. Source: The Medical Journal of Australia. 2002 April 1; 176(7): 351. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12013331&dopt=Abstract
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Vitamin K for warfarin-associated coagulopathy. Author(s): Witt MD, Patel R, Tillman DJ, Wilkinson DS. Source: Lancet. 2001 March 3; 357(9257): 718. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11247582&dopt=Abstract
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Warfarin and amoxicillin/clavulanate drug interaction. Author(s): Davydov L, Yermolnik M, Cuni LJ. Source: The Annals of Pharmacotherapy. 2003 March; 37(3): 367-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12639164&dopt=Abstract
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Warfarin and aspirin give more benefit than aspirin alone but also more bleeding after myocardial infarction. Author(s): Doggrell SA. Source: Expert Opinion on Pharmacotherapy. 2003 April; 4(4): 587-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12667121&dopt=Abstract
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Warfarin and extraction. Author(s): Balderston RH. Source: British Dental Journal. 2003 April 26; 194(8): 408-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12778085&dopt=Abstract
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Warfarin and extractions. Author(s): Malden NJ. Source: British Dental Journal. 2003 January 25; 194(2): 65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12596738&dopt=Abstract
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Warfarin and extractions. Author(s): Brown AE. Source: British Dental Journal. 2002 December 21; 193(12): 668. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12536981&dopt=Abstract
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Warfarin dose adjustments based on CYP2C9 genetic polymorphisms. Author(s): Linder MW, Looney S, Adams JE 3rd, Johnson N, Antonino-Green D, Lacefield N, Bukaveckas BL, Valdes R Jr. Source: Journal of Thrombosis and Thrombolysis. 2002 December; 14(3): 227-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12913403&dopt=Abstract
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Warfarin dose reduction vs watchful waiting for mild elevations in the international normalized ratio. Author(s): Banet GA, Waterman AD, Milligan PE, Gatchel SK, Gage BF. Source: Chest. 2003 February; 123(2): 499-503. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12576372&dopt=Abstract
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Warfarin for non-valvar atrial fibrillation: still underused in the 21st century? Author(s): Bo S, Ciccone G, Scaglione L, Taliano C, Piobbici M, Merletti F, Pagano G. Source: Heart (British Cardiac Society). 2003 May; 89(5): 553-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12695466&dopt=Abstract
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Warfarin for venous thromboembolism - walking the dosing tightrope. Author(s): Schafer AI. Source: The New England Journal of Medicine. 2003 April 10; 348(15): 1478-80. Epub 2003 February 24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12601074&dopt=Abstract
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Warfarin sensitivity: be aware of genetic influence. Author(s): Khan T, Kamali F, Daly A, King B, Wynne HA. Source: Age and Ageing. 2003 March; 32(2): 226-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12615570&dopt=Abstract
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Warfarin therapy and cataract surgery. Author(s): Morris A, Elder MJ. Source: Clinical & Experimental Ophthalmology. 2000 December; 28(6): 419-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11202464&dopt=Abstract
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Warfarin therapy in children who require long-term total parenteral nutrition. Author(s): Newall F, Barnes C, Savoia H, Campbell J, Monagle P. Source: Pediatrics. 2003 November; 112(5): E386. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14595081&dopt=Abstract
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Warfarin toxicity. A case study. Author(s): Nadeau C, Hudson L, Tari J, Coyne M, Ahern K, McGinn R. Source: Adv Nurse Pract. 2003 April; 11(4): 60-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12718107&dopt=Abstract
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Warfarin use in atrial fibrillation: A random sample survey of family physician beliefs and preferences. Author(s): Pradhan AA, Levine MA. Source: Can J Clin Pharmacol. 2002 Winter; 9(4): 199-202. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12584578&dopt=Abstract
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Warfarin, aspirin, or both after myocardial infarction. Author(s): Amit G, Ilia R, Zahger D. Source: The New England Journal of Medicine. 2003 January 16; 348(3): 256-7; Author Reply 256-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12530435&dopt=Abstract
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Warfarin, aspirin, or both after myocardial infarction. Author(s): Aronow WS. Source: The New England Journal of Medicine. 2003 January 16; 348(3): 256-7; Author Reply 256-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12530434&dopt=Abstract
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Warfarin-associated hypoprothrombinemia: an unusual presentation. Author(s): Williams D, Ponte CD. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 2003 February 1; 60(3): 274-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12613238&dopt=Abstract
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Warfarin-induced skin necrosis associated with acquired protein C deficiency. Author(s): Parsi K, Younger I, Gallo J. Source: The Australasian Journal of Dermatology. 2003 February; 44(1): 57-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12581084&dopt=Abstract
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Warfarin-induced tracheobronchial calcification. Author(s): Thoongsuwan N, Stern EJ. Source: Journal of Thoracic Imaging. 2003 April; 18(2): 110-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12700488&dopt=Abstract
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Wars on warfarin. Author(s): Randall CJ. Source: British Dental Journal. 2002 December 7; 193(11): 608. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12607613&dopt=Abstract
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Ximelagatran compared with warfarin for prevention of thromboembolism in patients with nonvalvular atrial fibrillation: Rationale, objectives, and design of a pair of clinical studies and baseline patient characteristics (SPORTIF III and V). Author(s): Halperin JL; Executive Steering Committee, SPORTIF III and V Study Investigators. Source: American Heart Journal. 2003 September; 146(3): 431-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12947359&dopt=Abstract
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Ximelagatran versus warfarin for stroke prevention in patients with nonvalvular atrial fibrillation. SPORTIF II: a dose-guiding, tolerability, and safety study. Author(s): Petersen P, Grind M, Adler J; SPORTIF II Investigators. Source: Journal of the American College of Cardiology. 2003 May 7; 41(9): 1445-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12742279&dopt=Abstract
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CHAPTER 2. NUTRITION AND WARFARIN Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and warfarin.
Finding Nutrition Studies on Warfarin 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 “warfarin” (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 warfarin: •
By the way, doctor. Drugs for atrial fibrillation. I had atrial fibrillation and was zapped back into sinus rhythm several weeks ago. It seems like I'm going to have to take either aspirin or Coumadin. Which is better, and why? Source: Lee, T H Harv-Health-Lett. 2001 April; 26(6): 8 1052-1577
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I have heard that eating green or leafy vegetables can be a problem when a person is taking the blood thinner Coumadin. Is this true? Author(s): Harvard Medical School, USA. Source: Lilly, L S Health-News. 2000 August; 6(8): 10 1081-5880
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Vitamin E and blood thinners. You advised readers not to take extra vitamin E if they were taking aspirin or Coumadin. Why? Source: Anonymous Johns-Hopkins-Med-Lett-Health-After-50. 1999 October; 11(8): 8 1042-1882
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Warfarin use and fracture risk. Author(s): USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111, USA. Source: Booth, S L Mayer, J Nutr-Revolume 2000 January; 58(1): 20-2 0029-6643
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Warfarin, aspirin, and atrial fibrillation. Source: Anonymous Harv-Heart-Lett. 1998 August; 8(12): 4-6 1051-5313
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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 “warfarin” (or a synonym): •
A comparison of heparin/warfarin and enoxaparin thromboprophylaxis in spinal cord injury: the Sheffield experience. Author(s): Princess Royal Spinal Injuries Unit, Northern General Hospital, Herries Road, Sheffield, S5 7AU, UK. Source: Thumbikat, P Poonnoose, P M Balasubrahmaniam, P Ravichandran, G McClelland, M R Spinal-Cord. 2002 August; 40(8): 416-20 1362-4393
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Anticoagulation with warfarin. A review of monitoring issues. Author(s): Kaiser Permanente, Aurora, Colo., USA. Source: Vogel, E Adv-Nurse-Pract. 2001 January; 9(1): 75-8, 81, 94 1096-6293
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Can warfarin be continued during dental extraction? Results of a randomized controlled trial. Author(s): Maxillofacial Unit, Morriston Hospital, Swansea, UK. Source: Evans, I L Sayers, M S Gibbons, A J Price, G Snooks, H Sugar, A W Br-J-OralMaxillofac-Surg. 2002 June; 40(3): 248-52 0266-4356
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Comparison of a nomogram and physician-adjusted dosage of warfarin for prophylaxis against deep-vein thrombosis after arthroplasty. Author(s): Department of Medicine, Division of Hematology, Dalhousie University, Queen Elizabeth II Health Sciences Centre, Room 432, Bethune, 1172 Tower Road, Halifax, Nova Scotia B3H 1V8, Canada.
[email protected] Source: Anderson, D R Wilson, S J Blundell, J Petrie, D Leighton, R Stanish, W Alexander, D Robinson, K S Burton, E Gross, M J-Bone-Joint-Surg-Am. 2002 November; 84-A(11): 1992-7 0021-9355
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Developmental expression of vitamin K-dependent gamma-carboxylase activity in zebrafish embryos: effect of warfarin. Author(s): Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229, USA. Source: Hanumanthaiah, R Thankavel, B Day, K Gregory, M Jagadeeswaran, P BloodCells-Mol-Dis. 2001 Nov-December; 27(6): 992-9 1079-9796
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Heparin and coumadin versus acetylsalicylic acid for prevention of restenosis after coronary angioplasty. Author(s): Swiss Cardiovascular Center, University Hospital, Bern, Switzerland. Source: Garachemani, Ali Reza Fleisch, Martin Windecker, Stephan Pfiffner, Dorothy Meier, Bernhard Catheter-Cardiovasc-Intervolume 2002 Mar; 55(3): 315-20 1522-1946
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Interactions of warfarin. Author(s): Clinical Department of R&D, IVAX-CR a. s., Ostravska 29, 747 70 Opava 9, Czech Republic. Source: Rehulkova, O Biomed-Pap-Med-Fac-Univ-Palacky-Olomouc-Czech-Repub. 2001 December; 145(2): 27-38 1213-8118
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Late-onset warfarin necrosis. Author(s): Department of Medicine (Dermatology), The University of Melbourne, St Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia. Source: Scarff, C E Baker, C Hill, P Foley, P Australas-J-Dermatol. 2002 August; 43(3): 202-6 0004-8380
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Low molecular weight heparin and warfarin in the treatment of patients with antiphospholipid syndrome during pregnancy. Author(s): Department of Medicine E, Sheba Medical Center, Sackler School of Medicine and School of Engineering, Tel-Aviv University, Israel.
[email protected] Source: Pauzner, R Dulitzki, M Langevitz, P Livneh, A Kenett, R Many, A ThrombHaemost. 2001 December; 86(6): 1379-84 0340-6245
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Minidose (1 mg) warfarin as prophylaxis for central vein catheter thrombosis. Author(s): Department of Haematology, Christchurch Hospital, University of Otago, New Zealand. Source: Heaton, D C Han, D Y Inder, A Intern-Med-J. 2002 March; 32(3): 84-8 1444-0903
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OH: nurses fail to follow orders re Coumadin: complications follow--patient's death results. Source: Anonymous Nurs-Law-Regan-Repage 2001 August; 42(3): 3 1528-848X
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Pharmacokinetic study of FFP photochemically treated with amotosalen (S-59) and UV light compared to FFP in healthy volunteers anticoagulated with warfarin. Author(s): Department of Medicine, General Clinical Research Center, Moffitt Hospital, University of California-San Francisco, San Francisco, CA, USA. Source: Hambleton, J Wages, D Radu Radulescu, L Adams, M MacKenzie, M Shafer, S Lee, M Smyers, J Wiesehahn, G Corash, L Transfusion. 2002 October; 42(10): 1302-7 0041-1132
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Recommendations for the management of over-anticoagulation with warfarin. Author(s): Department of Clinical Toxicology and Pharmacology, Newcastle Mater Hospital, Discipline of Clinical Pharmacology, University of Newcastle, Newcastle, Australia.
[email protected] Source: Isbister, G K Dawson, A Isbister, J P Emerg-Med-(Fremantle). 2001 December; 13(4): 469-71; discussion 471-2 1441-0737
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Reducing risks for patients receiving warfarin. Source: Bush, J Fam-Pract-Manag. 2002 Jul-August; 9(7): 35-8 1069-5648
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Role of desethylamiodarone in the anticoagulant effect of concurrent amiodarone and warfarin therapy. Author(s): Department of Pharmacy, The Heart Institute of Japan, Tokyo Women's Medical University, Tokyo, Japan. Source: Naganuma, M Shiga, T Nishikata, K Tsuchiya, T Kasanuki, H Fujii, E JCardiovasc-Pharmacol-Ther. 2001 October; 6(4): 363-7 1074-2484
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Spinal epidural haematoma as a result of warfarin/fluconazole drug interaction. Author(s): Department of Emergency Medicine, SUNY Upstate Medical University, Syracuse, New York, USA. Source: Allison, E J Jr McKinney, T J Langenberg, J N Eur-J-Emerg-Med. 2002 June; 9(2): 175-7 0969-9546
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Stereoselective kinetics of warfarin binding to human serum albumin: effect of an allosteric interaction. Author(s): Department of Molecular Pharmacology, Institute of Chemistry, Chemical Research Center, Hungarian Academy of Sciences, Budapest, Hungary.
[email protected] Source: Fitos, Ilona Visy, Julia Kardos, Julianna Chirality. 2002 May 15; 14(5): 442-8 08990042
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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
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Urinary retention and intravesical hemorrhage following urethral collagen injections in women using warfarin. Author(s): Mountain Area Health Education Center, Department of Obstetrics and Gynecology, Asheville, North Carolina 28801, USA.
[email protected] Source: Theofrastous, J P Simpkins, K Int-Urogynecol-J-Pelvic-Floor-Dysfunct. 2002; 13(4): 268-9 0937-3462
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Warfarin dosage in postpartum women: a case-control study. Author(s): Department of Fetomaternal Medicine, School of Human Development, University Hospital, Queen's Medical Centre, Nottingham, UK. Source: Brooks, Cath Rutherford, Jane M Gould, Jane Ramsay, Margaret M James, David K BJOG. 2002 February; 109(2): 187-90 1470-0328
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Warfarin prophylaxis for orthopaedic venous thromboembolic disease. Author(s): Department of Orthopaedics, University of Maryland School of Medicine, Baltimore, Maryland, USA. Source: Pellegrini, V D Jr Instr-Course-Lect. 2002; 51: 491-8 0065-6895
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Warfarin, aspirin, or both after myocardial infarction. Author(s): Department of Cardiology, Ulleval University Hospital, Oslo, Norway. Source: Hurlen, M Abdelnoor, M Smith, P Erikssen, J Arnesen, H N-Engl-J-Med. 2002 September 26; 347(13): 969-74 1533-4406
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Warfarin-Aspirin Recurrent Stroke Study (WARSS) trial: is warfarin really a reasonable therapeutic alternative to aspirin for preventing recurrent noncardioembolic ischemic stroke? Author(s): Department of Neurology, Royal Perth Hospital, Perth, Western Australia.
[email protected] Source: Hankey, Graeme J Stroke. 2002 June; 33(6): 1723-6 1524-4628
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
The following is a specific Web list relating to warfarin; 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 Alternative names: Vitamin C (Ascorbic Acid) Source: Integrative Medicine Communications; www.drkoop.com Vitamin C Source: Healthnotes, Inc.; www.healthnotes.com Vitamin C Source: Prima Communications, Inc.www.personalhealthzone.com Vitamin C (Ascorbic Acid) Alternative names: Ascorbic Acid Source: Integrative Medicine Communications; www.drkoop.com Vitamin D Source: Healthnotes, Inc.; www.healthnotes.com Vitamin E Source: Healthnotes, Inc.; www.healthnotes.com Vitamin E Alternative names: Alpha-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 Source: Healthnotes, Inc.; www.healthnotes.com Vitamin K Alternative names: Menadione Source: Integrative Medicine Communications; www.drkoop.com Vitamin K Source: Prima Communications, Inc.www.personalhealthzone.com
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Vitamin K Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10068,00.html •
Minerals Alpha-tocopherol Alternative names: Vitamin E Source: Integrative Medicine Communications; www.drkoop.com Beta-tocopherol Alternative names: Vitamin E 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 Chondroitin Alternative names: chondroitin sulfate, sodium chondroitin sulfate Source: Integrative Medicine Communications; www.drkoop.com D-alpha-tocopherol Alternative names: Vitamin E Source: Integrative Medicine Communications; www.drkoop.com Delta-tocopherol Alternative names: Vitamin E Source: Integrative Medicine Communications; www.drkoop.com Gamma-tocopherol Alternative names: Vitamin E Source: Integrative Medicine Communications; www.drkoop.com Iron Source: Healthnotes, Inc.; www.healthnotes.com Magnesium Source: Healthnotes, Inc.; www.healthnotes.com Vinpocetine Source: Prima Communications, Inc.www.personalhealthzone.com Zinc Source: Healthnotes, Inc.; www.healthnotes.com
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Food and Diet Broccoli Source: Healthnotes, Inc.; www.healthnotes.com Bruising Source: Healthnotes, Inc.; www.healthnotes.com Brussels Sprouts Source: Healthnotes, Inc.; www.healthnotes.com Cabbage Source: Healthnotes, Inc.; www.healthnotes.com Chives Source: Healthnotes, Inc.; www.healthnotes.com Collards Source: Healthnotes, Inc.; www.healthnotes.com Endive Source: Healthnotes, Inc.; www.healthnotes.com Garlic 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 Iceberg Lettuce Source: Healthnotes, Inc.; www.healthnotes.com Kale Source: Healthnotes, Inc.; www.healthnotes.com Omega-3 Fatty Acids Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,992,00.html Scallions Source: Healthnotes, Inc.; www.healthnotes.com Soy Source: Healthnotes, Inc.; www.healthnotes.com Spinach Source: Healthnotes, Inc.; www.healthnotes.com
Nutrition
Turnips Source: Healthnotes, Inc.; www.healthnotes.com
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CHAPTER 3. ALTERNATIVE MEDICINE AND WARFARIN Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to warfarin. At the conclusion of this chapter, we will provide additional sources.
National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov/) has created a link to the National Library of Medicine’s databases to facilitate research for articles that specifically relate to warfarin 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 “warfarin” (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 warfarin: •
“Resistance” to warfarin due to unrecognized vitamin K supplementation. Author(s): O'Reilly RA, Rytand DA. Source: The New England Journal of Medicine. 1980 July 17; 303(3): 160-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7383081&dopt=Abstract
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A prospective randomized trial of aspirin-clopidogrel combination therapy and doseadjusted warfarin on indices of thrombogenesis and platelet activation in atrial fibrillation. Author(s): Kamath S, Blann AD, Chin BS, Lip GY. Source: Journal of the American College of Cardiology. 2002 August 7; 40(3): 484-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12142115&dopt=Abstract
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A randomized trial of anticoagulation with warfarin and of alternating chemotherapy in extensive small-cell lung cancer by the Cancer and Leukemia Group B.
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Author(s): Chahinian AP, Propert KJ, Ware JH, Zimmer B, Perry MC, Hirsh V, Skarin A, Kopel S, Holland JF, Comis RL, et al. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 1989 August; 7(8): 993-1002. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2547030&dopt=Abstract •
Accidental poisoning by warfarin-contaminated herbal tea. Author(s): Norcross WA, Ganiats TG, Ralph LP, Seidel RG, Ikeda TS. Source: The Western Journal of Medicine. 1993 July; 159(1): 80-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8351917&dopt=Abstract
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Action of dipyridamole and warfarin on growth of human endothelial cells cultured in serum-free media. Author(s): Liem LK, Choong LH, Woo KT. Source: Clinical Biochemistry. 2001 March; 34(2): 141-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11311224&dopt=Abstract
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An adverse interaction between warfarin and 5-fluorouracil: A case report and review of the literature. Author(s): Brown MC. Source: Chemotherapy. 1999 September-October; 45(5): 392-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10473927&dopt=Abstract
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Anaesthesia for caesarean section in a patient with myotonic dystrophy receiving warfarin therapy. Author(s): Campbell AM, Thompson N. Source: Canadian Journal of Anaesthesia = Journal Canadien D'anesthesie. 1995 May; 42(5 Pt 1): 409-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7614649&dopt=Abstract
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Bosentan and warfarin interaction. Author(s): Murphey LM, Hood EH. Source: The Annals of Pharmacotherapy. 2003 July-August; 37(7-8): 1028-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12841813&dopt=Abstract
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Changes in the metabolic profiles of R- and S-warfarin and R- and S-phenprocoumon as a probe to categorize the effect of inducing agents on microsomal hydroxylases. Author(s): Porter WR, Wheeler C, Trager WF. Source: Biochemical Pharmacology. 1981 November 15; 30(22): 3099-104. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7337727&dopt=Abstract
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Chinese herbs and warfarin potentiation by 'danshen'. Author(s): Yu CM, Chan JC, Sanderson JE.
Alternative Medicine 99
Source: Journal of Internal Medicine. 1997 April; 241(4): 337-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9159606&dopt=Abstract •
Composition of cytochrome P-450 isozymes from hepatic microsomes of C57BL/6 and DBA/2 mice assessed by warfarin metabolism, immunoinhibition, and immunoelectrophoresis with anti-(rat cytochrome P-450). Author(s): Kaminsky LS, Dannan GA, Guengerich FP. Source: European Journal of Biochemistry / Febs. 1984 May 15; 141(1): 141-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6723656&dopt=Abstract
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Cyclophosphamide, prednisone, staphage lysate and warfarin in disseminated breast cancer. Author(s): D'Souza DP, Daly L, Thornes RD. Source: Ir Med J. 1980 October; 73(10): 385-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7429789&dopt=Abstract
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Danggui (Angelica sinensis) affects the pharmacodynamics but not the pharmacokinetics of warfarin in rabbits. Author(s): Lo AC, Chan K, Yeung JH, Woo KS. Source: Eur J Drug Metab Pharmacokinet. 1995 January-March; 20(1): 55-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7588995&dopt=Abstract
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Development and validation of a sensitive and robust LC-tandem MS method for the analysis of warfarin enantiomers in human plasma. Author(s): Naidong W, Ring PR, Midtlien C, Jiang X. Source: Journal of Pharmaceutical and Biomedical Analysis. 2001 May; 25(2): 219-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11275431&dopt=Abstract
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Does PC-SPEs interact with warfarin? Author(s): Davis NB, Nahlik L, Vogelzang NJ. Source: The Journal of Urology. 2002 April; 167(4): 1793. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11912419&dopt=Abstract
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Drug interactions as a cause of overanticoagulation and bleedings in Chinese patients receiving warfarin. Author(s): Chan TY. Source: Int J Clin Pharmacol Ther. 1998 July; 36(7): 403-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9707357&dopt=Abstract
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Effect of coenzyme Q10 and Ginkgo biloba on warfarin dosage in stable, long-term warfarin treated outpatients. A randomised, double blind, placebo-crossover trial. Author(s): Engelsen J, Nielsen JD, Winther K.
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Source: Thrombosis and Haemostasis. 2002 June; 87(6): 1075-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12083489&dopt=Abstract •
Effect of soy milk on warfarin efficacy. Author(s): Cambria-Kiely JA. Source: The Annals of Pharmacotherapy. 2002 December; 36(12): 1893-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12452752&dopt=Abstract
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Enhancement of warfarin response in a patient receiving etoposide and carboplatin chemotherapy. Author(s): Le AT, Hasson NK, Lum BL. Source: The Annals of Pharmacotherapy. 1997 September; 31(9): 1006-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9296241&dopt=Abstract
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Grapefruit juice and the response to warfarin. Author(s): Sullivan DM, Ford MA, Boyden TW. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 1998 August 1; 55(15): 1581-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9706183&dopt=Abstract
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Hepatic microsomal warfarin metabolism in warfarin-resistant and susceptible mouse strains: influence of pretreatment with cytochrome P-450 inducers. Author(s): Sutcliffe FA, MacNicoll AD, Gibson GG. Source: Chemico-Biological Interactions. 1990; 75(2): 171-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2369784&dopt=Abstract
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Herbal drug curbicin and anticoagulant effect with and without warfarin: possibly related to the vitamin E component. Author(s): Yue QY, Jansson K. Source: Journal of the American Geriatrics Society. 2001 June; 49(6): 838. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11454132&dopt=Abstract
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Herbs and the brain: friend or foe? The effects of ginkgo and garlic on warfarin use. Author(s): Evans V. Source: The Journal of Neuroscience Nursing : Journal of the American Association of Neuroscience Nurses. 2000 August; 32(4): 229-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10994537&dopt=Abstract
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Human plasma protein Z antigen: range in normal subjects and effect of warfarin therapy. Author(s): Miletich JP, Broze GJ Jr.
Alternative Medicine 101
Source: Blood. 1987 June; 69(6): 1580-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3580568&dopt=Abstract •
Induction of hepatic enzymes by methaqualone and effect on warfarin-induced hypoprothrombinemia. Author(s): Mathur PP, Smyth RD, Herczeg T, Reavey-Cantwell NH. Source: The Journal of Pharmacology and Experimental Therapeutics. 1976 January; 196(1): 204-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1246011&dopt=Abstract
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Inhibition of the hypoprothrombinemic effect of warfarin (Coumadin) by Ensure Plus, a dietary supplement. Author(s): Michaelson R, Kempin SJ, Navia B, Gold JW. Source: Clin Bull. 1980; 10(4): 171-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7214706&dopt=Abstract
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Inhibition of warfarin anticoagulation associated with chelation therapy. Author(s): Grebe HB, Gregory PJ. Source: Pharmacotherapy. 2002 August; 22(8): 1067-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12173793&dopt=Abstract
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INR elevation associated with diarrhea in a patient receiving warfarin. Author(s): Smith JK, Aljazairi A, Fuller SH. Source: The Annals of Pharmacotherapy. 1999 March; 33(3): 301-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10200853&dopt=Abstract
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Interaction between warfarin and danshen (Salvia miltiorrhiza). Author(s): Chan TY. Source: The Annals of Pharmacotherapy. 2001 April; 35(4): 501-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11302416&dopt=Abstract
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Interaction between warfarin and the herbal product quilinggao. Author(s): Wong AL, Chan TY. Source: The Annals of Pharmacotherapy. 2003 June; 37(6): 836-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12773074&dopt=Abstract
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Interaction of warfarin and nonsystemic gastrointestinal drugs. Author(s): Robinson DS, Benjamin DM, McCormack JJ. Source: Clinical Pharmacology and Therapeutics. 1971 May-June; 12(3): 491-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5567801&dopt=Abstract
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Interactions of warfarin with garlic, ginger, ginkgo, or ginseng: nature of the evidence. Author(s): Vaes LP, Chyka PA. Source: The Annals of Pharmacotherapy. 2000 December; 34(12): 1478-82. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11144706&dopt=Abstract
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Interactions of warfarin. Author(s): Rehulkova O. Source: Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2001 December; 145(2): 27-38. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12426769&dopt=Abstract
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Myocardial infarction after diet-induced warfarin resistance. Author(s): Walker FB 4th. Source: Archives of Internal Medicine. 1984 October; 144(10): 2089-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6486994&dopt=Abstract
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Orlistat enhances warfarin effect. Author(s): MacWalter RS, Fraser HW, Armstrong KM. Source: The Annals of Pharmacotherapy. 2003 April; 37(4): 510-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12659605&dopt=Abstract
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Pharmacokinetic interactions between warfarin and kangen-karyu, a Chinese traditional herbal medicine, and their synergistic action. Author(s): Makino T, Wakushima H, Okamoto T, Okukubo Y, Deguchi Y, Kano Y. Source: Journal of Ethnopharmacology. 2002 September; 82(1): 35-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12169403&dopt=Abstract
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Pharmacokinetics of warfarin in rabbits during short-term and long-term uraemia. Author(s): Tvedegaard E, Ladefoged J, Ladefoged O. Source: Journal of Veterinary Pharmacology and Therapeutics. 1981 June; 4(2): 141-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6818361&dopt=Abstract
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Possible influences of ginseng on the pharmacokinetics and pharmacodynamics of warfarin in rats. Author(s): Zhu M, Chan KW, Ng LS, Chang Q, Chang S, Li RC. Source: The Journal of Pharmacy and Pharmacology. 1999 February; 51(2): 175-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10217316&dopt=Abstract
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Possible interaction between warfarin and Lycium barbarum L. Author(s): Lam AY, Elmer GW, Mohutsky MA.
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Source: The Annals of Pharmacotherapy. 2001 October; 35(10): 1199-201. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11675844&dopt=Abstract •
Potential interaction between warfarin and boldo-fenugreek. Author(s): Lambert JP, Cormier A. Source: Pharmacotherapy. 2001 April; 21(4): 509-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11310527&dopt=Abstract
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Potential interactions between alternative therapies and warfarin. Author(s): Heck AM, DeWitt BA, Lukes AL. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 2000 July 1; 57(13): 1221-7; Quiz 122830. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10902065&dopt=Abstract
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Potentiation of warfarin by dong quai. Author(s): Page RL 2nd, Lawrence JD. Source: Pharmacotherapy. 1999 July; 19(7): 870-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10417036&dopt=Abstract
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Probable antagonism of warfarin by green tea. Author(s): Taylor JR, Wilt VM. Source: The Annals of Pharmacotherapy. 1999 April; 33(4): 426-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10332534&dopt=Abstract
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Probable interaction between warfarin and ginseng. Author(s): Janetzky K, Morreale AP. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 1997 March 15; 54(6): 692-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9075501&dopt=Abstract
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Psychologic and neuropsychologic functioning of patients with limited small-cell lung cancer treated with chemotherapy and radiation therapy with or without warfarin: a study by the Cancer and Leukemia Group B. Author(s): Ahles TA, Silberfarb PM, Herndon J 2nd, Maurer LH, Kornblith AB, Aisner J, Perry MC, Eaton WL, Zacharski LL, Green MR, Holland JC. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 1998 May; 16(5): 1954-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9586915&dopt=Abstract
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Racial background is a determinant of average warfarin dose required to maintain the INR between 2.0 and 3.0. Author(s): Blann A, Hewitt J, Siddiqui F, Bareford D.
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Source: British Journal of Haematology. 1999 October; 107(1): 207-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10520043&dopt=Abstract •
Randomized trial of chemotherapy and radiation therapy with or without warfarin for limited-stage small-cell lung cancer: a Cancer and Leukemia Group B study. Author(s): Maurer LH, Herndon JE 2nd, Hollis DR, Aisner J, Carey RW, Skarin AT, Perry MC, Eaton WL, Zacharski LL, Hammond S, Green MR. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 1997 November; 15(11): 3378-87. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9363869&dopt=Abstract
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Re: Does PC-SPES interact with warfarin? Author(s): Duncan GG. Source: The Journal of Urology. 2003 January; 169(1): 294-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12478174&dopt=Abstract
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Regioselective and stereoselective hydroxylation of R and S warfarin by different forms of purified cytochrome P-450 from rabbit liver. Author(s): Fasco MJ, Vatsis KP, Kaminsky LS, Coon MJ. Source: The Journal of Biological Chemistry. 1978 November 10; 253(21): 7813-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=701290&dopt=Abstract
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Spinal meningeal hematoma, warfarin therapy, and chiropractic adjustment. Author(s): Dabbert O, Freeman DG, Weis AJ. Source: Jama : the Journal of the American Medical Association. 1970 December 14; 214(11): 2058. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5536482&dopt=Abstract
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Stereoselective metabolism of conformational analogues of warfarin by betanaphthoflavone-inducible cytochrome P-450. Author(s): Heimark LD, Trager WF. Source: Journal of Medicinal Chemistry. 1985 April; 28(4): 503-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3981543&dopt=Abstract
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Studies on the biosynthesis of factor VII (proconvertin). The mode of action of warfarin. Author(s): Prydz H, Gaudernack G. Source: Biochimica Et Biophysica Acta. 1971 February 23; 230(2): 373-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4324764&dopt=Abstract
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The effect of EDTA in the electroimmunoassay of factor IX antigen in warfarintreated patients. Author(s): Yang HC.
Alternative Medicine 105
Source: Thrombosis Research. 1979; 15(1-2): 89-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=113906&dopt=Abstract •
The effects of Danshen (Salvia miltiorrhiza) on pharmacokinetics and pharmacodynamics of warfarin in rats. Author(s): Lo AC, Chan K, Yeung JH, Woo KS. Source: Eur J Drug Metab Pharmacokinet. 1992 October-December; 17(4): 257-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1301354&dopt=Abstract
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The effects of Danshen (Salvia miltiorrhiza) on warfarin pharmacodynamics and pharmacokinetics of warfarin enantiomers in rats. Author(s): Chan K, Lo AC, Yeung JH, Woo KS. Source: The Journal of Pharmacy and Pharmacology. 1995 May; 47(5): 402-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7494191&dopt=Abstract
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Therapy of acute thromboembolism with heparin and warfarin. Author(s): Carter BL. Source: Clin Pharm. 1991 July; 10(7): 503-18. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1860301&dopt=Abstract
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Thrombosis of a prosthetic aortic valve disclosing a hazardous interaction between warfarin and a commercial ginseng product. Author(s): Rosado MF. Source: Cardiology. 2003; 99(2): 111. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12711887&dopt=Abstract
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Use of herbal medicines by patients receiving warfarin. Author(s): Wong RS, Cheng G, Chan TY. Source: Drug Safety : an International Journal of Medical Toxicology and Drug Experience. 2003; 26(8): 585-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12825970&dopt=Abstract
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Warfarin and herbal supplements. A volatile combination. Author(s): Ezbianski AA. Source: Adv Nurse Pract. 2003 November; 11(11): 77-80. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14639889&dopt=Abstract
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Warfarin and hydroxyethylrutosides in deep vein thrombosis. Author(s): Eastham RD, Perham TG, Pocock PV. Source: British Medical Journal. 1972 November 25; 4(838): 491. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4653895&dopt=Abstract
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Warfarin antagonism of natto and increase in serum vitamin K by intake of natto. Author(s): Kudo T. Source: Artery. 1990; 17(4): 189-201. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2360879&dopt=Abstract
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Warfarin danshen interaction. Author(s): Cheng TO. Source: The Annals of Thoracic Surgery. 1999 March; 67(3): 894. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10215271&dopt=Abstract
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Warfarin interactions with Chinese traditional medicines: danshen and methyl salicylate medicated oil. Author(s): Tam LS, Chan TY, Leung WK, Critchley JA. Source: Aust N Z J Med. 1995 June; 25(3): 258. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7487701&dopt=Abstract
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Warfarin resistance associated with intravenous lipid administration. Author(s): Lutomski DM, Palascak JE, Bower RH. Source: Jpen. Journal of Parenteral and Enteral Nutrition. 1987 May-June; 11(3): 316-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3110450&dopt=Abstract
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Warfarin resistance associated with intravenous lipid administration: discussion of propofol and review of the literature. Author(s): MacLaren R, Wachsman BA, Swift DK, Kuhl DA. Source: Pharmacotherapy. 1997 November-December; 17(6): 1331-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9399621&dopt=Abstract
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Warfarin skin necrosis. The role of factor VII. Author(s): Jones RR, Cunningham J. Source: The British Journal of Dermatology. 1979 November; 101(5): 561-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=160244&dopt=Abstract
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Warfarin, etoposide, and vindesine interactions. Author(s): Ward K, Bitran JD. Source: Cancer Treat Rep. 1984 May; 68(5): 817-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6539172&dopt=Abstract
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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 warfarin; 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 Alzheimer's Disease Source: Integrative Medicine Communications; www.drkoop.com Atherosclerosis and Heart Disease Prevention Source: Prima Communications, Inc.www.personalhealthzone.com Bone Loss Source: Integrative Medicine Communications; www.drkoop.com Cancer Prevention (reducing the Risk) Source: Prima Communications, Inc.www.personalhealthzone.com Capillary Fragility Source: Healthnotes, Inc.; www.healthnotes.com Cardiovascular Disease Overview Source: Healthnotes, Inc.; www.healthnotes.com
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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 Depression 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 High Cholesterol Source: Prima Communications, Inc.www.personalhealthzone.com Hypertension Alternative names: High Blood Pressure Source: Prima Communications, Inc.www.personalhealthzone.com Menopause Source: Integrative Medicine Communications; www.drkoop.com Migraine Headaches Source: Prima Communications, Inc.www.personalhealthzone.com Mitral Valve Prolapse Source: Healthnotes, Inc.; www.healthnotes.com Nausea Source: Prima Communications, Inc.www.personalhealthzone.com Osteoporosis Source: Integrative Medicine Communications; www.drkoop.com Osteoporosis Source: Prima Communications, Inc.www.personalhealthzone.com Prostate Cancer Source: Healthnotes, Inc.; www.healthnotes.com
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Psoriasis Source: Prima Communications, Inc.www.personalhealthzone.com Rheumatoid Arthritis Source: Prima Communications, Inc.www.personalhealthzone.com Stroke Source: Healthnotes, Inc.; www.healthnotes.com Transient Ischemic Attacks Source: Integrative Medicine Communications; www.drkoop.com Varicose Veins Source: Prima Communications, Inc.www.personalhealthzone.com •
Herbs and Supplements Allium Sativum Alternative names: Garlic Source: Integrative Medicine Communications; www.drkoop.com American Ginseng Alternative names: Ginseng, American Source: Integrative Medicine Communications; www.drkoop.com Angelica Sinensis Alternative names: Dong Quai Source: Integrative Medicine Communications; www.drkoop.com Aortic Glycosaminoglycans Source: Prima Communications, Inc.www.personalhealthzone.com Asian Ginseng Alternative names: Ginseng, Asian Source: Integrative Medicine Communications; www.drkoop.com Aspirin Source: Healthnotes, Inc.; www.healthnotes.com Bromelain 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
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Camellia Sinensis Alternative names: Green Tea Source: Integrative Medicine Communications; www.drkoop.com Chamaemelum Nobile Alternative names: Roman Chamomile Source: Integrative Medicine Communications; www.drkoop.com Chinese Angelica Alternative names: Dong Quai Source: Integrative Medicine Communications; www.drkoop.com Coenzyme Q10 Source: Healthnotes, Inc.; www.healthnotes.com Coenzyme Q10 Alternative names: CoQ10 Source: Integrative Medicine Communications; www.drkoop.com Coleus Forskohlii Source: Prima Communications, Inc.www.personalhealthzone.com CoQ10 Alternative names: Coenzyme Q10 Source: Integrative Medicine Communications; www.drkoop.com Danggui Alternative names: Dong Quai Source: Integrative Medicine Communications; www.drkoop.com Devil's Claw Alternative names: Harpagophytum procumbens Source: Integrative Medicine Communications; www.drkoop.com Devil's Claw Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,970,00.html Digestive Enzymes Source: Healthnotes, Inc.; www.healthnotes.com Dipyridamole Source: Healthnotes, Inc.; www.healthnotes.com Dong Quai Alternative names: Angelica sinensis Source: Integrative Medicine Communications; www.drkoop.com Feverfew Source: Prima Communications, Inc.www.personalhealthzone.com
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German Chamomile Alternative names: Matricaria recutita 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 Source: Healthnotes, Inc.; www.healthnotes.com Ginkgo Biloba Alternative names: Maidenhair Tree Source: Integrative Medicine Communications; www.drkoop.com Ginseng Source: Prima Communications, Inc.www.personalhealthzone.com Goldenseal Alternative names: Hydrastis canadensis Source: Integrative Medicine Communications; www.drkoop.com Green Tea Source: Healthnotes, Inc.; www.healthnotes.com Green Tea Alternative names: Camellia sinensis Source: Integrative Medicine Communications; www.drkoop.com Green Tea Source: Prima Communications, Inc.www.personalhealthzone.com Harpagophytum Procumbens Alternative names: Devil's Claw Source: Integrative Medicine Communications; www.drkoop.com Harpagophytum Zeyheri Alternative names: Devil's Claw Source: Integrative Medicine Communications; www.drkoop.com 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 Hydrastis Canadensis Source: Integrative Medicine Communications; www.drkoop.com 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 Matricaria Recutita Source: Integrative Medicine Communications; www.drkoop.com Menadione Alternative names: Vitamin K Source: Integrative Medicine Communications; www.drkoop.com Menaphthone Alternative names: Vitamin K Source: Integrative Medicine Communications; www.drkoop.com Menaquinone Alternative names: Vitamin K 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 OPCS (Oligomeric Proanthocyanidins) Source: Prima Communications, Inc.www.personalhealthzone.com Panax Alternative names: Ginseng; Panax ginseng Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org
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Panax Ginseng Alternative names: Asian Ginseng Source: Integrative Medicine Communications; www.drkoop.com Panax Quinquefolium Alternative names: American Ginseng Source: Integrative Medicine Communications; www.drkoop.com Phylloquinone Alternative names: Vitamin K Source: Integrative Medicine Communications; www.drkoop.com Plantago Psyllium Alternative names: Psyllium, Ispaghula; Plantago psyllium/ovata Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Primidone Alternative names: Mysoline Source: Prima Communications, Inc.www.personalhealthzone.com Red Clover Source: Integrative Medicine Communications; www.drkoop.com Red Clover Source: Prima Communications, Inc.www.personalhealthzone.com Reishi Source: Prima Communications, Inc.www.personalhealthzone.com Roman Chamomile Alternative names: Chamaemelum nobile Source: Integrative Medicine Communications; www.drkoop.com St. John's Wort Alternative names: Hypericum perforatum Source: Integrative Medicine Communications; www.drkoop.com St. John's Wort Source: Prima Communications, Inc.www.personalhealthzone.com Tanacetum Alternative names: Feverfew; Tanacetum parthenium (L.) Schultz-Bip. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Tang Kuei Alternative names: Dong Quai Source: Integrative Medicine Communications; www.drkoop.com Ticlopidine Source: Healthnotes, Inc.; www.healthnotes.com
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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
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 WARFARIN Overview In this chapter, we will give you a bibliography on recent dissertations relating to warfarin. 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 “warfarin” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on warfarin, we have not necessarily excluded non-medical dissertations in this bibliography.
Dissertations on Warfarin 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 warfarin. 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: •
Warfarin Therapy and Risk of Bladder Cancer by Blumentals, William Andrew; PhD from University of South Florida, 2002, 72 pages http://wwwlib.umi.com/dissertations/fullcit/3052632
Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.
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CHAPTER 5. CLINICAL TRIALS AND WARFARIN Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning warfarin.
Recent Trials on Warfarin The following is a list of recent trials dedicated to warfarin.8 Further information on a trial is available at the Web site indicated. •
A safety and efficacy trial evaluating the use of SanOrg34006 compared to warfarin or acenocoumarol in patients with atrial fibrillation Condition(s): Atrial Fibrillation Study Status: This study is currently recruiting patients. Sponsor(s): Organon Purpose - Excerpt: This trial will include patients who have a heart condition called atrial fibrillation. Atrial fibrillation is an abnormal rhythm (irregular beat) in the heart. Patients with atrial fibrillation have an increased chance for a blood clot to form in the heart and move to other blood vessels in the body and cause obstruction. This obstruction may damage tissue. For example, a blood clot plugging a vessel in the brain could cause a stroke. Therefore, patients with atrial fibrillation may be given anticoagulant (blood-thinning) tablets such as warfarin or acenocoumarol. The purpose of this study is to compare the safety and effectiveness of a new injectable anticoagulant drug that is administered once weekly, SanOrg34006 (International Nonproprietary Name - idraparinux sodium), with warfarin or acenocoumarol tablets. Assignment to either SanOrg34006 (idraparinux sodium) Injection or vitamin K antagonist (warfarin or acenocoumarol) tablets will be purely by chance and will be known by both patients and their doctors. Phase(s): Phase III Study Type: Interventional
8
These are listed at www.ClinicalTrials.gov.
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Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00070655 •
Aspirin Or Warfarin To Prevent Stroke Condition(s): Stroke; Cerebral Infarction; Atherosclerosis; Constriction, Pathologic Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Neurological Disorders and Stroke (NINDS) Purpose - Excerpt: The purpose of this study is to determine whether aspirin or warfarin is more effective in preventing stroke in patients with intracranial stenosis. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004728
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Warfarin in Preventing Blood Clots in Cancer Patients With Central Venous Catheters Condition(s): Thromboembolism Study Status: This study is currently recruiting patients. Sponsor(s): Cancer Research Campaign Clinical Trials Centre Purpose - Excerpt: RATIONALE: Warfarin may be effective in preventing the formation of blood clots in patients with central venous catheters. PURPOSE: Randomized clinical trial to study the effectiveness of warfarin in preventing blood clots in cancer patients who have central venous catheters. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00024297
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Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) Trial Condition(s): Heart Disease; Stroke; Ischemic Heart Disease; Myocardial Infarction; Atrial Fibrillation Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Neurological Disorders and Stroke (NINDS) Purpose - Excerpt: The purpose of this study is to determine which of two treatments, Warfarin or aspirin, is better for preventing death and stroke in patients with poor heart function. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00041938
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•
Are Aspirin, Warfarin, and Clopidogrel Equally Effective in the Treatment of Patients With Symptomatic CHF and Reduced Ejection Fraction? Condition(s): NYHA Class II, III or IV CHF; Left ventricular ejection fraction less than or equal to 35% Study Status: This study is no longer recruiting patients. Sponsor(s): Department of Veterans Affairs; Department of Veterans Affairs Cooperative Studies Program; Canadian Regional Coordinating Center; UK Regional Coordinating Center; Economic Analysis Lab; Echo Core Lab; Sanofi-Synthelabo; Bristol-Myers Squibb; Dupont Pharmaceuticals Purpose - Excerpt: Whether patients with chronic heart failure (CHF) should be anticoagulated is one of the oldest unresolved questions in cardiovascular therapeutics. Some authorities do not recommend anticoagulation for CHF patients in sinus rhythm, others recommend anticoagulation in patients with primary cardiomyopathy, and still others consider it more appropriate in patients with coronary artery disease (CAD). This absence of consensus reflects the lack of evidence in this area and different outlooks on the objectives of such therapy (e.g., prevention of arterial emboli or reduction in vascular events). Phase(s): Phase III; MEDLINEplus consumer health information Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00007683
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Combination Chemotherapy Plus Warfarin in Treating Patients With Prostate Cancer Condition(s): stage III prostate cancer; stage IV prostate cancer; Thromboembolism; recurrent prostate cancer Study Status: This study is no longer recruiting patients. Sponsor(s): National Cancer Institute (NCI); Memorial Sloan-Kettering Cancer Center Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. Anticoagulant drugs such as warfarin may reduce the risk of blood clots. PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy plus warfarin in treating patients who have prostate cancer. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00014352
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Warfarin Versus Aspirin Recurrent Stroke Study Condition(s): Stroke Study Status: This study is completed. Sponsor(s): National Institute of Neurological Disorders and Stroke (NINDS) Purpose - Excerpt: The goal of this study is to compare aspirin to warfarin for the prevention of recurrent stroke. Phase(s): Phase III
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Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00027066
Keeping Current on Clinical Trials The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to the Web site at http://www.clinicaltrials.gov/ and search by “warfarin” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: •
For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/
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For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html
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For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/
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For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm
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For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm
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For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm
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For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp
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For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm
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For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/
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For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm
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For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm
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•
For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm
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For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm
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For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm
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For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials
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CHAPTER 6. PATENTS ON WARFARIN Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.9 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “warfarin” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on warfarin, we have not necessarily excluded non-medical patents in this bibliography.
Patents on Warfarin By performing a patent search focusing on warfarin, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We
9Adapted
from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.
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will tell you how to obtain this information later in the chapter. The following is an example of the type of information that you can expect to obtain from a patent search on warfarin: •
4-Hydroxycoumarins Inventor(s): Hadler; Malcolm Ronald (Tarporley, EN), Shadbolt; Roy Stanley (Westminister Park, EN) Assignee(s): Ward Blenkinsop and Company Limited (EN) Patent Number: 3,957,824 Date filed: May 22, 1974 Abstract: Novel 4-hydroxy coumarins substituted in the 3 position with substituted tetrahydronaphthyl groups are described. A method of making them by condensing 4hydroxy coumarin with hydroxyl or halogeno derivatives of the substituted tetrahydronaphthalenes is described. The compounds of the invention are potent anticoagulants finding typical uses as rodenticides. As rodenticides they are particularly effective against rodents resistant to such agents as Warfarin, Coumatetralyl, Diphacinone and Pival. Excerpt(s): Where m is 1 or 2, and R.sup.4 is the same or different and is a halogen atom, a straight or branched chain alkyl or alkoxy group, preferably containing at least 2, more preferably from 5 to 12 carbon atoms, a cycloalkyl, preferably cyclohexyl group, an aralkyl, preferably.alpha.-aralkyl group, a phenyl or a phenoxy group, or a halogeno, preferably para halogeno, substituted derivative thereof. The halogen atom or atoms are preferably chlorine or bromine. Where m is 1, R.sup.4 is preferably in the para position and when m is 2 one of the R.sup. 4 groups is preferably in the para position. Preferably R.sup.3 contains at least 1 but not more than 3 and optimally not more than 2 halogen atoms. R.sup.1, r.sup.2 and R.sup.3 have the meanings given previously and Hal is halogen, preferably chlorine or bromine. Compounds of structure IV may be prepared from compounds of general structure III by treatment with reagents such as phosphorus tribromide, phosphorus trichloride or thionyl chloride in an inert solvent such as methylene chloride, chloroform or carbon tetrachloride. Web site: http://www.delphion.com/details?pn=US03957824__
•
Artificial maple concentrate attractant rodent baits Inventor(s): Hollis, Jr.; John P. (7146 Spring Ter., San Antonio, TX 78249) Assignee(s): none reported Patent Number: 4,842,861 Date filed: May 26, 1988 Abstract: This application discloses rodenticide and rodent-attracting compositions containing sugar-free maple concentrate attractant and Warfarin-masking saccharine (sodium). The disclosed compositions have greatly improved acceptability to the rodents and have a long storage life. Excerpt(s): Rodents--rats and mice--have been associated with man since his earliest developments in agriculture, habitation and accumulation of foodstuffs. Rats in particular consume and contaminate, with feces, urine and decomposing matter, large amounts of agricultural products and stored food. Rats and mice carry and spread
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within the environment several infectious agents which cause diseases in man and in the lower animals. Rodents are a major pest problem worlwide; their control is pursued primarily with dangerous chemicals toxic also to man and domestic animals. The economics of rodent control have imposed constraints upon use of extremely toxic chemicals and expensive baits. Prior art has made use of unattractive, cheaplyformulated baits containing the active ingredient Warfarin, a multiple-feeding anticoagulant toxicant and a variety of similar rodenticides. Attempts to increase attractiveness of a Warfarin bait with maple syrup and maple formulations with sugar as a masking agent for Warfarin in patent application Ser. No. 168,368 were rejected on the ground that maple was sugar and sugar had been patented as an attractant. Therefore a CIP to 168,368, accepted as patent application Ser. No. 848,639, was presented, although in improper fashion, involving the use of sugar-free maple concentrate with saccharine (sodium) as a masking agent. This application was rejected on the grounds that sweeteners including saccharine had been shown attractant in rodent baits, and on the basis of improper claims; the alleged merits of sugar-free artificial maple concentrate were not addressed. The purpose of this CIP to Ser. No. 848,639 is to put the issue of artificial maple concentrates as attractant and saccharine (sodium) as masking agent for rodenticides in proper form with claims that match an area of opportunity about them which is virgin to practice, patents or literature. Web site: http://www.delphion.com/details?pn=US04842861__ •
Cyclic compounds useful as inhibitors of platelet glycoprotein IIB/IIIA Inventor(s): Degrado; William F. (Moylan, PA), Jackson; Sharon A. (Chadds Ford, PA), Mousa; Shaker A. (Lincoln University, PA), Parthasarathy; Anju (New Castle, DE), Rafalski; Maria (Wilmington, DE), Sworin; Michael (Newark, DE) Assignee(s): The DuPont Merck Pharmaceutical Company (Wilmington, DE) Patent Number: 5,635,477 Date filed: June 5, 1995 Excerpt(s): This invention relates to novel cyclic compounds containing carbocyclic ring systems useful as antagonists of the platelet glycoprotein IIb/IIIa complex, to pharmaceutical compositions containing such cyclic compounds, with or without other therapeutic agents, and to methods of using these compounds, with or without other therapeutic agents, for the inhibition of platelet aggregation, as thrombolytics, and/or for the treatment of other thromboembolic disorders. Activation of platelets and the resulting platelet aggregation and secretion of factors by the platelets has been associated with different pathophysiological conditions including cardiovascular and cerebrovascular thromboembolic disorders, for example, the thromboembolic disorders associated with unstable angina, myocardial infarction, transient ischemic attack, stroke, atherosclerosis and diabetes. The contribution of platelets to these disease processes stems from their ability to form aggregates, or platelet thrombi, especially in the arterial wall following injury or plaque rupture. Platelets are known to play an essential role in the maintenance of hemostasis and in the pathogenesis of arterial thrombosis. Platelet activation has been shown to be enhanced during coronary thrombolysis which can lead to delayed reperfusion and reocclusion. Clinical studies with aspirin, ticlopidine and a monoclonal antibody for platelet glycoprotein IIb/IIIa provide biochemical evidence for platelet involvement in unstable angina, early stage of acute myocardial infarction, transient ischemic attack, cerebral ischemia, and stroke. Web site: http://www.delphion.com/details?pn=US05635477__
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Immunoassay means and methods useful in human native prothrombin and human abnormal prothorombin determinations Inventor(s): Blanchard; Rita A. (Newton, MA), Furie; Barbara C. (Wellesley, MA), Furie; Bruce E. (Wellesley, MA) Assignee(s): New England Medical Center Hospitals, Inc. (Boston, MA) Patent Number: 4,769,320 Date filed: October 15, 1984 Abstract: Antibodies which form immune complexes with human native prothrombin only, in the presence of mixtures of human native prothrombin and human abnormal prothrombin as well as antibodies which form antibody antigen complexes with human abnormal prothrombin in the presence of such mixtures have been obtained. Immunoassay techniques are used for qualitative and quantitative determinations of these antigens in human plasma or serum. Unique methods of obtaining the antibodies are described including obtaining antibodies to native prothrombin by dissociation of antigen antibody complexes formed in the presence of calcium ions with a material having a greater affinity constant for binding with calcium ions than does prothrombin. Dissociation of the complex in this manner yields human native prothrombin antibodies which are specific and non-reactive with human abnormal prothrombin. A process is described in which assays are applied to the sensitive detection of vitamin K deficiency and various forms of liver disease including hepatocellular carcinoma, and to monitoring of anticoagulant therapy with sodium warfarin. The invention described herein was made in the course of working under a grant from the Department of Health and Human Services. Excerpt(s): Prothrombin is a vitamin K dependent plasma protein involved in the final stages of blood coagulation as has been well-known for some time. It has a molecular weight of about 72,000 and contains about 12% carbohydrate. Prothrombin is a calciumbinding protein that undergoes a conformational transition in the presence of calcium as is known. The proteolytic activation of prothrombin to thrombin is a critical step in normal hemostasis. Prothrombin is synthesized in the liver where a prothrombin precursor undergoes post-translational modification to yield the functional form of prothrombin which is known as "native prothrombin" and contains.gamma.carboxyglutamic acid. In the presence of vitamin K antagonists, such as sodium warfarin also known as Coumadin, a trademarked product of Endo Laboratories division of DuPont Corp. of Wilmington, Del., or in the absence of vitamin K, the prothrombin activity in the blood may be significantly diminished. This can be measured indirectly by the prothrombin time, a one-stage coagulation assay, or by direct measurement of prothrombin coagulant activity using prothrombin deficient substrate plasma. Severe liver disease may also be associated with low plasma prothrombin activity. Thus impaired synthesis of protein (liver disease), inadequate supplies of vitamin K (vitamin K deficiency) or drugs that inhibit the action of vitamin K (sodium warfarin) lead to diminished plasma prothrombin activity in humans and other mammals. Coumadin is the trade name for warfarin. When Coumadin is used as an oral anticoagulant as is widely done in the therapy or prevention of thrombotic disease, it lowers the activity of vitamin K dependent blood coagulation proteins such as prothrombin. The appropriate Coumadin dose is established by monitoring the prothrombin time. The prothrombin time is maintained at one and a half to two and a half times that obtained with normal plasma. In 1968 an altered from of prothrombin known as "abnormal prothrombin" and "human abnormal prothrombin" as opposed to human native prothrombin was discovered in the plasma of human patients treated
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with sodium warfarin. Abnormal prothrombin has low prothrombin activity but cross reacts with many prothrombin antisera. Abnormal prothrombin from bovine blood was first isolated in 1972. Such abnormal prothrombin was found to have about 3% of the coagulant activity of an equivalent amount of native prothrombin. Otherwise, the molecular weight, carbohydrate composition and amino acid composition of the acid hydrolysate were substantially identical within experimental error. In the early 70's it was discovered that bovine abnormal prothrombin unlike prothrombin does not bind to barium salts and does not bind to calcium ions. It was subsequently shown that the functional differences between abnormal and native prothrombin relate to the structural differences between these proteins and full prothrombin function requires intact calcium binding sites. In the mid-70's it was discovered that a theretofore unknown amino acid.gamma.-carboxyglutamic acid occurred in bovine prothrombin and was lacking in abnormal bovine prothrombin. This amino acid seemed to be required for the full expression of prothrombin coagulant activity. Abnormal prothrombin is known to have no coagulant activity, does not bind metal ions and does not contain.gamma.carboxyglutamic acid. Other researchers have theorized that prothrombin is synthesized in the liver in a precursor form containing glutamic acid instead of.gamma.carboxyglutamic acid. A carboxylation process in the liver modifies glutamic acid to form.gamma.-carboxyglutamic acid. This enzyme system requires vitamin K and is inhibited by vitamin K antagonists. Web site: http://www.delphion.com/details?pn=US04769320__ •
Microcrystalline 3-(alpha-acetonylbenzyl)-4-hydroxycoumarin methods of making
(warfarin)
and
Inventor(s): Badran; Nasri W. (428 Oxford Rd., New Rochelle, NY 10804) Assignee(s): Badran; Nasri W. (New Rochelle, NY) Patent Number: 4,113,744 Date filed: August 13, 1974 Abstract: Microcrystalline 3-(alpha-acetonylbenzyl)-4-hydroxy coumarin (warfarin), having a crystal size not greater than 4.0 microns, is stable for long periods of time, is advantageous in that it is rapidly absorbed from the gastrointestinal tract and thus provides a highly desirable level of bioavailability not previously possible. It is crystallized from a buffered alkaline solution of warfarin by acidification thereof. Compositions thereof are useful for anticoagulant and rodenticide purposes, and methods of making such compositions and of using the new microcrystalline form of warfarin for such purposes are disclosed. Excerpt(s): Warfarin; microcrystalline warfarin; anticoagulants; rodenticides. The compound 3-(alpha-acetonylbenzyl)-4-hydroxy-coumarin (warfarin) is well-established and widely-employed as an oral anticoagulant and rodenticide. The rodenticide effect of the compound is due to the anticoagulant and blood thinning effect of the compound acting as an anticoagulant. The compound 3-(alpha-acetonylbenzyl)-4-hydroxycoumarin exists in both enol (acid) and keto configurations. The enol form is generically known as warfarin acid and is adopted by the U.S.P. XVIII as the reference standard for purity, being considered the active compound, despite its normal use in the form of its sodium salt. This form will hereinafter be referred to as warfarin acid, enol warfarin, or simply warfarin. Web site: http://www.delphion.com/details?pn=US04113744__
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Non-thrombogenic and anti-thrombogenic polymers Inventor(s): Luthra; Ajay Kumar (219 Somervell Road, South Harrow, Middlesex HA2 8UA, GB), Sandhu; Shivpal Singh (63 Lascelles Road, Slough, Berkshire SL3 7PW, GB) Assignee(s): none reported Patent Number: 6,096,798 Date filed: April 30, 1999 Abstract: Polymers having non-thrombogenic properties can be prepared by copolymerizing monomers of at least three classes selected from (a) monomers having sulphate groups, (b) monomers having sulphonate groups, (c) monomers having sulphamate groups, (d) monomers having polyoxyalkylene ether groups, and (e) monomers having zwitterionic groups. The polymers can additionally be provided with anti-thrombogenic properties by including an additional comonomer having a pendant heparin (or hirudin, warfarin or hyaluronic acid) group. The polymers can be used as coating materials for medical devices, such as tubing or connectors, in order to provide them with non-thrombogenic, and optionally anti-thrombogenic, properties. Excerpt(s): In schematic diagrams of this kind, as used herein, the designated side chains or groups can occur in any order and in any relative proportions along the polymer backbone. In polymers of Type 1 the non-thrombogenic (NON-TH) component may consist of non-ionic hydrophilic domains, ionic domains, zwitterionic domains or combinations of such domains. In novel Type 1 polymers in accordance with the invention, such non-thrombogenic components may be selected from, but are not limited to, polymerisable sulphonates, polymerisable sulphates, polymerisable Nsulphates (also known as sulphamates), polymerisable zwitterionic compounds, and polymerisable polyethylene glycols. When we synthesised polymers of Type 1, without the anti-thrombogenic component, and coated various medical devices, we found blood cell and protein deposition reduced by greater than 90%. Greatly reduced (>95%) activation of white cells, platelets and complement was observed. This type of synthetic polymer can be described as a non-thrombogenic polymer. The non-thrombogenic Type 1 polymer, as described, was synthesised with polymerisable Heparin to give a Type 2 polymer. Surprisingly, the activity of the heparin was retained in the Type 2 polymer and such polymers, when coated on to medical devices, had the additional property of reducing the thrombin-antithrombin complex concentration. This inclusion of heparin into the non-thrombogenic polymer gave a new polymer which additionally exhibited anti-thrombogenic properties. Web site: http://www.delphion.com/details?pn=US06096798__
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Oral anticoagulant/platelet inhibitor low dose formulation Inventor(s): Addicks; William J. (Wilmington, DE), Mollica; Joseph A. (Rockland, DE), Slatko; Gary H. (Chadds Ford, PA) Assignee(s): Du Pont Mereck Pharmaceutical Company (Wilmington, DE) Patent Number: 5,041,430 Date filed: September 18, 1989 Abstract: There are disclosed combination products useful for the treatment and/or prevention of a first or recurrent myocardial infarction or a first or recurrent stroke. Said combination products comprise low doses of an oral anticoagulant, preferably warfarin
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and platelet inhibiting agents, including non-steroidal antiinflammatory agents and preferrably aspirin. Excerpt(s): This invention relates to combination products comprising low doses of oral anticoagulants, such as warfarin, and low doses of inhibitors of platelet function (e.g., aggregation, adhesion) such as non-steroidal antiinflammatory agents, and preferably aspirin, in a single dosage form. Further, this invention relates to methods of using these low dose combination products for the prevention and/or treatment of first or recurrent myocardial infarction or the prevention and/or treatment of first or recurrent stroke. Recent advances in the understanding of the pathogenic factors leading to the acute coronary ischemic syndromes of unstable angina, myocardial infarction and ischemic sudden death, and acute cerebrovascular ischemic syndromes like transient ischemic attacks and stroke have demonstrated the individual importance of two compounds in particular, acetyl salicylic acid, hereinafter referred to as aspirin or ASA, and warfarin, in the prevention and/or treatment of these syndromes. Recently the value of antithrombotic therapy with high-dose aspirin in unstable angina has been conclusively demonstrated by two randomized, placebo-controlled, double-blind trials. See generally Lewis, et al. "Protective Effects of Aspirin Against Acute Myocardial Infarction and Death in Men with Aspirin " Results of a Veterans Cooperative Study, New England Journal of Medicine, 309: 396 (1983) and Cairns, et al.: "Aspirin, Sulfinpyrazone or Both in Unstable Angina: Results of a Canadian Multicenter Trial". New England Journal of Medicine, 313: 1369, (1985). Also, the recently pooled results of several studies suggest that long-term high-dose oral anticoagulant therapy may reduce the rate of recurrence of myocardial infarction by about 20%. [Fuster, et. al, (1988) Perspective, "Insights into the Pathogenesis of Acute Ischemic Syndromes", 77, No. 6, pp 1213-1220]. Traditionally, the simultaneous use of warfarin and aspirin at high doses has been relatively contraindicated. It has been a pervasive practice in the medical community to use these agents on an either/or basis. This practice was largely due to medical literature reporting undesirable clinical and pharmacologic interactions of the two drugs at high doses. Clinically, the propensity of aspirin, at high doses, to cause gastric mucosal erosion/ulceration, when dosed with an oral anticoagulant (warfarin) has led to a high reported incidence of exaggerated gastrointestinal (GI) bleeding with the high dose combination. Pharmacologically, aspirin at high doses also acts synergistically with warfarin to elevate the prothrombin time assay level for a given dose of warfarin. In light of recent advances in the study of the acute coronary syndromes and the recognition of the individual benefits that aspirin and warfarin provide in treating and/or preventing these syndromes, there is a need for a combination product wherein an oral anticoagulant such as warfarin and an antiplatelet agent, such as aspirin or a non-aspirin-non-steroidal antiinflammatory agent are present in a low dose ratio. The combination permits the use of doses below those currently accepted as "therapeutic" in the medical literature, in other words, doses at which the beneficial effects of the two agents are favored over the dose related side effects associated with simultaneous administration of currently accepted, high doses of the two agents. Web site: http://www.delphion.com/details?pn=US05041430__
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Pharmaceutical drug dosage forms providing different release rates Inventor(s): Bardsley; Hazel Judith (Cambridge, GB), Gilbert; Julian Clive (Cambridge, GB), Richards; Andrew John McGlashan (Cambridge, GB) Assignee(s): Darwin Discovery Limited (GB) Patent Number: 6,056,968 Date filed: March 11, 1998 Abstract: A pharmaceutical dosage form comprises, in one portion thereof, a substantially single (+)-enantiomer of a chiral drug other than verapamil and, in another, separate portion thereof, a substantially single (-)-enantiomer of the drug wherein, in use, the different enantiomers are released at different rates from the dosage form. The dosage form is useful for administration of chiral drugs where both enantiomers have a valid pharmacological input, and where a clinical benefit may be realised by controlling the release rates of those enantiomers. Examples of such drugs include, in particular, tramadol and warfarin. Excerpt(s): This invention relates to the discovery of novel pharmaceutical dosage forms of chiral drugs. The separate enantiomers of some chiral drugs have different therapeutic properties, and/or mechanisms of action and yet in some cases it may still be desirable to dose both enantiomers together. However, where the pharmacokinetic properties of the separate enantiomers are different, for instance due to differences in the rates at which they are metabolised, the ratio of the different enantiomers changes with time after initial dosing, which can lead to reduced efficacy of the drug. The actual enantiomeric ratio at any one time may be dependent upon a number of factors, and may be further complicated if different dosage forms provide different enantiomeric ratios. Effects such as these have been observed with the different enantiomers of verapamil, for instance see Longstreth, J.A. Clin. Pharmacol. (1993) 18 (2nd Edition): 315-336 and Gupta et al., Eur. J. Pharm. Biopharm. (1996) 42(1): 74-81. According to the present invention, a pharmaceutical dosage form comprises, in one portion thereof, a substantially single (+)-enantiomer of a chiral drug other than verapamil and, in another, separate, portion thereof, a substantially single (-)-enantiomer of the drug, wherein, in use, the different enantiomers are released at different rates from the dosage form. Web site: http://www.delphion.com/details?pn=US06056968__
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Preparation of warfarin sodium from warfarin sodium-2-propanol clathrate by solvent expulsion Inventor(s): Bercovici; Sorin (Kiriat Ono, IL), Chernyak; Shimon (Yokneam Ilit, IL), Ulanenko; Konstantin (Natania, IL) Assignee(s): Taro Pharmaceutical Industries Ltd. (Haifa Bay, IL) Patent Number: 6,610,862 Date filed: February 28, 2001 Abstract: The present invention is a method for producing warfarin sodium from warfarin sodium 2-propanol clathrate by thermal, nondestructive solvent expulsion. The solvent expulsion is conducted under conditions of controlled heat transfer whereby the 2-propanol is expelled from the warfarin sodium 2-propanol clathrate without decomposition of warfarin sodium or the clathrate. Heating is conducted the
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clathrate at a temperature from about 100.degree. C. to about 170.degree. C. in an active oven under air or in an inert atmosphere and at partial pressures ranging from that of a relative vacuum to atmospheric pressure. The invention also relates to pure warfarin sodium prepared according to the method of the invention and pharmaceutical compositions containing warfarin sodium. Excerpt(s): The present invention relates to a process for preparation of warfarin sodium. More specifically, the present invention relates to a process for preparing warfarin sodium from warfarin sodium 2-propanol clathrate by solvent expulsion. According to U.S. Pat. No. 3,192,232, warfarin sodium prepared by existing methods often has as undesirable slight yellow color. (See also, U.S. Pat. No. 3,077,481). U.S. Pat. No. 3,246,013 also emphasizes the difficulties encountered with the preparation of a high purity warfarin sodium. This patent discloses that the removal of the 2-propanol solvent from warfarin sodium 2-propanol clathrate cannot be achieved even with heating at 100.degree. C. over P.sub.2 O.sub.5 for 3-5 hours in a high vacuum (0.1 mm Hg). U.S. Pat. No. 3,077,481 further discloses that heating the clathrate at higher temperatures (145.degree. C.) in air at a high vacuum (1.0 mm Hg) for prolonged time periods (24 hours) results in undesirable decomposition. Also, heating at still higher temperatures (230.degree. C.), while successfully removing 2-propanol from the clathrate, results in rapid decomposition. Web site: http://www.delphion.com/details?pn=US06610862__ •
Rodenticidal compositions containing 2-chloro-3-phytyl-1,4-naphthaquinone and warfarin Inventor(s): Suttie; John W. (Madison, WI) Assignee(s): Wisconsin Alumni Research Foundation (Madison, WI) Patent Number: 4,021,568 Date filed: May 12, 1975 Abstract: A rodenticide suitable for the control of rat populations containing anticoagulant rodenticide-resistant rats comprising as the active rodenticidal ingredients 2-chloro-3-phytyl-1,4-naphthaquinone and a 3-substituted-4-hydroxycoumarin anticoagulant or a 2-substituted 1,3 indandione. Excerpt(s): This invention relates to rodenticides and food baits containing them. More specifically, this invention relates to anticoagulant-type rodenticides. Certain indandione derivatives and 3-substituted 4-hydroxycoumarin anticoagulant rodenticides, particularly warfarin, because of their efficacy and safety, have, for many years, been the rodenticides of choice over the quick-acting stomach poisons. it is recognized that these anticoagulant rodenticides function by suppressing the synthesis of the vitamin K-dependent clotting factors in the rodent and causing internal hemorrhaging. Such rodenticides are multiple dose baits, i.e., they normally have to be eaten over a period of about 3-6 days in order to be effective. Web site: http://www.delphion.com/details?pn=US04021568__
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Syntheses based on 2-hydroxyacetophenone Inventor(s): Aslam; Mohammad (Corpus Christi, TX), Brown, II; Charles H. (North Kingstown, RI), Fitzhenry; Sharon R. (Foxboro, MA), McDonough; Joseph A. (West Greenwich, RI), Uwaydah; Ibrahim M. (Corpus Christi, TX) Assignee(s): Hoechst Celanese Corporation (Somerville, NJ) Patent Number: 5,696,274 Date filed: May 22, 1996 Abstract: The present invention provides processes which are flexible, cost effective, and commercially viable methods of manufacturing or producing products from 2hydroxyacetophenone (2-HAP).Of particular interest of the available products are 4hydroxycoumarin, warfarin-alkali salt, preferably warfarin sodium and warfarin-alkali salt-isopropyl alcohol (2-propanol) complex, more preferably warfarin-sodiumisopropyl alcohol complex.As is known, these compounds are useful as vitamin K dependent anticoagulants in the treatment of humans and animals. In different doses, they are also useful as rodenticide.The inventive process involves contacting 2-HAP, carbonate ester and effective base followed by treatment with an unsaturated ketone and phase transfer catalyst to ultimately yield product. Excerpt(s): This is a NON-PROVISIONAL PATENT APPLICATION, said application claiming the benefit under 35 U.S.C.sctn.119(e) of a Provisional Patent Application, Application Number 60/009,416, filed on Dec. 28, 1995, and said APPLICATION being executed as a Non-Provisional application for filing under 35 USC 111(a) and 1.53(b)(1) concurrently herewith. This invention relates to compounds which may be synthesized from 2-Hydroxyacetophenone in commercially feasible and cost-effective fashion. In the commercial production of various organic compounds it is useful to have flexible systems which can be tailored to production needs at any given time. In production of pharmaceutical materials it is highly desirable to have systems and production protocols which provide clean manufacturing and do not provide multiple transfers and cleaning steps during which contaminants may be introduced. As the background demonstrates numerous others have provided means or syntheses, usually including multiple steps, for reaching a single compound at a single endpoint. Web site: http://www.delphion.com/details?pn=US05696274__
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Weather resistant, sweet corn-based rodenticidal bait and method of manufacturing same Inventor(s): Eades; Ed (Middleton, WI), Lush; Raymon W. (Bloomfield, NE), Schwalenberg; Lee D. (Waterloo, WI) Assignee(s): HACCO, Inc. (Randolph, WI), Sweet Corn Products Co. (Bloomfield, NE) Patent Number: 5,876,740 Date filed: August 7, 1997 Abstract: A weather resistant, rodenticidal bait comprises sweet corn flour, an effective amount of a rodenticide, and water. Additional preferred ingredients include a glutinous flour, flavoring and salt. Preferred rodenticides include diphacinone, brodifacoum, warfarin, bromadialone, bromethalin and their functional equivalents. A preferred method of manufacturing the weather resistant rodenticidal bait of the present invention utilizes cold extrusion techniques. The most preferred method of
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manufacturing includes the steps of mixing a sweet corn flour, an effective amount of a rodenticide, and water to produce a rodenticidal mixture. In the preferred method, a glutinous flour is also mixed with the sweet corn flour, with wheat flour the most preferred glutinous flour. The rodenticidal mixture is forced through an extrusion chamber and out a nozzle opening, to produce extruded chunks. The extruded chunks are preferably dried to obtain weather resistant, sweet corn-based rodenticidal bait having a sweet corn content of at least 65% by weight of the weather resistant bait and a moisture content of not more than 10% by weight of the weather resistant bait. Excerpt(s): The present invention relates to rodenticidal bait compositions. More particularly, the present invention relates to weather resistant, rodenticidal bait compositions having satisfactory rodent acceptability and to methods of manufacturing same. Rodenticidal baits typically include a carrier and a rodenticide. The rodenticide is the active ingredient and the carrier is often referred to as an inert ingredient. In most rodenticidal baits, the carrier is really not chemically inert, in that it typically contains one or more grains or other foods which are attractive to rodents. The carrier does not, however, typically contribute to the rodenticidal activity of the bait, and thus is inert in that respect. U.S. Pat. No. 4,815,923 for SWEET CORN BASED RODENTICIDE to Raymon W. Lush issued Mar. 28, 1989 and discloses a rodenticidal bait which includes an active ingredient mixed with an inert ingredient comprising dried sweet corn as a substantial portion thereof. The '923 patent recites that the optimal particle size of the ground corn for such use with Norway and roof rats is between 0.5 mm and 1.5 mm in diameter. In addition, the '923 patent contemplates using ground sweet corn of this grind to form rodenticidal pellets of approximately 3/16 inch in diameter. Experience has shown that such pellets have an average bulk density of less than 45 lbs/ft.sup.3. Rodenticidal efficacy tests disclosed in the '923 patent indicated that when test rats were presented with such pellets and with a challenge bait containing 65% yellow dent corn, 25% rolled oats, 5% corn oil and 5% white sugar but no active ingredient, the pellets containing an active ingredient constituted over one half of the rats' diet and resulted in a 100% mortality rate. Web site: http://www.delphion.com/details?pn=US05876740__
Patent Applications on Warfarin As of December 2000, U.S. patent applications are open to public viewing.10 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to warfarin: •
Enhancing the toxicity of warfarin in rodents Inventor(s): Poche, Richard M.; (Wellington, CO) Correspondence: Frederick H. Rabin; Fish & Richardson P.C.; Suite 2800; 45 Rockefeller Plaza; New York; NY; 10111; US Patent Application Number: 20010041737 Date filed: June 18, 2001
10
This has been a common practice outside the United States prior to December 2000.
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Abstract: The presence of a small amount of an antibiotic, such as metronidazole or a salt or derivative thereof, in warfarin-containing rodent baits enhances the toxicity of warfarin against rodents which have heretofore shown apparent resistance to warfarin. Excerpt(s): This invention relates to methods for enhancing the toxicity of warfarin in rodenticidal compositions and to warfarin-containing rodenticidal compositions which are effective against warfarin-resistant rodents. has, since the 1950s been in use as an active ingredient in rodenticidal compositions. In addition to its use as a rodenticide, warfarin is also used, in generally smaller amounts, in humans to provide similar anticoagulating effects. The basis for the effectiveness of warfarin as a rodenticide lies in the fact that it is effective in small, multiple doses. One or two doses of the compound are seldom fatal if taken at the recommended concentration; thus the hazard of acute toxicity to man, domestic animals, and wildlife is greatly reduced. In practical use, warfarin has been sold as a "concentrate" containing 0.5 percent of the active ingredient. This is diluted for use with a suitable bait, to a concentration of about 0.025 percent. Baits commonly used are cereal products, corn meal, rolled oats, mixed animal feeds, and similar products. Baits containing warfarin can be placed in stations and left there for considerable periods of time, so that the rodent populations may partake of several doses in sequence. Usually the rodents begin to die after four or five daily doses of the materials, and the population is greatly reduced or eradicated in approximately three weeks. Death is caused by hemorrhages, brought about by the action of the warfarin in reducing the clotting power of the blood. These hemorrhages may be external or internal and can be initiated by very slight injury or capillary damage. One of the other advantages of warfarin is that, because multiple ingestions are required to kill the rodents, they do not develop bait shyness. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Materials and methods for treating coagulation disorders Inventor(s): Druzgala, Pascal; (Santa Rosa, CA), Pfister, Jurg; (Los Altos, CA), Zhang, Xiaoming; (Campbell, CA) Correspondence: Saliwanchik Lloyd & Saliwanchik; A Professional Association; 2421 N.W. 41st Street; Suite A-1; Gainesville; FL; 326066669 Patent Application Number: 20030199573 Date filed: April 24, 2002 Abstract: This invention is drawn to compounds which are more easily metabolized by the metabolic drug detoxification systems. Particularly, warfarin analogs which have been designed to include esters within the structure of the compounds are taught. The invention teaches methods of reducing the toxicity of drugs comprising the introduction of ester groups into drugs during the synthesis of the drug. This invention is also drawn to methods of treating coagulation disorders comprising the administration of compounds which have been designed to be metabolized by serum or intracellular hydrolases and esterases. Pharmaceutical compositions of the ester containing warfarin, analogs are also taught. Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/286,079, filed Apr. 24, 2001. Warfarin (coumarin) is an anticoagulant which acts by inhibiting vitamin K-dependent coagulation factors. Warfarin based compounds are, typically, derivatives of 4-hydroxycoumarin, such as 3-(a-acetonylbenzyl)-4hydroxycoumarin (COUMADIN). COUMADIN and other coumarin anticoagulants
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inhibit the synthesis of vitamin K dependent clotting factors, which include Factors II, VII, IX and X. Anticoagulant proteins C and S are also inhibited by warfarin anticoagulants. Warfarin is believed to interfere with clotting factor synthesis by inhibiting vitamin K.sub.1 epoxide regeneration. An anticoagulation effect is generally seen about 24 hours after administration and single doses of warfarin are effective for 2 to 5 days. While anticoagulants have no direct effect on an established thrombus and do not reverse ischemic tissue damage, anticoagulant treatment is intended to prevent the extension of formed clots and/or to prevent secondary thromboembolic complications. These complications may result in serious and possibly fatal sequelae. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Method and system for administering anticoagulation therapy Inventor(s): Wurster, Mark; (Parkville, MO) Correspondence: Darby & Darby P.C.; Post Office Box 5257; New York; NY; 10150-5257; US Patent Application Number: 20020116222 Date filed: October 22, 2001 Abstract: A method and system for effectively administering anticoagulation therapy, including providing a warfarin dose weekly schedule and converting a total weekly requirement into daily dosages based on the number of milligrams in the pills selected for treatment. A default pill size can be selected as well as other customizable features. Medications can be recorded simultaneously and potential drug interactions are highlighted. Dates on which the patient should return to the clinic are automatically calculated for review. The patient is provided with a hardcopy of the visit as well as the recommended warfarin dose schedule. The user is provided with several customizable options for recording pertinent visit data. Excerpt(s): The present application claims the benefit of U.S. Provisional Application No. 60/242,576, filed Oct. 22, 2000, which is herein incorporated by reference in its entirety. The present invention relates to the field of health care management, and in particular to a system and method for the administration of anticoagulation therapy. Anticoagulation therapy refers to the use of medications in patients at risk with the goal of preventing abnormal clotting of the blood. This type of therapy can be applied in a wide variety of medical disorders and patient populations. Such therapy may take a number of forms, which vary in terms of medication(s) utilized, duration of therapy, setting in which the treatment is administered and potential side effects. When used effectively, anticoagulation therapy can be potentially life saving and has been repeatedly shown to decrease patient suffering and the overall cost of health care. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Method for detecting procoagulant genetic and metabolic conditions associated with, and potentially predispositional for, activation of the coagulation response Inventor(s): Berg, David E.; (Phoenix, AZ), Berg, Lois Hill; (Phoenix, AZ), Harrison, Harold H.; (Scottsdale, AZ) Correspondence: Charles E. Cates; Cates & Holloway; P.O. Box 1532; Scottsdale; AZ; 85252-1532; US Patent Application Number: 20020037528 Date filed: September 28, 2001 Abstract: Methods for diagnosing and identifying genetic and metabolic factors associated with a physiologic procoagulant predisposition for and concurrent activation of the coagulation response in patients suffering from conditions such as chronic fatigue syndrome, fibromyalgia, Gulf War illness and cardiovascular disease are disclosed. Diagnostic assays utilized in the methods include measurement of blood levels of Protein C, Protein S, antithrombin, activated protein C resistance, prothrombin plasminogen activator inhibitor-1, lipoprotein (a) and homocysteine. Treatment regimens include anticoagulant therapies comprising administering warfarin or heparin as needed. Excerpt(s): This Non-Provisional Application claims the benefit of co-pending, U.S. Non-Provisional Application Ser. No. 09/637,808, filed Aug. 11, 2000 which in turn claims the benefit of Provisional Application No. 60/148,799, filed Aug. 13, 1999. This invention relates to methods for diagnosing and identifying genetic and metabolic procoagulant factors associated with predisposition for and/or concurrent activation of the coagulation response which may respond to anti-coagulant therapy. For the purpose of this filing the term procoagulant factor refers to an abnormal result in the group of tests which presently includes: Protein C, Protein S, antithrombin, activated protein C resistance, prothrombin, plasminogen activator inhibitor-1, lipoprotein (a) and homocysteine. Chronic fatigue syndrome (CFS), fibromyalgia (FM), Gulf War Illness (GWI) and related chronic illnesses have been considered diagnoses of exclusion where no other diagnosis fits well. CFS has been defined by specific requirements of fatigue, its duration, associated symptoms, and initial clinical and laboratory evaluation. There has existed no reliable laboratory means for determining whether an individual was suffering from CFS, FM, or some other disease. Gulf War illness and CFS share many clinical characteristics and may be variations of similar underlying pathophysiology. Accordingly, a felt need for a method of testing for CFS, FM, and related illnesses, such as GWI, existed. We have previously demonstrated low level activation of coagulation in many of these patients by measurement of blood levels of fibrinogen, prothrombin fragment 1+2, thrombin-antithrombin complexes, soluble fibrin monomer, and platelet CD62P activation. We have now conducted analyses of underlying genetic and metabolic factors that could contribute to a predisposition to develop such illnesses or yield a more enhanced activation of coagulation in patients who acquire the illnesses. These new tests include Protein C, Protein S, antithrombin, activated protein C resistance, prothrombin activity, plasminogen activator inhibitor-1, lipoprotein (a) and homocysteine. Various methods including protein, enzymatic activity, amino acid analysis and analysis of gene sequences apply to these genetic and metabolic procoagulant markers. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Method of controlling zoological and aquatic plant growth Inventor(s): Cutler, Horace G.; (Watkinsville, GA), Cutler, Stephen J.; (Roswell, GA), Dawson, Rodger; (Owings, MD), Wright, David; (Solomon, MD) Correspondence: Roylance, Abrams, Berdo & Goodman, L.L.P.; 1300 19th Street, N.W.; Suite 600; Washington,; DC; 20036; US Patent Application Number: 20020098979 Date filed: December 6, 2001 Abstract: A method of controlling target aquatic microorganism pest populations by exposing the target population to an effective amount of an aquacidal compound. The aquacidal compounds are selected from the group consisting of quinones, anthraquinones, naphthalenediones, quinine, warfarin, coumarins, amphotalide, cyclohexadiene-1,4-dione, phenidione, pirdone, sodium rhodizonate, apirulosin and thymoquinone. The method is particularly effective for treating ballast water of ships or other enclosed volumes of water subject to transport between or among geographic areas to control the relocation of plants, toxic bacteria, and animals contained in the water. Excerpt(s): This application is based on PCT application PCT/US01/05117 which is a continuation-in-part of copending U.S. patent application Ser. No. 09/506,017 that was filed on Feb. 17, 2000 and U.S. provisional patent application serial No. 60/237,401 that was filed on Oct. 4, 2000. The disclosures of these applications are incorporated herein by reference. The present invention is directed to a method and compositions for controlling aquatic pests, including zoological organisms and plants. More specifically, the invention is directed to a method and composition for controlling, inhibiting, and terminating populations of aquatic and marine pest plants, organisms, and animals in a target treatment zone. The invention is particularly applicable for sterilizing a treated water volume (whether or not enclosed) of mollusks, dinoflagellates, bacteria and algae. The discovery in the Summer of 1988 of the Eurasian zebra mussel Dressiness polymorph in the Great Lakes of North America represents one of the most significant events in the history of aquatic biological invasion. However, this was not the first event of a non-indigenous species entering into US water. Earlier, the spiny water flea Bythotrephes cedarstroemi and the ruffe Gymnocephalus cernuus had entered the United States from ballast water of European ports. It was soon discovered that zebra mussel had also entered the US via ballast water of European origin. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Preparation of warfarin sodium from warfarin sodium-2-propanol clathrate Inventor(s): Bercovici, Sorin; (Kiriatono, IL), Chernyak, Shimon; (Yokneam Ilit, IL), Ulanenko, Konstantin; (Natania, IL) Correspondence: Venable; Post Office Box 34385; Washington; DC; 20043-9998; US Patent Application Number: 20020120156 Date filed: February 28, 2001 Abstract: The present invention is a method for producing warfarin sodium from warfarin sodium 2-propanol clathrate by thermal, nondestructive solvent expulsion. The solvent expulsion is conducted under conditions of controlled heat transfer whereby the 2-propanol is expelled from the warfarin sodium 2-propanol clathrate
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without decomposition of warfarin sodium or the clathrate. Heating is conducted the clathrate at a temperature from about 100.degree. C. to about 170.degree. C. in an active oven under air or in an inert atmosphere and at partial pressures ranging from that of a relative vacuum to atmospheric pressure. The invention also relates to pure warfarin sodium prepared according to the method of the invention and pharmaceutical compositions containing warfarin sodium. Excerpt(s): The present invention relates to a process for preparation of warfarin sodium. More specifically, the present invention relates to a process for preparing warfarin sodium from warfarin sodium 2-propanol clathrate by solvent expulsion. According to U.S. Pat. No. 3,192,232, warfarin sodium prepared by existing methods often has as undesirable slight yellow color. (See also, U.S. Pat. No. 3,077,481). U.S. Pat. No. 3,246,013 also emphasizes the difficulties encountered with the preparation of a high purity warfarin sodium. This patent discloses that the removal of the 2-propanol solvent from warfarin sodium 2-propanol clathrate cannot be achieved even with heating at 100.degree. C. over P.sub.2O.sub.5 for 3-5 hours in a high vacuum (0.1 mm Hg). U.S. Pat. No. 3,077,481 further discloses that heating the clathrate at higher temperatures (145.degree. C.) in air at a high vacuum (1.0 mm Hg) for prolonged time periods (24 hours) results in undesirable decomposition. Also, heating at still higher temperatures (230.degree. C.), while successfully removing 2-propanol from the clathrate, results in rapid decomposition. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
PROCESS FOR SYNTHESIS OF PURE WARFARIN ACID, WARFARIN ALKALI METAL SALTS AND CORRESPONDING CLATHRATES Inventor(s): Bercovici, Sorin; (Kiriat Ono, IL), Evron, Yuval; (Lower Galilee, IL), Fuxman, Osvaldo; (Haifa, IL), Jakoel, Mirela; (Kiriat Motzkin, IL), Sasson, Sbar; (Rehovot, IL), Ulanenko, Konstantin; (Natania, IL) Correspondence: Venable; Post Office Box 34385; Washington; DC; 20043-9998; US Patent Application Number: 20020120155 Date filed: February 28, 2001 Abstract: An improved procedure for the purification of warfarin acid. Sodium, potassium and lithium warfarin salts and the corresponding clathrates are prepared in high, pharmacopeial grade purity and good yields from the pure warfarin acid and the respective metal salt bases in suitable media. Excerpt(s): The invention relates to a synthesis of pure warfarin acid and derivatives thereof. In particular, the invention relates to a commercially feasible, large scale process for purification of warfarin acid in high, pharmacopoeial grades of purity. Warfarin sodium, warfarin sodium 2-propanol clathrate, warfarin potassium and warfarin lithium 2-propanol clathrate are highly potent anticoagulants, generally administered orally and used extensively as active pharmaceutical ingredients (APIs). These compounds are also widely used as rodenticides in different dosages and formulations. The commercial production of APIs preferably uses systems and processes capable of providing high quality, pure intermediates and products complying with pharmacopoeial requirements. Numerous procedures for the synthesis of warfarin acid, its salts and clathrates exist, but there is still a need by the pharmaceutical industry for methods of preparing these compounds in high quality as both intermediates and products and particularly for the preparation of high purity warfarin acid.
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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 warfarin, 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 “warfarin” (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 warfarin. You can also use this procedure to view pending patent applications concerning warfarin. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.
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CHAPTER 7. BOOKS ON WARFARIN Overview This chapter provides bibliographic book references relating to warfarin. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on warfarin 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 “warfarin” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “warfarin” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “warfarin” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •
The New Dimensions of Warfarin Prophylaxis (Advances in Experimental Medicine and Biology, 214) by Carl Becker, Stanford, Nemerson, Yale Wessler (Editor); ISBN: 0306425882; http://www.amazon.com/exec/obidos/ASIN/0306425882/icongroupinterna
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Warfarin Health and Safety Guide (Health and Safety Guide: 96) (1995); ISBN: 924151096X; http://www.amazon.com/exec/obidos/ASIN/924151096X/icongroupinterna
The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search
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area, simply type “warfarin” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:11 •
Cost-effectiveness of enoxaparin versus warfarin for prevention of deep vein thrombosis following total hip replacement Author: O'Brien, B.; Year: 1993; Ontario: CHEPA, 1993
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Studies on chemical determination of warfarin and coumachlor and their toxicity for dog and swine. Author: Wanntorp, Hans.; Year: 1960; Copenhagen, Munksgaard, 1960
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Studies on the absorption and distribution pharmacokinetics of warfarin in the rat Author: Julkunen, Risto.; Year: 1977; Helsinki: [s.n.], 1977
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The use of meta-analysis in a technology assessment: warfarin for stroke prevention in atrial fibrillation Author: Green, C. J.; Year: 1997; Vancouver, British Columbia, Canada: BCOHTA CHSPR, 1997
Chapters on Warfarin In order to find chapters that specifically relate to warfarin, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and warfarin 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 “warfarin” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on warfarin: •
Oral Medicine Source: in Sonis, S.T., ed. Dental Secrets: Questions You Will Be Asked On Rounds, In the Clinic, On Exams, On Boards. Philadelphia, PA: Hanley and Belfus, Inc. 1994. p. 1732. Contact: Available from Hanley and Belfus, Inc. Medical Publishers, 210 South 13th Street, Philadelphia, PA 19107. (800) 962-1892 or (215) 546-7293; Fax (215) 790-9330; http://www.hanleyandbelfus.com. PRICE: $36.95 plus shipping and handling. ISBN: 1560530634. Summary: Presented in a question and answer format, this book chapter on oral medicine is from a mini-textbook that can be used as a review for examinations, rounds, and clinical discussions. Topics covered include disorders of hemostasis, including patient indications for surgery, gingival bleeding, and the use of warfarin; indications for prophylactic antibiotics, including the specific antibiotics and dosages recommended by the American Heart Association; treatment of HIV-positive patients; cardiovascular
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In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is currently adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a "Books" button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.
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disease, including the emergency management of a possible cardiovascular event; metabolic disorders, including diabetes mellitus, patients on corticosteroids, and hypothyroidism; allergic reactions, including the symptoms of anaphylaxis; hematology and oncology, including sickle cell anemia, leukemia, chemotherapy, and radiation therapy; kidney disease, including patients on dialysis and patients with kidney transplants; pulmonary disease; liver disease; and seizures. This book chapter provides specific management strategies, including the recommended drug administration and dosages. 3 tables. 16 references.
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CHAPTER 8. PERIODICALS AND NEWS ON WARFARIN Overview In this chapter, we suggest a number of news sources and present various periodicals that cover warfarin.
News Services and Press Releases One of the simplest ways of tracking press releases on warfarin 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 “warfarin” (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 warfarin. 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 “warfarin” (or synonyms). The following was recently listed in this archive for warfarin: •
Warfarin safely prevents ischemic stroke in elderly patients with atrial fibrillation Source: Reuters Industry Breifing Date: November 25, 2003
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Ximelagatran equal to warfarin in stroke prevention in patients with AF Source: Reuters Medical News Date: November 11, 2003
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Patients on warfarin advised against drinking cranberry juice Source: Reuters Industry Breifing Date: September 18, 2003
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Experts warn warfarin users about cranberry juice Source: Reuters Health eLine Date: September 18, 2003
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Standard warfarin therapy best for long-term prevention of recurrent thrombosis Source: Reuters Medical News Date: August 13, 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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Exanta tops warfarin for patients with atrial fibrillation Source: Reuters Industry Breifing Date: April 03, 2003
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Concomitant warfarin and fluorouracil treatment increases risk of bleeding Source: Reuters Industry Breifing Date: March 12, 2003
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Long-term, low-dose warfarin safely lowers risk of recurrent thrombotic embolism Source: Reuters Industry Breifing Date: February 24, 2003
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Ximelagatran outperforms warfarin as antithrombotic agent after knee surgery Source: Reuters Medical News Date: December 09, 2002
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AstraZeneca's Exanta outperforms warfarin for antithrombosis after knee surgery Source: Reuters Industry Breifing Date: December 09, 2002
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Warfarin-induced skin necrosis reported in hemodialysis patient Source: Reuters Industry Breifing Date: December 04, 2002
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Extended warfarin therapy may reduce thrombotic risks after hip surgery Source: Reuters Industry Breifing Date: October 03, 2002
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Warfarin better than aspirin alone after acute myocardial infarction Source: Reuters Industry Breifing Date: September 25, 2002
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Warfarin therapy may modify underlying pathology of angina Source: Reuters Industry Breifing Date: April 30, 2002
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Herbal supplement for prostate cancer contains indomethacin, DES and warfarin Source: Reuters Industry Breifing Date: April 10, 2002
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Low-dose warfarin and aspirin no more effective than aspirin alone after AMI Source: Reuters Industry Breifing Date: February 04, 2002
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Many physicians do not prescribe warfarin for AF patients Source: Reuters Industry Breifing Date: November 21, 2001
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Aspirin equal to warfarin for stroke prevention Source: Reuters Health eLine Date: November 14, 2001
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Aspirin and warfarin equivalent for prevention of recurrent ischemic stroke Source: Reuters Industry Breifing Date: November 14, 2001
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Warfarin underused in atrial fibrillation patients in long-term care Source: Reuters Medical News Date: November 12, 2001
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Adding warfarin to aspirin improves secondary prevention post-MI Source: Reuters Medical News Date: September 03, 2001
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DuPont reaches $44.5 million preliminary settlement for Coumadin suits Source: Reuters Industry Breifing Date: August 07, 2001
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Withholding warfarin safe for prosthetic heart valve patients with major bleeding Source: Reuters Industry Breifing Date: March 09, 2001
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FDA warns of OTC vaginal drugs, warfarin health risk Source: Reuters Industry Breifing Date: March 06, 2001
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FDA warns about warfarin, miconazole interaction Source: Reuters Medical News Date: March 06, 2001
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Pneumatic compression and warfarin reduce thrombosis risk after hip replacement Source: Reuters Medical News Date: December 14, 2000
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Warfarin underprescribed to cancer patients with central venous catheters Source: Reuters Medical News Date: November 29, 2000
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Education helps prevent major bleeding in older patients taking warfarin Source: Reuters Medical News Date: November 06, 2000
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Vitamin K reduces blood-clotting time in patients on warfarin Source: Reuters Medical News Date: November 03, 2000
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Cerebral amyloid angiopathy linked to warfarin-related hemorrhage in elderly Source: Reuters Industry Breifing Date: October 13, 2000
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Patient on warfarin develops hypoprothrombinemia during celecoxib therapy Source: Reuters Industry Breifing Date: October 03, 2000
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Low-intensity warfarin effective in preventing coronary events in high-risk me Source: Reuters Medical News Date: September 15, 2000 The NIH
Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “warfarin” (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 “warfarin” (or synonyms). If you know the name of a company that is relevant to warfarin, 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 “warfarin” (or synonyms).
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Newsletter Articles Use the Combined Health Information Database, and limit your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter Article.” Type “warfarin” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months. The following is a typical result when searching for newsletter articles on warfarin: •
Acid Blockers: How You Can Head Off Heartburn Before It Starts Source: Mayo Clinic Health Letter. 15(11): 7. November 1997. Contact: Available from Mayo Clinic Health Letter. Subscription Services, P.O. Box 53889, Boulder, CO 80322-3889. (800) 333-9037 or (303) 604-1465. Summary: This brief article from a health newsletter reviews the use of acid blockers or H2 blockers. These drugs have recently become available over the counter (OTC) and can be labelled as acid blockers, acid reducers, or acid controllers. The article explores the use of these medications for treating mild to moderate heartburn, the causes of heartburn, and how OTC acid blockers work. Heartburn results from gastroesophageal reflux, a condition in which stomach acids back up (reflux) into the esophagus. The result is a burning pain behind the breastbone, often accompanied by a sour taste and the sensation of food coming back into the mouth. OTC acid blockers work by blocking the effects of histamine, a chemical that signals the stomach cells to produce acid. Acid blockers differ from traditional antacids in that they can prevent heartburn, not just relieve it. The author reviews possible drug interaction problems (notably Tagamet HB with the asthma drug theophylline, the blood thinner warfarin, or the seizure drug phenytoin). The article stresses that the best way to control heartburn is to determine and avoid what is triggering the attacks. OTC acid blockers and antacids can be helpful for occasional bouts of heartburn, but they aren't meant for severe symptoms or to be taken daily or several times a week. 2 figures. (AA-M).
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Antiphospholipid Syndrome: What We Know Today and What the Future Holds Source: Lupus News. 20(5): 14-16. Winter 2000. Contact: Available from Lupus Foundation of America. 1300 Piccard Drive, Suite 200, Rockville, MD 20850-4303. (800) 558-0121 or (301) 670-9292. Fax (301) 670-9486. Website: www.lupus.org/lupus. Summary: This newsletter article provides people who have lupus with information on the antiphospholipid syndrome (APLS). This blood clotting disorder affects many people who have lupus. People who have APLS develop antibodies to structures in the membranes of cells that line the bloodstream, and these antibodies, known as antiphospholipid (APL) antibodies, interfere with important blood clotting proteins. The article reviews some historical findings that may help explain APLS, including the finding in the 1940s that women with lupus were testing positive for syphilis, the finding in 1948 that some patients with lupus with blood clotting problems had a particular antibody in their blood that increased clotting time in a test tube, and the identification in the 1980s of several antiphospholipid antibodies. There are several tests available to help diagnose APLS, including several versions of the lupus anticoagulant
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test, tests that directly measure antibodies to phospholipids or associated blood clotting proteins, and a test that measures antibodies to beta-2 glucoprotein 1. Several kinds of therapies are used to prevent future clots once a person has been diagnosed with the APLS, including avoiding the use of medications that may increase blood clotting risk and taking extra precautions in situations that may provoke blood clotting. People who have tested positive for lupus anticoagulant or anticardiolipin antibody but have never had a blood clot may be prescribed one aspirin per day. People who have experienced a blood clot traditionally have been prescribed warfarin, but use of this medication can be problematic because of its drug and food interactions. Although new drugs are in development for APLS and alternative therapies are available, there are significant impediments to research on the disorder. 1 table.
Academic Periodicals covering Warfarin Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to warfarin. In addition to these sources, you can search for articles covering warfarin that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”
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CHAPTER 9. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.
U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for warfarin. 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 nonprofit 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 warfarin. 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 warfarin: Anticoagulants •
Systemic - U.S. Brands: Coumadin; Miradon http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202050.html
Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.
Mosby’s Drug Consult Mosby’s Drug Consult database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/. PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee.
Researching Orphan Drugs Although the list of orphan drugs is revised on a daily basis, you can quickly research orphan drugs that might be applicable to warfarin by using the database managed by the National Organization for Rare Disorders, Inc. (NORD), at http://www.rarediseases.org/. Scroll down the page, and on the left toolbar, click on “Orphan Drug Designation Database.” On this page (http://www.rarediseases.org/search/noddsearch.html), type “warfarin” (or synonyms) into the search box, and click “Submit Query.” When you receive your results, note that not all of the drugs may be relevant, as some may have been withdrawn from orphan status. Write down or print out the name of each drug and the relevant contact information. From there, visit the Pharmacopeia Web site and type the name of each orphan
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drug into the search box at http://www.nlm.nih.gov/medlineplus/druginformation.html. You may need to contact the sponsor or NORD for further information. NORD conducts “early access programs for investigational new drugs (IND) under the Food and Drug Administration’s (FDA’s) approval ‘Treatment INDs’ programs which allow for a limited number of individuals to receive investigational drugs before FDA marketing approval.” If the orphan product about which you are seeking information is approved for marketing, information on side effects can be found on the product’s label. If the product is not approved, you may need to contact the sponsor. The following is a list of orphan drugs currently listed in the NORD Orphan Drug Designation Database for warfarin: •
Protein C concentrate (trade name: Protein C Concentrate (human) Vapor Heated (Immuno)) http://www.rarediseases.org/nord/search/nodd_full?code=433
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 Institute12: •
Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm
•
National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/
•
National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html
•
National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25
•
National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm
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National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm
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National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375
•
National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/
12
These publications are typically written by one or more of the various NIH Institutes.
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•
National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm
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National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/
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National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm
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National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm
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National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/
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National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/
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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm
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National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html
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National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm
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National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm
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National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm
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National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html
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National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm
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Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp
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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
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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.13 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:14 •
Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html
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HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html
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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/
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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
13
Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 14 See http://www.nlm.nih.gov/databases/databases.html.
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Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html
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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 Gateway15 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.16 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “warfarin” (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 10152 50 1005 26 9 11242
HSTAT17 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.18 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.19 Simply search by “warfarin” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
15
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
16
The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 17 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 18 19
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 Biologists20 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.21 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.22 This site has new articles 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/.
20 Adapted 21
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. 22 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each 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 warfarin 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 warfarin. 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 warfarin. 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 “warfarin”:
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Other guides Bleeding Disorders http://www.nlm.nih.gov/medlineplus/bleedingdisorders.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 warfarin. 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: •
Antibiotics Source: Canadian Journal of Gastroenterology. 12(6): 390-391. September 1998. Contact: Available from Pulsus Group, Inc. 2902 South Sheridan Way, Oakville, Ontario, Canada L6J 7L6. (905) 829-4770. Fax (905) 829-4799. E-mail:
[email protected]. Summary: This fact sheet for patients is printed in a physician's gastroenterology journal and summarizes the use of antibiotics in bowel disease, including potential side effects. Antibiotics are not first line therapy for inflammatory bowel disease (IBD) but are often given in addition to other medications, particularly for Crohn's disease. They are most often used to treat perineal disease (abscesses and fistulas in the perineum). However, antibiotics may also be useful in fighting disease in other parts of the intestine and helping prevent recurrence after surgery for Crohn's disease. The most commonly prescribed antibiotics for IBD are metronidazole and ciprofloxacin. Some of the more common side effects of metronidazole are nausea, diarrhea, abdominal pain, metallic taste, and a sore tongue. Metronidazole may increase the effects of other drugs as well, particularly lithium and warfarin. The most frequent side effects of ciprofloxacin are
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nausea, vomiting, skin rash, diarrhea, and headache. Also, ciprofloxacin may increase the effects of theophylline and caffeine. Both metronidazole and ciprofloxacin have the potential to cause oral thrush (fungal infection of the mouth). The fact sheet concludes that, although it seems as if there are a number of side effects, most patients do well on these drugs and have no problems. 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 warfarin. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/specific.htm
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Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/
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Med Help International: http://www.medhelp.org/HealthTopics/A.html
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Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/
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Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/
•
WebMDHealth: http://my.webmd.com/health_topics
Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to warfarin. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with warfarin. 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 warfarin. 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.
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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 “warfarin” (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 “warfarin”. 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 “warfarin” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “warfarin” (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.23
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
23
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)24: •
Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/
•
Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)
•
Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm
•
California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html
•
California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html
•
California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html
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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
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California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/
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California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/
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California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/
•
California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html
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California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/
•
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/
24
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
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Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm
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Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html
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Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm
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Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp
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Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/
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Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm
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Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html
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Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/
•
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/
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Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm
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Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html
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Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm
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Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/
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Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/
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Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10
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Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/
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Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html
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Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp
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Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp
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Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/
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Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html
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Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm
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Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp
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Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/
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Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html
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Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/
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Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm
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Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/
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Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html
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Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm
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Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330
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Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)
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National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html
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National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/
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National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/
Finding Medical Libraries
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Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm
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New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/
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New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm
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New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm
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New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/
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New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html
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New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/
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New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html
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New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/
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Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm
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Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp
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Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/
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Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/
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Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml
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Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html
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Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html
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Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml
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Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp
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Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm
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Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/
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South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp
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Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/
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Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/
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Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72
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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •
ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html
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MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp
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Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/
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Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html
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On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/
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Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp
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Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm
Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a).
Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •
Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical
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MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html
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Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/
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Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine
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WARFARIN DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 2-Propanol: An isomer of 1-propanol. It is a colorless liquid having disinfectant properties. It is used in the manufacture of acetone and its derivatives and as a solvent. Topically, it is used as an antiseptic. [NIH] Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Abscess: Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. [NIH] Absolute risk: The observed or calculated probability of an event in a population under study, as contrasted with the relative risk. [NIH] ACE: Angiotensin-coverting enzyme. A drug used to decrease pressure inside blood vessels. [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] Acetone: A colorless liquid used as a solvent and an antiseptic. It is one of the ketone bodies produced during ketoacidosis. [NIH] Acidosis: A pathologic condition resulting from accumulation of acid or depletion of the alkaline reserve (bicarbonate content) in the blood and body tissues, and characterized by an increase in hydrogen ion concentration. [EU] Acute leukemia: A rapidly progressing cancer of the blood-forming tissue (bone marrow). [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] Adamantane: A tricyclo bridged hydrocarbon. [NIH] Adenocarcinoma: A malignant epithelial tumor with a glandular organization. [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] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH]
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Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adverse Effect: An unwanted side effect of treatment. [NIH] 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] Afterload: The tension produced by the heart muscle after contraction. [EU] 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]
Agarose: A polysaccharide complex, free of nitrogen and prepared from agar-agar which is produced by certain seaweeds (red algae). It dissolves in warm water to form a viscid solution. [NIH] Age-Adjusted: Summary measures of rates of morbidity or mortality in a population using statistical procedures to remove the effect of age differences in populations that are being compared. Age is probably the most important and the most common variable in determining the risk of morbidity and mortality. [NIH] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] Alertness: A state of readiness to detect and respond to certain specified small changes occurring at random intervals in the environment. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH]
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Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alprenolol: 1-((1-Methylethyl)amino)-3-(2-(2-propenyl)phenoxy)-2-propanol. Adrenergic beta-blocker used as an antihypertensive, anti-anginal, and anti-arrhythmic agent. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Alveolar Process: The thickest and spongiest part of the maxilla and mandible hollowed out into deep cavities for the teeth. [NIH] Alveoli: Tiny air sacs at the end of the bronchioles in the lungs. [NIH] Amebiasis: Infection with any of various amebae. It is an asymptomatic carrier state in most individuals, but diseases ranging from chronic, mild diarrhea to fulminant dysentery may occur. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amiodarone: An antianginal and antiarrhythmic drug. It increases the duration of ventricular and atrial muscle action by inhibiting Na,K-activated myocardial adenosine triphosphatase. There is a resulting decrease in heart rate and in vascular resistance. [NIH] Amoxicillin: A broad-spectrum semisynthetic antibiotic similar to ampicillin except that its resistance to gastric acid permits higher serum levels with oral administration. [NIH] Ampicillin: Semi-synthetic derivative of penicillin that functions as an orally active broadspectrum antibiotic. [NIH] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH] Amyloid: A general term for a variety of different proteins that accumulate as extracellular fibrils of 7-10 nm and have common structural features, including a beta-pleated sheet conformation and the ability to bind such dyes as Congo red and thioflavine (Kandel, Schwartz, and Jessel, Principles of Neural Science, 3rd ed). [NIH]
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Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Analytes: A component of a test sample the presence of which has to be demonstrated. The term "analyte" includes where appropriate formed from the analyte during the analyses. [NIH]
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] Anaphylaxis: An acute hypersensitivity reaction due to exposure to a previously encountered antigen. The reaction may include rapidly progressing urticaria, respiratory distress, vascular collapse, systemic shock, and death. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Androgens: A class of sex hormones associated with the development and maintenance of the secondary male sex characteristics, sperm induction, and sexual differentiation. In addition to increasing virility and libido, they also increase nitrogen and water retention and stimulate skeletal growth. [NIH] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] 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] Angina: Chest pain that originates in the heart. [NIH] Angina Pectoris: The symptom of paroxysmal pain consequent to myocardial ischemia usually of distinctive character, location and radiation, and provoked by a transient stressful situation during which the oxygen requirements of the myocardium exceed the capacity of the coronary circulation to supply it. [NIH] Angiography: Radiography of blood vessels after injection of a contrast medium. [NIH] Angiopathy: Disease of the blood vessels (arteries, veins, and capillaries) that occurs when someone has diabetes for a long time. There are two types of angiopathy: macroangiopathy and microangiopathy. In macroangiopathy, fat and blood clots build up in the large blood vessels, stick to the vessel walls, and block the flow of blood. In microangiopathy, the walls of the smaller blood vessels become so thick and weak that they bleed, leak protein, and slow the flow of blood through the body. Then the cells, for example, the ones in the center of the eye, do not get enough blood and may be damaged. [NIH] 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.
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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 positive pole during electrolysis. [NIH] Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [NIH] 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] Anthraquinones: An anthracene ring which contains two ketone moieties in any position. Can be substituted in any position except on the ketone groups. [NIH] Antiallergic: Counteracting allergy or allergic conditions. [EU] Antianginal: Counteracting angina or anginal conditions. [EU] Antiarrhythmic: An agent that prevents or alleviates cardiac arrhythmia. [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] Anticonvulsants: Drugs used to prevent seizures or reduce their severity. [NIH] Antidiabetic: An agent that prevents or alleviates diabetes. [EU] Antidiabetic Agent: A substance that helps a person with diabetes control the level of glucose (sugar) in the blood so that the body works as it should. [NIH] Antifungal: Destructive to fungi, or suppressing their reproduction or growth; effective against fungal infections. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with
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specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Antihypertensive: An agent that reduces high blood pressure. [EU] Anti-infective: An agent that so acts. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antimetabolite: A chemical that is very similar to one required in a normal biochemical reaction in cells. Antimetabolites can stop or slow down the reaction. [NIH] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] 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] Antipruritic: Relieving or preventing itching. [EU] Antipyretic: An agent that relieves or reduces fever. Called also antifebrile, antithermic and febrifuge. [EU] Antiseptic: A substance that inhibits the growth and development of microorganisms without necessarily killing them. [EU] Antithrombotic: Preventing or interfering with the formation of thrombi; an agent that so acts. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Aorta: The main trunk of the systemic arteries. [NIH] Aortic Valve: The valve between the left ventricle and the ascending aorta which prevents backflow into the left ventricle. [NIH] 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
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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] Arachidonate 12-Lipoxygenase: An enzyme that catalyzes the oxidation of arachidonic acid to yield 12-hydroperoxyarachidonate (12-HPETE) which is itself rapidly converted by a peroxidase to 12-hydroxy-5,8,10,14-eicosatetraenoate (12-HETE). The 12-hydroperoxides are preferentially formed in platelets. EC 1.13.11.31. [NIH] Arachidonate 15-Lipoxygenase: An enzyme that catalyzes the oxidation of arachidonic acid to yield 15-hydroperoxyarachidonate (15-HPETE) which is rapidly converted to 15-hydroxy5,8,11,13-eicosatetraenoate (15-HETE). The 15-hydroperoxides are preferentially formed in neutrophils and lymphocytes. EC 1.13.11.33. [NIH] Arachidonate Lipoxygenases: Enzymes catalyzing the oxidation of arachidonic acid to hydroperoxyarachidonates (HPETES). These products are then rapidly converted by a peroxidase to hydroxyeicosatetraenoic acids (HETES). The positional specificity of the enzyme reaction varies from tissue to tissue. The final lipoxygenase pathway leads to the leukotrienes. EC 1.13.11.- . [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Arrhythmia: Any variation from the normal rhythm or rate of the heart beat. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteriosclerosis: Thickening and loss of elasticity of arterial walls. Atherosclerosis is the most common form of arteriosclerosis and involves lipid deposition and thickening of the intimal cell layers within arteries. Additional forms of arteriosclerosis involve calcification of the media of muscular arteries (Monkeberg medial calcific sclerosis) and thickening of the walls of small arteries or arterioles due to cell proliferation or hyaline deposition (arteriolosclerosis). [NIH] 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] Arthroplasty: Surgical reconstruction of a joint to relieve pain or restore motion. [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] Astringent: Causing contraction, usually locally after topical application. [EU] Asymptomatic: Having no signs or symptoms of disease. [NIH] Atenolol: A cardioselective beta-adrenergic blocker possessing properties and potency similar to propranolol, but without a negative inotropic effect. [NIH]
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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] Atmospheric Pressure: The pressure at any point in an atmosphere due solely to the weight of the atmospheric gases above the point concerned. [NIH] Atrial: Pertaining to an atrium. [EU] Atrial Fibrillation: Disorder of cardiac rhythm characterized by rapid, irregular atrial impulses and ineffective atrial contractions. [NIH] 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] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Autacoids: A chemically diverse group of substances produced by various tissues in the body that cause slow contraction of smooth muscle; they have other intense but varied pharmacologic activities. [NIH] Autodigestion: Autolysis; a condition found in disease of the stomach: the stomach wall is digested by the gastric juice. [NIH] Autosuggestion: Suggestion coming from the subject himself. [NIH] Axillary: Pertaining to the armpit area, including the lymph nodes that are located there. [NIH]
Axillary Artery: The continuation of the subclavian artery; it distributes over the upper limb, axilla, chest and shoulder. [NIH] Azotemia: An excess of urea or other nitrogenous compounds in the blood. [EU] Babesiosis: A group of tick-borne diseases of mammals including zoonoses in humans. They are caused by protozoans of the genus babesia, which parasitize erythrocytes, producing hemolysis. In the U.S., the organism's natural host is mice and transmission is by the deer tick ixodes scapularis. [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 Infections: Infections by bacteria, general or unspecified. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH] Bacteriuria: The presence of bacteria in the urine with or without consequent urinary tract infection. Since bacteriuria is a clinical entity, the term does not preclude the use of urine/microbiology for technical discussions on the isolation and segregation of bacteria in the urine. [NIH] Barbiturate: A drug with sedative and hypnotic effects. Barbiturates have been used as sedatives and anesthetics, and they have been used to treat the convulsions associated with
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epilepsy. [NIH] Barium: An element of the alkaline earth group of metals. It has an atomic symbol Ba, atomic number 56, and atomic weight 138. All of its acid-soluble salts are poisonous. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]
Benzbromarone: Uricosuric that acts by increasing uric acid clearance. It is used in the treatment of gout. [NIH] Benzene: Toxic, volatile, flammable liquid hydrocarbon biproduct of coal distillation. It is used as an industrial solvent in paints, varnishes, lacquer thinners, gasoline, etc. Benzene causes central nervous system damage acutely and bone marrow damage chronically and is carcinogenic. It was formerly used as parasiticide. [NIH] Beta-pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Biliary Tract: The gallbladder and its ducts. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Binding agent: A substance that makes a loose mixture stick together. For example, binding agents can be used to make solid pills from loose powders. [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] 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] Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alteration may be either non-
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synthetic (oxidation-reduction, hydrolysis) or synthetic (glucuronide formation, sulfate conjugation, acetylation, methylation). This also includes metabolic detoxication and clearance. [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] Body Fluids: Liquid components of living organisms. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone Resorption: Bone loss due to osteoclastic activity. [NIH] Bone scan: A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Brachial: All the nerves from the arm are ripped from the spinal cord. [NIH] Brachial 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] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]
Breakdown: A physical, metal, or nervous collapse. [NIH]
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Broad-spectrum: Effective against a wide range of microorganisms; said of an antibiotic. [EU] Bromine: A halogen with the atomic symbol Br, atomic number 36, and atomic weight 79.904. It is a volatile reddish-brown liquid that gives off suffocating vapors, is corrosive to the skin, and may cause severe gastroenteritis if ingested. [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] Caesarean section: A surgical incision through the abdominal and uterine walls in order to deliver a baby. [NIH] Caffeine: A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes smooth muscle, stimulates cardiac muscle, stimulates diuresis, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. [NIH] Calcification: Deposits of calcium in the tissues of the breast. Calcification in the breast can be seen on a mammogram, but cannot be detected by touch. There are two types of breast calcification, macrocalcification and microcalcification. Macrocalcifications are large deposits and are usually not related to cancer. Microcalcifications are specks of calcium that may be found in an area of rapidly dividing cells. Many microcalcifications clustered together may be a sign of cancer. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calcium channel blocker: A drug used to relax the blood vessel and heart muscle, causing pressure inside blood vessels to drop. It also can regulate heart rhythm. [NIH] Callus: A callosity or hard, thick skin; the bone-like reparative substance that is formed round the edges and fragments of broken bone. [NIH] Camphor: A bicyclic monoterpene ketone found widely in plant (primarily the camphor tree, Cinnamomum camphora). Natural camphor is used topically as a skin antipruritic and as an anti-infective agent. [NIH] Candidiasis: Infection with a fungus of the genus Candida. It is usually a superficial infection of the moist cutaneous areas of the body, and is generally caused by C. albicans; it most commonly involves the skin (dermatocandidiasis), oral mucous membranes (thrush, def. 1), respiratory tract (bronchocandidiasis), and vagina (vaginitis). Rarely there is a systemic infection or endocarditis. Called also moniliasis, candidosis, oidiomycosis, and formerly blastodendriosis. [EU] Capecitabine: An anticancer drug that belongs to the family of drugs called antimetabolites.
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[NIH]
Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Captopril: A potent and specific inhibitor of peptidyl-dipeptidase A. It blocks the conversion of angiotensin I to angiotensin II, a vasoconstrictor and important regulator of arterial blood pressure. Captopril acts to suppress the renin-angiotensin system and inhibits pressure responses to exogenous angiotensin. [NIH] 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] Carboplatin: An organoplatinum compound that possesses antineoplastic activity. [NIH] Carcinogen: Any substance that causes cancer. [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] Cardiomyopathy: A general diagnostic term designating primary myocardial disease, often of obscure or unknown etiology. [EU] Cardioselective: Having greater activity on heart tissue than on other tissue. [EU] Cardiotonic: 1. Having a tonic effect on the heart. 2. An agent that has a tonic effect on the heart. [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] Catechol: A chemical originally isolated from a type of mimosa tree. Catechol is used as an astringent, an antiseptic, and in photography, electroplating, and making other chemicals. It can also be man-made. [NIH] Catheterization: Use or insertion of a tubular device into a duct, blood vessel, hollow organ,
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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] Catheters: A small, flexible tube that may be inserted into various parts of the body to inject or remove liquids. [NIH] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] Celecoxib: A drug that reduces pain. Celecoxib belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is being studied for cancer prevention. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Cycle: The complex series of phenomena, occurring between the end of one cell division and the end of the next, by which cellular material is divided between daughter cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell 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] Cellulose: A polysaccharide with glucose units linked as in cellobiose. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Central Nervous System Infections: Pathogenic infections of the brain, spinal cord, and meninges. DNA virus infections; RNA virus infections; bacterial infections; mycoplasma infections; Spirochaetales infections; fungal infections; protozoan infections; helminthiasis; and prion diseases may involve the central nervous system as a primary or secondary process. [NIH] Centrifugation: A method of separating organelles or large molecules that relies upon differential sedimentation through a preformed density gradient under the influence of a gravitational field generated in a centrifuge. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Angiography: Radiography of the vascular system of the brain after injection of a contrast medium. [NIH] 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] Check-up: A general physical examination. [NIH] Chelation: Combination with a metal in complexes in which the metal is part of a ring. [EU] Chelation Therapy: Therapy of heavy metal poisoning using agents which sequester the metal from organs or tissues and bind it firmly within the ring structure of a new compound
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which can be eliminated from the body. [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] Chemotherapy: Treatment with anticancer drugs. [NIH] Chiropractic: A system of treating bodily disorders by manipulation of the spine and other parts, based on the belief that the cause is the abnormal functioning of a nerve. [NIH] Chlorine: A greenish-yellow, diatomic gas that is a member of the halogen family of elements. It has the atomic symbol Cl, atomic number 17, and atomic weight 70.906. It is a powerful irritant that can cause fatal pulmonary edema. Chlorine is used in manufacturing, as a reagent in synthetic chemistry, for water purification, and in the production of chlorinated lime, which is used in fabric bleaching. [NIH] Chloroform: A commonly used laboratory solvent. It was previously used as an anesthetic, but was banned from use in the U.S. due to its suspected carcinogenecity. [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] Cholestyramine: Strongly basic anion exchange resin whose main constituent is polystyrene trimethylbenzylammonium as Cl(-) anion. It exchanges chloride ions with bile salts, thus decreasing their concentration and that of cholesterol. It is used as a hypocholesteremic in diarrhea and biliary obstruction and as an antipruritic. [NIH] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] 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] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Chronic Fatigue Syndrome: Fatigue caused by the combined effects of different types of prolonged fatigue. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Chylomicrons: A class of lipoproteins that carry dietary cholesterol and triglycerides from the small intestines to the tissues. [NIH] Cinchona: A genus of rubiaceous South American trees that yields the toxic cinchona alkaloids from their bark; quinine, quinidine, chinconine, cinchonidine and others are used to treat malaria and cardiac arrhythmias. [NIH]
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Ciprofloxacin: A carboxyfluoroquinoline antimicrobial agent that is effective against a wide range of microorganisms. It has been successfully and safely used in the treatment of resistant respiratory, skin, bone, joint, gastrointestinal, urinary, and genital infections. [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] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]
Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Clot Retraction: Retraction of a clot resulting from contraction of platelet pseudopods attached to fibrin strands that is dependent on the contractile protein thrombosthenin. Used as a measure of platelet function. [NIH] 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] Coal: A natural fuel formed by partial decomposition of vegetable matter under certain environmental conditions. [NIH] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cognition: Intellectual or mental process whereby an organism becomes aware of or obtains knowledge. [NIH] Colitis: Inflammation of the colon. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Colloidal: Of the nature of a colloid. [EU] Colorectal: Having to do with the colon or the rectum. [NIH] Combination chemotherapy: Treatment using more than one anticancer drug. [NIH]
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Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computer Simulation: Computer-based representation of physical systems and phenomena such as chemical processes. [NIH] Computerized axial tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography (CT scan), or computerized tomography. [NIH]
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Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Concomitant: Accompanying; accessory; joined with another. [EU] Confounding: Extraneous variables resulting in outcome effects that obscure or exaggerate the "true" effect of an intervention. [NIH] Confusion: A mental state characterized by bewilderment, emotional disturbance, lack of clear thinking, and perceptual disorientation. [NIH] Congenita: Displacement, subluxation, or malposition of the crystalline lens. [NIH] Congestive heart failure: Weakness of the heart muscle that leads to a buildup of fluid in body tissues. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjugation: 1. The act of joining together or the state of being conjugated. 2. A sexual process seen in bacteria, ciliate protozoa, and certain fungi in which nuclear material is exchanged during the temporary fusion of two cells (conjugants). In bacterial genetics a form of sexual reproduction in which a donor bacterium (male) contributes some, or all, of its DNA (in the form of a replicated set) to a recipient (female) which then incorporates differing genetic information into its own chromosome by recombination and passes the recombined set on to its progeny by replication. In ciliate protozoa, two conjugants of separate mating types exchange micronuclear material and then separate, each now being a fertilized cell. In certain fungi, the process involves fusion of two gametes, resulting in union of their nuclei and formation of a zygote. 3. In chemistry, the joining together of two compounds to produce another compound, such as the combination of a toxic product with some substance in the body to form a detoxified product, which is then eliminated. [EU] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue Diseases: A heterogeneous group of disorders, some hereditary, others acquired, characterized by abnormal structure or function of one or more of the elements of connective tissue, i.e., collagen, elastin, or the mucopolysaccharides. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constriction: The act of constricting. [NIH] Consultation: A deliberation between two or more physicians concerning the diagnosis and the proper method of treatment in a case. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Contraception: Use of agents, devices, methods, or procedures which diminish the likelihood of or prevent conception. [NIH] Contractility: Capacity for becoming short in response to a suitable stimulus. [EU] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Contrast Media: Substances used in radiography that allow visualization of certain tissues. [NIH]
Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH]
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Controlled study: An experiment or clinical trial that includes a comparison (control) group. [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] Corn Oil: Oil from corn or corn plant. [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 Disease: Disorder of cardiac function due to an imbalance between myocardial function and the capacity of the coronary vessels to supply sufficient flow for normal function. It is a form of myocardial ischemia (insufficient blood supply to the heart muscle) caused by a decreased capacity of the coronary vessels. [NIH] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Coronary Vessels: The veins and arteries of the heart. [NIH] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Corticosteroid: Any of the steroids elaborated by the adrenal cortex (excluding the sex hormones of adrenal origin) in response to the release of corticotrophin (adrenocorticotropic hormone) by the pituitary gland, to any of the synthetic equivalents of these steroids, or to angiotensin II. They are divided, according to their predominant biological activity, into three major groups: glucocorticoids, chiefly influencing carbohydrate, fat, and protein metabolism; mineralocorticoids, affecting the regulation of electrolyte and water balance; and C19 androgens. Some corticosteroids exhibit both types of activity in varying degrees, and others exert only one type of effect. The corticosteroids are used clinically for hormonal replacement therapy, for suppression of ACTH secretion by the anterior pituitary, as antineoplastic, antiallergic, and anti-inflammatory agents, and to suppress the immune response. Called also adrenocortical hormone and corticoid. [EU] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cortisone: A natural steroid hormone produced in the adrenal gland. It can also be made in the laboratory. Cortisone reduces swelling and can suppress immune responses. [NIH] Coumarin: A fluorescent dye. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] Creatinine: A compound that is excreted from the body in urine. Creatinine levels are
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measured to monitor kidney function. [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 compounds that contain a ring of atoms in the nucleus. [EU] Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Data Collection: Systematic gathering of data for a particular purpose from various sources, including questionnaires, interviews, observation, existing records, and electronic devices. The process is usually preliminary to statistical analysis of the data. [NIH] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH] 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] Delivery of Health Care: The concept concerned with all aspects of providing and distributing health services to a patient population. [NIH] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Depressive Disorder: An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent. [NIH] Detoxification: Treatment designed to free an addict from his drug habit. [EU] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH]
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Diabetes Insipidus: A metabolic disorder due to disorders in the production or release of vasopressin. It is characterized by the chronic excretion of large amounts of low specific gravity urine and great thirst. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diabetic Retinopathy: Retinopathy associated with diabetes mellitus, which may be of the background type, progressively characterized by microaneurysms, interretinal punctuate macular edema, or of the proliferative type, characterized by neovascularization of the retina and optic disk, which may project into the vitreous, proliferation of fibrous tissue, vitreous hemorrhage, and retinal detachment. [NIH] Diagnostic Errors: Incorrect diagnoses after clinical examination or technical diagnostic procedures. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Dialyzer: A part of the hemodialysis machine. (See hemodialysis under dialysis.) The dialyzer has two sections separated by a membrane. One section holds dialysate. The other holds the patient's blood. [NIH] 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] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Digitalis: A genus of toxic herbaceous Eurasian plants of the Scrophulaceae which yield cardiotonic glycosides. The most useful are Digitalis lanata and D. purpurea. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Dihydroxy: AMPA/Kainate antagonist. [NIH] Dilatation: The act of dilating. [NIH] Diploid: Having two sets of chromosomes. [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] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] 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
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roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Dissociative Disorders: Sudden temporary alterations in the normally integrative functions of consciousness. [NIH] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Diuresis: Increased excretion of urine. [EU] Diuretic: A drug that increases the production of urine. [NIH] Dosage Forms: Completed forms of the pharmaceutical preparation in which prescribed doses of medication are included. They are designed to resist action by gastric fluids, prevent vomiting and nausea, reduce or alleviate the undesirable taste and smells associated with oral administration, achieve a high concentration of drug at target site, or produce a delayed or long-acting drug effect. They include capsules, liniments, ointments, pharmaceutical solutions, powders, tablets, etc. [NIH] Doxycycline: A synthetic tetracycline derivative with a range of antimicrobial activity and mode of action similar to that of tetracycline, but more effective against many species. Animal studies suggest that it may cause less tooth staining than other tetracyclines. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Duodenum: The first part of the small intestine. [NIH] Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dyslipidemia: Disorders in the lipoprotein metabolism; classified as hypercholesterolemia, hypertriglyceridemia, combined hyperlipidemia, and low levels of high-density lipoprotein (HDL) cholesterol. All of the dyslipidemias can be primary or secondary. Both elevated levels of low-density lipoprotein (LDL) cholesterol and low levels of HDL cholesterol predispose to premature atherosclerosis. [NIH] Dyspareunia: Painful sexual intercourse. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] 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] Ejection fraction: A measure of ventricular contractility, equal to normally 65 8 per cent; lower values indicate ventricular dysfunction. [EU] Elastin: The protein that gives flexibility to tissues. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electrocoagulation: Electrosurgical procedures used to treat hemorrhage (e.g., bleeding ulcers) and to ablate tumors, mucosal lesions, and refractory arrhythmias. [NIH]
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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] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH]
Electroplating: Coating with a metal or alloy by electrolysis. [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] Embryogenesis: The process of embryo or embryoid formation, whether by sexual (zygotic) or asexual means. In asexual embryogenesis embryoids arise directly from the explant or on intermediary callus tissue. In some cases they arise from individual cells (somatic cell embryoge). [NIH] Empiric: Empirical; depending upon experience or observation alone, without using scientific method or theory. [EU] Empirical: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] Enalapril: An angiotensin-converting enzyme inhibitor that is used to treat hypertension. [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] Endometriosis: A condition in which tissue more or less perfectly resembling the uterine mucous membrane (the endometrium) and containing typical endometrial granular and stromal elements occurs aberrantly in various locations in the pelvic cavity. [NIH] Endophthalmitis: Suppurative inflammation of the tissues of the internal structures of the eye; not all layers of the uvea are affected. Fungi, necrosis of intraocular tumors, and retained intraocular foreign bodies often cause a purulent endophthalmitis. [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]
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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] Endotoxic: Of, relating to, or acting as an endotoxin (= a heat-stable toxin, associated with the outer membranes of certain gram-negative bacteria. Endotoxins are not secreted and are released only when the cells are disrupted). [EU] Endotoxin: Toxin from cell walls of bacteria. [NIH] Enoxaparin: A drug used to prevent blood clots. It belongs to the family of drugs called anticoagulants. [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] Epidemiological: Relating to, or involving epidemiology. [EU] Epidural: The space between the wall of the spinal canal and the covering of the spinal cord. An epidural injection is given into this space. [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [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] 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]
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Ether: One of a class of organic compounds in which any two organic radicals are attached directly to a single oxygen atom. [NIH] Ethnic Groups: A group of people with a common cultural heritage that sets them apart from others in a variety of social relationships. [NIH] Etoposide: A semisynthetic derivative of podophyllotoxin that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Excipients: Usually inert substances added to a prescription in order to provide suitable consistency to the dosage form; a binder, matrix, base or diluent in pills, tablets, creams, salves, etc. [NIH] Excitability: Property of a cardiac cell whereby, when the cell is depolarized to a critical level (called threshold), the membrane becomes permeable and a regenerative inward current causes an action potential. [NIH] Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] Exhaustion: The feeling of weariness of mind and body. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exon: The part of the DNA that encodes the information for the actual amino acid sequence of the protein. In many eucaryotic genes, the coding sequences consist of a series of exons alternating with intron sequences. [NIH] 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] 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] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [EU] F Factor: A plasmid whose presence in the cell, either extrachromosomal or integrated into the bacterial chromosome, determines the "sex" of the bacterium, host chromosome mobilization, transfer via conjugation of genetic material, and the formation of sex pili. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]
Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU]
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Fetal Development: Morphologic and physiologic growth and development of the mammalian embryo or fetus. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] 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] Fibrinolytic: Pertaining to, characterized by, or causing the dissolution of fibrin by enzymatic action [EU] Fistulas: An abnormal passage from one hollow structure of the body to another, or from a hollow structure to the surface, formed by an abscess, disease process, incomplete closure of a wound, or by a congenital anomaly. [NIH] Flatus: Gas passed through the rectum. [NIH] Fluconazole: Triazole antifungal agent that is used to treat oropharyngeal candidiasis and cryptococcal meningitis in AIDS. [NIH] Fluorouracil: A pyrimidine analog that acts as an antineoplastic antimetabolite and also has 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] Focus Groups: A method of data collection and a qualitative research tool in which a small group of individuals are brought together and allowed to interact in a discussion of their opinions about topics, issues, or questions. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Food Technology: The application of knowledge to the food industry. [NIH] Foramen: A natural hole of perforation, especially one in a bone. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] Furosemide: A sulfamyl saluretic and diuretic. It has a fast onset and short duration of action and is used in edema and chronic renal insufficiency. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gamma Rays: Very powerful and penetrating, high-energy electromagnetic radiation of shorter wavelength than that of x-rays. They are emitted by a decaying nucleus, usually between 0.01 and 10 MeV. They are also called nuclear x-rays. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Gangrene: Death and putrefaction of tissue usually due to a loss of blood supply. [NIH]
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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] Gasoline: Volative flammable fuel (liquid hydrocarbons) derived from crude petroleum by processes such as distillation reforming, polymerization, etc. [NIH] Gastric: Having to do with the stomach. [NIH] Gastric Acid: Hydrochloric acid present in gastric juice. [NIH] Gastric Mucosa: Surface epithelium in the stomach that invaginates into the lamina propria, forming gastric pits. Tubular glands, characteristic of each region of the stomach (cardiac, gastric, and pyloric), empty into the gastric pits. The gastric mucosa is made up of several different kinds of cells. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]
Gastritis: Inflammation of the stomach. [EU] Gastroenteritis: An acute inflammation of the lining of the stomach and intestines, characterized by anorexia, nausea, diarrhoea, abdominal pain, and weakness, which has various causes, including food poisoning due to infection with such organisms as Escherichia coli, Staphylococcus aureus, and Salmonella species; consumption of irritating food or drink; or psychological factors such as anger, stress, and fear. Called also enterogastritis. [EU] Gastroenterology: A subspecialty of internal medicine concerned with the study of the physiology and diseases of the digestive system and related structures (esophagus, liver, gallbladder, and pancreas). [NIH] Gastroesophageal Reflux: Reflux of gastric juice and/or duodenal contents (bile acids, pancreatic juice) into the distal esophagus, commonly due to incompetence of the lower esophageal sphincter. Gastric regurgitation is an extension of this process with entry of fluid into the pharynx or mouth. [NIH] 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]
Genetic Techniques: Chromosomal, biochemical, intracellular, and other methods used in the study of genetics. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genital: Pertaining to the genitalia. [EU] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Giardiasis: An infection of the small intestine caused by the flagellated protozoan Giardia lamblia. It is spread via contaminated food and water and by direct person-to-person contact. [NIH] Ginger: Deciduous plant rich in volatile oil (oils, volatile). It is used as a flavoring agent and has many other uses both internally and topically. [NIH] Ginseng: An araliaceous genus of plants that contains a number of pharmacologically active agents used as stimulants, sedatives, and tonics, especially in traditional medicine. [NIH]
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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]
Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [NIH] 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] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]
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] Glycols: A generic grouping for dihydric alcohols with the hydroxy groups (-OH) located on different carbon atoms. They are viscous liquids with high boiling points for their molecular weights. [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] Glycoside: Any compound that contains a carbohydrate molecule (sugar), particularly any such natural product in plants, convertible, by hydrolytic cleavage, into sugar and a nonsugar component (aglycone), and named specifically for the sugar contained, as glucoside (glucose), pentoside (pentose), fructoside (fructose) etc. [EU] Gout: Hereditary metabolic disorder characterized by recurrent acute arthritis, hyperuricemia and deposition of sodium urate in and around the joints, sometimes with formation of uric acid calculi. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH]
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Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Grafting: The operation of transfer of tissue from one site to another. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Haematoma: A localized collection of blood, usually clotted, in an organ, space, or tissue, due to a break in the wall of a blood vessel. [EU] Haemodialysis: The removal of certain elements from the blood by virtue of the difference in the rates of their diffusion through a semipermeable membrane, e.g., by means of a haemodialyzer. [EU] Haemorrhage: The escape of blood from the vessels; bleeding. Small haemorrhages are classified according to size as petechiae (very small), purpura (up to 1 cm), and ecchymoses (larger). The massive accumulation of blood within a tissue is called a haematoma. [EU] Haploid: An organism with one basic chromosome set, symbolized by n; the normal condition of gametes in diploids. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Headache Disorders: Common conditions characterized by persistent or recurrent headaches. Headache syndrome classification systems may be based on etiology (e.g., vascular headache, post-traumatic headaches, etc.), temporal pattern (e.g., cluster headache, paroxysmal hemicrania, etc.), and precipitating factors (e.g., cough headache). [NIH] Health Care Costs: The actual costs of providing services related to the delivery of health care, including the costs of procedures, therapies, and medications. It is differentiated from health expenditures, which refers to the amount of money paid for the services, and from fees, which refers to the amount charged, regardless of cost. [NIH] Health Expenditures: The amounts spent by individuals, groups, nations, or private or public organizations for total health care and/or its various components. These amounts may or may not be equivalent to the actual costs (health care costs) and may or may not be shared among the patient, insurers, and/or employers. [NIH] Health 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 Transplantation: The transference of a heart from one human or animal to another. [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]
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Heartburn: Substernal pain or burning sensation, usually associated with regurgitation of gastric juice into the esophagus. [NIH] Hematology: A subspecialty of internal medicine concerned with morphology, physiology, and pathology of the blood and blood-forming tissues. [NIH] Hematoma: An extravasation of blood localized in an organ, space, or tissue. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemorrhaging: A copious discharge of blood from the blood vessels. [NIH] Hemorrhoid: An enlarged or swollen blood vessel, usually located near the anus or the rectum. [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] Hepatocellular: Pertaining to or affecting liver cells. [EU] Hepatocellular carcinoma: A type of adenocarcinoma, the most common type of liver tumor. [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] 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]
Heterotropic: Of organisms that cannot live without an external source of organic food. [NIH]
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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] Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Hydralazine: A direct-acting vasodilator that is used as an antihypertensive agent. [NIH] Hydrochlorothiazide: A thiazide diuretic often considered the prototypical member of this class. It reduces the reabsorption of electrolytes from the renal tubules. This results in increased excretion of water and electrolytes, including sodium, potassium, chloride, and magnesium. It has been used in the treatment of several disorders including edema, hypertension, diabetes insipidus, and hypoparathyroidism. [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] Hydrolases: Any member of the class of enzymes that catalyze the cleavage of the substrate and the addition of water to the resulting molecules, e.g., esterases, glycosidases (glycoside hydrolases), lipases, nucleotidases, peptidases (peptide hydrolases), and phosphatases (phosphoric monoester hydrolases). EC 3. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophilic: Readily absorbing moisture; hygroscopic; having strongly polar groups that readily interact with water. [EU] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hydroxylation: Hydroxylate, to introduce hydroxyl into (a compound or radical) usually by replacement of hydrogen. [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] Hypercholesterolemia: Abnormally high levels of cholesterol in the blood. [NIH] Hyperlipidemia: An excess of lipids in the blood. [NIH]
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Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hypertriglyceridemia: Condition of elevated triglyceride concentration in the blood; an inherited form occurs in familial hyperlipoproteinemia IIb and hyperlipoproteinemia type IV. It has been linked to higher risk of heart disease and arteriosclerosis. [NIH] Hypnotic: A drug that acts to induce sleep. [EU] Hypoplasia: Incomplete development or underdevelopment of an organ or tissue. [EU] Hypothyroidism: Deficiency of thyroid activity. In adults, it is most common in women and is characterized by decrease in basal metabolic rate, tiredness and lethargy, sensitivity to cold, and menstrual disturbances. If untreated, it progresses to full-blown myxoedema. In infants, severe hypothyroidism leads to cretinism. In juveniles, the manifestations are intermediate, with less severe mental and developmental retardation and only mild symptoms of the adult form. When due to pituitary deficiency of thyrotropin secretion it is called secondary hypothyroidism. [EU] Iatrogenic: Resulting from the activity of physicians. Originally applied to disorders induced in the patient by autosuggestion based on the physician's examination, manner, or discussion, the term is now applied to any adverse condition in a patient occurring as the result of treatment by a physician or surgeon, especially to infections acquired by the patient during the course of treatment. [EU] Ibuprofen: A nonsteroidal anti-inflammatory agent with analgesic properties used in the therapy of rheumatism and arthritis. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Imidazole: C3H4N2. The ring is present in polybenzimidazoles. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]
Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunodiffusion: Technique involving the diffusion of antigen or antibody through a semisolid medium, usually agar or agarose gel, with the result being a precipitin reaction. [NIH]
Immunoelectrophoresis: A technique that combines protein electrophoresis and double immunodiffusion. In this procedure proteins are first separated by gel electrophoresis (usually agarose), then made visible by immunodiffusion of specific antibodies. A distinct elliptical precipitin arc results for each protein detectable by the antisera. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH]
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Immunology: The study of the body's immune system. [NIH] Immunosuppressant: An agent capable of suppressing immune responses. [EU] 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] 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] Incompetence: Physical or mental inadequacy or insufficiency. [EU] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Indomethacin: A non-steroidal anti-inflammatory agent (NSAID) that inhibits the enzyme cyclooxygenase necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes. [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]
Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Inflammatory bowel disease: A general term that refers to the inflammation of the colon and rectum. Inflammatory bowel disease includes ulcerative colitis and Crohn's disease. [NIH]
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] 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
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psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Interindividual: Occurring between two or more individuals. [EU] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] 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] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intraocular: Within the eye. [EU] Intravascular: Within a vessel or vessels. [EU] Intravenous: IV. Into a vein. [NIH] Intravesical: Within the bladder. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]
Involuntary: Reaction occurring without intention or volition. [NIH] Ionization: 1. Any process by which a neutral atom gains or loses electrons, thus acquiring a net charge, as the dissociation of a substance in solution into ions or ion production by the passage of radioactive particles. 2. Iontophoresis. [EU] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] 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
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bringing blood to the brain. When it becomes blocked, the risk of stroke is very high. [NIH] Isoelectric: Separation of amphoteric substances, dissolved in water, based on their isoelectric behavior. The amphoteric substances are a mixture of proteins to be separated and of auxiliary "carrier ampholytes". [NIH] Isoelectric Focusing: Electrophoresis in which a pH gradient is established in a gel medium and proteins migrate until they reach the site (or focus) at which the pH is equal to their isoelectric point. [NIH] Isoelectric Point: The pH in solutions of proteins and related compounds at which the dipolar ions are at a maximum. [NIH] Isopropyl: A gene mutation inducer. [NIH] Isozymes: The multiple forms of a single enzyme. [NIH] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Keto: It consists of 8 carbon atoms and within the endotoxins, it connects poysaccharide and lipid A. [NIH] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Kinetic: Pertaining to or producing motion. [EU] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Leg Ulcer: Ulceration of the skin and underlying structures of the lower extremity. About 90% of the cases are due to venous insufficiency (varicose ulcer), 5% to arterial disease, and the remaining 5% to other causes. [NIH] Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] Lethargy: Abnormal drowsiness or stupor; a condition of indifference. [EU] Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Leukotrienes: A family of biologically active compounds derived from arachidonic acid by oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal
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tract and the immune system. [NIH] Levofloxacin: A substance used to treat bacterial infections. It belongs to the family of drugs called quinolone antibiotics. [NIH] Levonorgestrel: A progestational hormone with actions similar to those of progesterone and about twice as potent as its racemic or (+-)-isomer (norgestrel). It is used for contraception, control of menstrual disorders, and treatment of endometriosis. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]
Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Ligands: A RNA simulation method developed by the MIT. [NIH] Ligase: An enzyme that repairs single stranded discontinuities in double-stranded DNA molecules in the cell. Purified DNA ligase is used in gene cloning to join DNA molecules together. [NIH] Lipid: Fat. [NIH] Lipid A: Lipid A is the biologically active component of lipopolysaccharides. It shows strong endotoxic activity and exhibits immunogenic properties. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipopolysaccharides: Substance consisting of polysaccaride and lipid. [NIH] 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] Lipoxygenase: An enzyme of the oxidoreductase class that catalyzes reactions between linoleate and other fatty acids and oxygen to form hydroperoxy-fatty acid derivatives. Related enzymes in this class include the arachidonate lipoxygenases, arachidonate 5lipoxygenase, arachidonate 12-lipoxygenase, and arachidonate 15-lipoxygenase. EC 1.13.11.12. [NIH] Lisinopril: An orally active angiotensin-converting enzyme inhibitor that has been used in the treatment of hypertension and congestive heart failure. [NIH] Lithium: An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight 6.94. Salts of lithium are used in treating manic-depressive disorders. [NIH]
Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver cancer: A disease in which malignant (cancer) cells are found in the tissues of the liver. [NIH]
Liver scan: An image of the liver created on a computer screen or on film. A radioactive substance is injected into a blood vessel and travels through the bloodstream. It collects in the liver, especially in abnormal areas, and can be detected by the scanner. [NIH] Loading dose: A quantity higher than the average or maintenance dose, used at the initiation of therapy to rapidly establish a desired level of the drug [EU] Localized: Cancer which has not metastasized yet. [NIH] Locomotion: Movement or the ability to move from one place or another. It can refer to
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humans, vertebrate or invertebrate animals, and microorganisms. [NIH] Long-Term Care: Care over an extended period, usually for a chronic condition or disability, requiring periodic, intermittent, or continuous care. [NIH] Loop: A wire usually of platinum bent at one end into a small loop (usually 4 mm inside diameter) and used in transferring microorganisms. [NIH] 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] Lower Esophageal Sphincter: The muscle between the esophagus and stomach. When a person swallows, this muscle relaxes to let food pass from the esophagus to the stomach. It stays closed at other times to keep stomach contents from flowing back into the esophagus. [NIH]
Lumen: The cavity or channel within a tube or tubular organ. [EU] 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] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Macula: A stain, spot, or thickening. Often used alone to refer to the macula retinae. [EU] Macula Lutea: An oval area in the retina, 3 to 5 mm in diameter, usually located temporal to the superior pole of the eye and slightly below the level of the optic disk. [NIH] Macular Degeneration: Degenerative changes in the macula lutea of the retina. [NIH] Magnetic Resonance Angiography: Non-invasive method of vascular imaging and determination of internal anatomy without injection of contrast media or radiation exposure. The technique is used especially in cerebral angiography as well as for studies of other vascular structures. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Malignancy: A cancerous tumor that can invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]
Mammary: Pertaining to the mamma, or breast. [EU] Mammogram: An x-ray of the breast. [NIH]
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Mandible: The largest and strongest bone of the face constituting the lower jaw. It supports the lower teeth. [NIH] Manic: Affected with mania. [EU] Man-made: Ionizing radiation emitted by artificial or concentrated natural, radioactive material or resulting from the operation of high voltage apparatus, such as X-ray apparatus or particle accelerators, of nuclear reactors, or from nuclear explosions. [NIH] Maternal Exposure: Exposure of the female parent, human or animal, to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals that may affect offspring. It includes pre-conception maternal exposure. [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 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] Melanin: The substance that gives the skin its color. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meningeal: Refers to the meninges, the tissue covering the brain and spinal cord. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Meningitis: Inflammation of the meninges. When it affects the dura mater, the disease is termed pachymeningitis; when the arachnoid and pia mater are involved, it is called leptomeningitis, or meningitis proper. [EU] Mental 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] Mentors: Senior professionals who provide guidance, direction and support to those persons desirous of improvement in academic positions, administrative positions or other career development situations. [NIH] Mercaptopurine: An anticancer drug that belongs to the family of drugs called antimetabolites. [NIH] Meta-Analysis: A quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions
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which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with application chiefly in the areas of research and medicine. [NIH] Metabolic disorder: A condition in which normal metabolic processes are disrupted, usually because of a missing enzyme. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] Methyl salicylate: Non-steroidal anti-inflammatory drugs. [NIH] Methylene Chloride: A chlorinated hydrocarbon that has been used as an inhalation anesthetic and acts as a narcotic in high concentrations. Its primary use is as a solvent in manufacturing and food technology. [NIH] Methyltransferase: A drug-metabolizing enzyme. [NIH] Metoprolol: Adrenergic beta-1-blocking agent with no stimulatory action. It is less bound to plasma albumin than alprenolol and may be useful in angina pectoris, hypertension, or cardiac arrhythmias. [NIH] Metronidazole: Antiprotozoal used in amebiasis, trichomoniasis, giardiasis, and as treponemacide in livestock. It has also been proposed as a radiation sensitizer for hypoxic cells. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985, p133), this substance may reasonably be anticipated to be a carcinogen (Merck, 11th ed). [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Micelle: A colloid particle formed by an aggregation of small molecules. [EU] Miconazole: An imidazole antifungal agent that is used topically and by intravenous infusion. [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] Microcalcifications: Tiny deposits of calcium in the breast that cannot be felt but can be detected on a mammogram. A cluster of these very small specks of calcium may indicate that cancer is present. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Microsomal: Of or pertaining to microsomes : vesicular fragments of endoplasmic reticulum formed after disruption and centrifugation of cells. [EU] Mineralization: The action of mineralizing; the state of being mineralized. [EU] Mineralocorticoids: A group of corticosteroids primarily associated with the regulation of water and electrolyte balance. This is accomplished through the effect on ion transport in
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renal tubules, resulting in retention of sodium and loss of potassium. Mineralocorticoid secretion is itself regulated by plasma volume, serum potassium, and angiotensin II. [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] Mitotic: Cell resulting from mitosis. [NIH] Mobility: Capability of movement, of being moved, or of flowing freely. [EU] Mobilization: The process of making a fixed part or stored substance mobile, as by separating a part from surrounding structures to make it accessible for an operative procedure or by causing release into the circulation for body use of a substance stored in the body. [EU] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monoclonal antibodies: Laboratory-produced substances that can locate and bind to cancer cells wherever they are in the body. Many monoclonal antibodies are used in cancer detection or therapy; each one recognizes a different protein on certain cancer cells. Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to a tumor. [NIH] 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] Morphological: Relating to the configuration or the structure of live organs. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motility: The ability to move spontaneously. [EU] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness, and air sickness. [NIH] Mucosa: A mucous membrane, or tunica mucosa. [EU] Muscular Dystrophies: A general term for a group of inherited disorders which are characterized by progressive degeneration of skeletal muscles. [NIH] Musculoskeletal System: Themuscles, bones, and cartilage of the body. [NIH] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be
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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] Myelosuppression: A condition in which bone marrow activity is decreased, resulting in fewer red blood cells, white blood cells, and platelets. Myelosuppression is a side effect of some cancer treatments. [NIH] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocardial Ischemia: A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (coronary arteriosclerosis), to obstruction by a thrombus (coronary thrombosis), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result in necrosis of cardiac muscle (myocardial infarction). [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myotonia: Prolonged failure of muscle relaxation after contraction. This may occur after voluntary contractions, muscle percussion, or electrical stimulation of the muscle. Myotonia is a characteristic feature of myotonic disorders. [NIH] Myotonic Dystrophy: A condition presenting muscle weakness and wasting which may be progressive. [NIH] Narcotic: 1. Pertaining to or producing narcosis. 2. An agent that produces insensibility or stupor, applied especially to the opioids, i.e. to any natural or synthetic drug that has morphine-like actions. [EU] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Nephrology: A subspecialty of internal medicine concerned with the anatomy, physiology, and pathology of the kidney. [NIH] Nephropathy: Disease of the kidneys. [EU] Nephrotoxic: Toxic or destructive to kidney cells. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and
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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] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropeptides: Peptides released by neurons as intercellular messengers. Many neuropeptides are also hormones released by non-neuronal cells. [NIH] Neurotoxicity: The tendency of some treatments to cause damage to the nervous system. [NIH]
Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Nevirapine: A potent, non-nucleoside reverse transcriptase inhibitor used in combination with nucleoside analogues for treatment of HIV infection and AIDS. [NIH] Nicotine: Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke. [NIH] Nitrates: Inorganic or organic salts and esters of nitric acid. These compounds contain the NO3- radical. [NIH] Nitric acid: A toxic, corrosive, colorless liquid used to make fertilizers, dyes, explosives, and other chemicals. [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] Non-nucleoside: A member of a class of compounds, including delavirdine, loviride and nevirapine, that acts to directly combine with and block the action of HIV's reverse transcriptase. [NIH] Norgestrel: (+-)-13-Ethyl-17-hydroxy-18,19-dinorpregn-4-en-20-yn-3-one. A progestational agent with actions similar to those of progesterone. This racemic or (+-)-form has about half the potency of the levo form (levonorgestrel). Norgestrel is used as a contraceptive and ovulation inhibitor and for the control of menstrual disorders and endometriosis. [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] 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] Nucleotidases: A class of enzymes that catalyze the conversion of a nucleotide and water to
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a nucleoside and orthophosphate. EC 3.1.3.-. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nursing Staff: Personnel who provide nursing service to patients in an organized facility, institution, or agency. [NIH] Observational study: An epidemiologic study that does not involve any intervention, experimental or otherwise. Such a study may be one in which nature is allowed to take its course, with changes in one characteristic being studied in relation to changes in other characteristics. Analytical epidemiologic methods, such as case-control and cohort study designs, are properly called observational epidemiology because the investigator is observing without intervention other than to record, classify, count, and statistically analyze results. [NIH] Occult: Obscure; concealed from observation, difficult to understand. [EU] Occupational Medicine: Medical specialty concerned with the promotion and maintenance of the physical and mental health of employees in occupational settings. [NIH] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Odour: A volatile emanation that is perceived by the sense of smell. [EU] Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Oncology: The study of cancer. [NIH] On-line: A sexually-reproducing population derived from a common parentage. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Optic Disk: The portion of the optic nerve seen in the fundus with the ophthalmoscope. It is formed by the meeting of all the retinal ganglion cell axons as they enter the optic nerve. [NIH]
Oral Health: The optimal state of the mouth and normal functioning of the organs of the mouth without evidence of disease. [NIH] Orthopaedic: Pertaining to the correction of deformities of the musculoskeletal system; pertaining to orthopaedics. [EU] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [NIH] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Overdosage: 1. The administration of an excessive dose. 2. The condition resulting from an excessive dose. [EU] Overdose: An accidental or deliberate dose of a medication or street drug that is in excess of what is normally used. [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
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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] 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] Pancreatitis: Acute or chronic inflammation of the pancreas, which may be asymptomatic or symptomatic, and which is due to autodigestion of a pancreatic tissue by its own enzymes. It is caused most often by alcoholism or biliary tract disease; less commonly it may be associated with hyperlipaemia, hyperparathyroidism, abdominal trauma (accidental or operative injury), vasculitis, or uraemia. [EU] Parathion: A highly toxic cholinesterase inhibitor that is used as an acaricide and as an insecticide. [NIH] Parenchyma: The essential elements of an organ; used in anatomical nomenclature as a general term to designate the functional elements of an organ, as distinguished from its framework, or stroma. [EU] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Parenteral Nutrition: The administering of nutrients for assimilation and utilization by a patient who cannot maintain adequate nutrition by enteral feeding alone. Nutrients are administered by a route other than the alimentary canal (e.g., intravenously, subcutaneously). [NIH] Particle: A tiny mass of material. [EU] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]
Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]
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Patient Satisfaction: The degree to which the individual regards the health care service or product or the manner in which it is delivered by the provider as useful, effective, or beneficial. [NIH] Pediatrics: A medical specialty concerned with maintaining health and providing medical care to children from birth to adolescence. [NIH] Pelvic: Pertaining to the pelvis. [EU] 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] Peptide Hydrolases: A subclass of enzymes from the hydrolase class that catalyze the hydrolysis of peptide bonds. Exopeptidases and endopeptidases make up the sub-subclasses for this group. EC 3.4. [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] Perineal: Pertaining to the perineum. [EU] Perineum: The area between the anus and the sex organs. [NIH] Perioperative: Around the time of surgery; usually lasts from the time of going into the hospital or doctor's office for surgery until the time the patient goes home. [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of Winslow, or epiploic foramen. [NIH] Peritoneal Dialysis: Dialysis fluid being introduced into and removed from the peritoneal cavity as either a continuous or an intermittent procedure. [NIH] Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering the inside of the abdominal wall and the visceral peritoneum covering the bowel, the mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal layer of the bowel wall. [NIH] Petechiae: Pinpoint, unraised, round red spots under the skin caused by bleeding. [NIH] Pharmaceutical Solutions: Homogeneous liquid preparations that contain one or more chemical substances dissolved, i.e., molecularly dispersed, in a suitable solvent or mixture of mutually miscible solvents. For reasons of their ingredients, method of preparation, or use, they do not fall into another group of products. [NIH] Pharmacodynamic: Is concerned with the response of living tissues to chemical stimuli, that is, the action of drugs on the living organism in the absence of disease. [NIH] Pharmacogenetics: A branch of genetics which deals with the genetic components of variability in individual responses to and metabolism (biotransformation) of drugs. [NIH]
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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] Pharmacology, Clinical: The branch of pharmacology that deals directly with the effectiveness and safety of drugs in humans. [NIH] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenprocoumon: 3-(1-Phenylpropyl)-4-hydroxycoumarin. Long acting oral anticoagulant. It may cause diarrhea. [NIH] Phenyl: Ingredient used in cold and flu remedies. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] 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] Phosphoric Monoester Hydrolases: A group of hydrolases which catalyze the hydrolysis of monophosphoric esters with the production of one mole of orthophosphate. EC 3.1.3. [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] Phosphorylated: Attached to a phosphate group. [NIH] Photocoagulation: Using a special strong beam of light (laser) to seal off bleeding blood vessels such as in the eye. The laser can also burn away blood vessels that should not have grown in the eye. This is the main treatment for diabetic retinopathy. [NIH] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]
Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pigmentation: Coloration or discoloration of a part by a pigment. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [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]
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Plants, Toxic: Plants or plant parts which are harmful to man or other animals. [NIH] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU] Plasmid: An autonomously replicating, extra-chromosomal DNA molecule found in many bacteria. Plasmids are widely used as carriers of cloned genes. [NIH] Plasmin: A product of the lysis of plasminogen (profibrinolysin) by plasminogen activators. It is composed of two polypeptide chains, light (B) and heavy (A), with a molecular weight of 75,000. It is the major proteolytic enzyme involved in blood clot retraction or the lysis of fibrin and quickly inactivated by antiplasmins. EC 3.4.21.7. [NIH] Plasminogen: Precursor of fibrinolysin (plasmin). It is a single-chain beta-globulin of molecular weight 80-90,000 found mostly in association with fibrinogen in plasma; plasminogen activators change it to fibrinolysin. It is used in wound debriding and has been investigated as a thrombolytic agent. [NIH] Plasminogen Activators: A heterogeneous group of proteolytic enzymes that convert plasminogen to plasmin. They are concentrated in the lysosomes of most cells and in the vascular endothelium, particularly in the vessels of the microcirculation. EC 3.4.21.-. [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]
Podophyllotoxin: The main active constituent of the resin from the roots of may apple or mandrake (Podophyllum peltatum and P. emodi). It is a potent spindle poison, toxic if taken internally, and has been used as a cathartic. It is very irritating to skin and mucous membranes, has keratolytic actions, has been used to treat warts and keratoses, and may have antineoplastic properties, as do some of its congeners and derivatives. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Pollen: The male fertilizing element of flowering plants analogous to sperm in animals. It is
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released from the anthers as yellow dust, to be carried by insect or other vectors, including wind, to the ovary (stigma) of other flowers to produce the embryo enclosed by the seed. The pollens of many plants are allergenic. [NIH] Polyethylene: A vinyl polymer made from ethylene. It can be branched or linear. Branched or low-density polyethylene is tough and pliable but not to the same degree as linear polyethylene. Linear or high-density polyethylene has a greater hardness and tensile strength. Polyethylene is used in a variety of products, including implants and prostheses. [NIH]
Polyethylene Glycols: Alpha-Hydro-omega-hydroxypoly(oxy-1,2-ethanediyls). Additional polymers of ethylene oxide and water and their ethers. They vary in consistency from liquid to solid, depending on the molecular weight, indicated by a number following the name. Used as surfactants in industry, including foods, cosmetics and pharmaceutics; in biomedicine, as dispersing agents, solvents, ointment and suppository bases, vehicles, tablet excipients. Some specific groups are lauromagrogols, nonoxynols, octoxynols and poloxamers. [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] Polytherapy: A therapy which uses more than one drug. [EU] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postoperative: After surgery. [NIH] Post-translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potentiate: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Precursor: Something that precedes. In biological processes, a substance from which
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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] Prednisolone: A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states. [NIH] Prednisone: A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver. [NIH] 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 endpoint: The main result that is measured at the end of a study to see if a given treatment worked (e.g., the number of deaths or the difference in survival between the treatment group and the control group). What the primary endpoint will be is decided before the study begins. [NIH] Primary Prevention: Prevention of disease or mental disorders in susceptible individuals or populations through promotion of health, including mental health, and specific protection, as in immunization, as distinguished from the prevention of complications or after-effects of existing disease. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] 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] Prone: Having the front portion of the body downwards. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Propofol: A widely used anesthetic. [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] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed
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and unexposed groups. [NIH] Prostaglandins: A group of compounds derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway. They are extremely potent mediators of a diverse group of physiological processes. [NIH] Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Prosthesis: An artificial replacement of a part of the body. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protein 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] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Prothrombin: A plasma protein that is the inactive precursor of thrombin. It is converted to thrombin by a prothrombin activator complex consisting of factor Xa, factor V, phospholipid, and calcium ions. Deficiency of prothrombin leads to hypoprothrombinemia. [NIH]
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] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Pruritus: An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. [NIH]
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Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Psyllium: Dried, ripe seeds of Plantago psyllium, P. indica, and P. ovata (Plantaginaceae). Plantain seeds swell in water and are used as demulcents and bulk laxatives. [NIH] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]
Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary Edema: An accumulation of an excessive amount of watery fluid in the lungs, may be caused by acute exposure to dangerous concentrations of irritant gasses. [NIH] Pulmonary Embolism: Embolism in the pulmonary artery or one of its branches. [NIH] 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]
Purpura: Purplish or brownish red discoloration, easily visible through the epidermis, caused by hemorrhage into the tissues. [NIH] Purulent: Consisting of or containing pus; associated with the formation of or caused by pus. [EU] Putrefaction: The process of decomposition of animal and vegetable matter by living organisms. [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] Quercetin: Aglucon of quercetrin, rutin, and other glycosides. It is widely distributed in the plant kingdom, especially in rinds and barks, clover blossoms, and ragweed pollen. [NIH] Quinidine: An optical isomer of quinine, extracted from the bark of the Cinchona tree and similar plant species. This alkaloid dampens the excitability of cardiac and skeletal muscles by blocking sodium and potassium currents across cellular membranes. It prolongs cellular action potential, and decreases automaticity. Quinidine also blocks muscarinic and alphaadrenergic neurotransmission. [NIH] Quinine: An alkaloid derived from the bark of the cinchona tree. It is used as an antimalarial drug, and is the active ingredient in extracts of the cinchona that have been used for that purpose since before 1633. Quinine is also a mild antipyretic and analgesic and has been used in common cold preparations for that purpose. It was used commonly and as
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a bitter and flavoring agent, and is still useful for the treatment of babesiosis. Quinine is also useful in some muscular disorders, especially nocturnal leg cramps and myotonia congenita, because of its direct effects on muscle membrane and sodium channels. The mechanisms of its antimalarial effects are not well understood. [NIH] Quinones: Hydrocarbon rings which contain two ketone moieties in any position. They can be substituted in any position except at the ketone groups. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radioactive: Giving off radiation. [NIH] 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] 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] Radius: The lateral bone of the forearm. [NIH] Raloxifene: A second generation selective estrogen receptor modulator (SERM) used to prevent osteoporosis in postmenopausal women. It has estrogen agonist effects on bone and cholesterol metabolism but behaves as a complete estrogen antagonist on mammary gland and uterine tissue. [NIH] Random Allocation: A process involving chance used in therapeutic trials or other research endeavor for allocating experimental subjects, human or animal, between treatment and control groups, or among treatment groups. It may also apply to experiments on inanimate objects. [NIH] Randomization: Also called random allocation. Is allocation of individuals to groups, e.g., for experimental and control regimens, by chance. Within the limits of chance variation, random allocation should make the control and experimental groups similar at the start of an investigation and ensure that personal judgment and prejudices of the investigator do not influence allocation. [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
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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] Reabsorption: 1. The act or process of absorbing again, as the selective absorption by the kidneys of substances (glucose, proteins, sodium, etc.) already secreted into the renal tubules, and their return to the circulating blood. 2. Resorption. [EU] 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 in either parent; usually applied to linked genes. [EU] Recombinant Proteins: Proteins prepared by recombinant DNA technology. [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] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflux: The term used when liquid backs up into the esophagus from the stomach. [NIH] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] 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] Relative risk: The ratio of the incidence rate of a disease among individuals exposed to a specific risk factor to the incidence rate among unexposed individuals; synonymous with risk ratio. Alternatively, the ratio of the cumulative incidence rate in the exposed to the cumulative incidence rate in the unexposed (cumulative incidence ratio). The term relative risk has also been used synonymously with odds ratio. This is because the odds ratio and relative risk approach each other if the disease is rare ( 5 percent of population) and the number of subjects is large. [NIH] Reminder Systems: Systems used to prompt or aid the memory. The systems can be computerized reminders, color coding, telephone calls, or devices such as letters and postcards. [NIH] Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Renin: An enzyme which is secreted by the kidney and is formed from prorenin in plasma and kidney. The enzyme cleaves the Leu-Leu bond in angiotensinogen to generate angiotensin I. EC 3.4.23.15. (Formerly EC 3.4.99.19). [NIH] Renin-Angiotensin System: A system consisting of renin, angiotensin-converting enzyme, and angiotensin II. Renin, an enzyme produced in the kidney, acts on angiotensinogen, an alpha-2 globulin produced by the liver, forming angiotensin I. The converting enzyme
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contained in the lung acts on angiotensin I in the plasma converting it to angiotensin II, the most powerful directly pressor substance known. It causes contraction of the arteriolar smooth muscle and has other indirect actions mediated through the adrenal cortex. [NIH] Reperfusion: Restoration of blood supply to tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. It is primarily a procedure for treating infarction or other ischemia, by enabling viable ischemic tissue to recover, thus limiting further necrosis. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing reperfusion injury. [NIH] Reperfusion Injury: Functional, metabolic, or structural changes, including necrosis, in ischemic tissues thought to result from reperfusion to ischemic areas of the tissue. The most common instance is myocardial reperfusion injury. [NIH] Resolving: The ability of the eye or of a lens to make small objects that are close together, separately visible; thus revealing the structure of an object. [NIH] Resorption: The loss of substance through physiologic or pathologic means, such as loss of dentin and cementum of a tooth, or of the alveolar process of the mandible or maxilla. [EU] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Respiratory Physiology: Functions and activities of the respiratory tract as a whole or of any of its parts. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retinopathy: 1. Retinitis (= inflammation of the retina). 2. Retinosis (= degenerative, noninflammatory condition of the retina). [EU] 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] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Ribavirin: 1-beta-D-Ribofuranosyl-1H-1,2,4-triazole-3-carboxamide. A nucleoside antimetabolite antiviral agent that blocks nucleic acid synthesis and is used against both RNA and DNA viruses. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH]
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Rickets: A condition caused by deficiency of vitamin D, especially in infancy and childhood, with disturbance of normal ossification. The disease is marked by bending and distortion of the bones under muscular action, by the formation of nodular enlargements on the ends and sides of the bones, by delayed closure of the fontanelles, pain in the muscles, and sweating of the head. Vitamin D and sunlight together with an adequate diet are curative, provided that the parathyroid glands are functioning properly. [EU] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Risk patient: Patient who is at risk, because of his/her behaviour or because of the type of person he/she is. [EU] Rodent Control: The reduction or regulation of the population of noxious, destructive, or dangerous rodents through chemical, biological, or other means. [NIH] Rodenticides: Substances used to destroy or inhibit the action of rats, mice, or other rodents. [NIH]
Rutin: 3-((6-O-(6-Deoxy-alpha-L-mannopyranosyl)-beta-D-glucopyranosyl)oxy)-2-(3,4dihydroxyphenyl)-5,7-dihydroxy-4H-1-benzopyran-4-one. Found in many plants, including buckwheat, tobacco, forsythia, hydrangea, pansies, etc. It has been used therapeutically to decrease capillary fragility. [NIH] Salicylate: Non-steroidal anti-inflammatory drugs. [NIH] Salicylic: A tuberculosis drug. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Saphenous: Applied to certain structures in the leg, e. g. nerve vein. [NIH] Saphenous Vein: The vein which drains the foot and leg. [NIH] Scans: Pictures of structures inside the body. Scans often used in diagnosing, staging, and monitoring disease include liver scans, bone scans, and computed tomography (CT) or computerized axial tomography (CAT) scans and magnetic resonance imaging (MRI) scans. In liver scanning and bone scanning, radioactive substances that are injected into the bloodstream collect in these organs. A scanner that detects the radiation is used to create pictures. In CT scanning, an x-ray machine linked to a computer is used to produce detailed pictures of organs inside the body. MRI scans use a large magnet connected to a computer to create pictures of areas inside the body. [NIH] Schematic: Representative or schematic eye computed from the average of a large number of human eye measurements by Allvar Gullstrand. [NIH] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] 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
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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] Sediment: A precipitate, especially one that is formed spontaneously. [EU] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Selective estrogen receptor modulator: SERM. A drug that acts like estrogen on some tissues, but blocks the effect of estrogen on other tissues. Tamoxifen and raloxifene are SERMs. [NIH] 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] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sepsis: The presence of bacteria in the bloodstream. [NIH] Septal: An abscess occurring at the root of the tooth on the proximal surface. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Sequester: A portion of dead bone which has become detached from the healthy bone tissue, as occurs in necrosis. [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] Ships: Large vessels propelled by power or sail used for transportation on rivers, seas, oceans, or other navigable waters. Boats are smaller vessels propelled by oars, paddles, sail, or power; they may or may not have a deck. [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]
Shyness: Discomfort and partial inhibition of the usual forms of behavior when in the presence of others. [NIH] Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the
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brain. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]
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] 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] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Sperm: The fecundating fluid of the male. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spirochete: Lyme disease. [NIH] Squamous: Scaly, or platelike. [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]
Standard therapy: A currently accepted and widely used treatment for a certain type of cancer, based on the results of past research. [NIH] Steady state: Dynamic equilibrium. [EU] 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]
Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between
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the termination of the esophagus and the beginning of the duodenum. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Stroma: The middle, thickest layer of tissue in the cornea. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] 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] Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts. [NIH] Sudden death: Cardiac arrest caused by an irregular heartbeat. The term "death" is somewhat misleading, because some patients survive. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Surfactant: A fat-containing protein in the respiratory passages which reduces the surface tension of pulmonary fluids and contributes to the elastic properties of pulmonary tissue. [NIH]
Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synaptic Transmission: The communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. In chemical synaptic transmission, the presynaptic neuron releases a neurotransmitter that diffuses across the synaptic cleft and binds to specific synaptic receptors. These activated receptors modulate ion channels and/or secondmessenger systems to influence the postsynaptic cell. Electrical transmission is less common in the nervous system, and, as in other tissues, is mediated by gap junctions. [NIH] Synergistic: Acting together; enhancing the effect of another force or agent. [EU]
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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] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Teratogen: A substance which, through immediate, prolonged or repeated contact with the skin may involve a risk of subsequent non-hereditable birth defects in offspring. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Tetracycline: An antibiotic originally produced by Streptomyces viridifaciens, but used mostly in synthetic form. It is an inhibitor of aminoacyl-tRNA binding during protein synthesis. [NIH] Tetrahydronaphthalenes: Partially saturated 1,2,3,4-tetrahydronaphthalene compounds. [NIH]
Thalidomide: A pharmaceutical agent originally introduced as a non-barbiturate hypnotic, but withdrawn from the market because of its known tetratogenic effects. It has been reintroduced and used for a number of immunological and inflammatory disorders. Thalidomide displays immunosuppresive and anti-angiogenic activity. It inhibits release of tumor necrosis factor alpha from monocytes, and modulates other cytokine action. [NIH] Theophylline: Alkaloid obtained from Thea sinensis (tea) and others. It stimulates the heart and central nervous system, dilates bronchi and blood vessels, and causes diuresis. The drug is used mainly in bronchial asthma and for myocardial stimulation. Among its more prominent cellular effects are inhibition of cyclic nucleotide phosphodiesterases and antagonism of adenosine receptors. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] 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] 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.
Dictionary 233
[NIH]
Thrombopenia: Reduction in the number of platelets in the blood. [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] Thromboxanes: Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators of the actions of polyunsaturated fatty acids transformed by cyclooxygenase. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Thyrotropin: A peptide hormone secreted by the anterior pituitary. It promotes the growth of the thyroid gland and stimulates the synthesis of thyroid hormones and the release of thyroxine by the thyroid gland. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Ticlopidine: Ticlopidine is an effective inhibitor of platelet aggregation. The drug has been 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] Topical: On the surface of the body. [NIH] Torsion: A twisting or rotation of a bodily part or member on its axis. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or
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animals. [NIH] Tramadol: A narcotic analgesic proposed for severe pain. It may be habituating. [NIH] Transcriptase: An enzyme which catalyses the synthesis of a complementary mRNA molecule from a DNA template in the presence of a mixture of the four ribonucleotides (ATP, UTP, GTP and CTP). [NIH] 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] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Translocation: The movement of material in solution inside the body of the plant. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Trichomoniasis: An infection with the protozoan parasite Trichomonas vaginalis. [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] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] Tunica Intima: The innermost coat of blood vessels, consisting of a thin lining of endothelial cells longitudinally oriented and continuous with the endothelium of capillaries on the one hand and the endocardium of the heart on the other. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ubiquitin: A highly conserved 76 amino acid-protein found in all eukaryotic cells. [NIH] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Ulceration: 1. The formation or development of an ulcer. 2. An ulcer. [EU] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Uraemia: 1. An excess in the blood of urea, creatinine, and other nitrogenous end products of protein and amino acids metabolism; more correctly referred to as azotemia. 2. In current usage the entire constellation of signs and symptoms of chronic renal failure, including nausea, vomiting anorexia, a metallic taste in the mouth, a uraemic odour of the breath, pruritus, uraemic frost on the skin, neuromuscular disorders, pain and twitching in the muscles, hypertension, edema, mental confusion, and acid-base and electrolyte imbalances.
Dictionary 235
[EU]
Urea: A compound (CO(NH2)2), formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. [NIH] Uremia: The illness associated with the buildup of urea in the blood because the kidneys are not working effectively. Symptoms include nausea, vomiting, loss of appetite, weakness, and mental confusion. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]
Uric: A kidney stone that may result from a diet high in animal protein. When the body breaks down this protein, uric acid levels rise and can form stones. [NIH] Urinalysis: Examination of urine by chemical, physical, or microscopic means. Routine urinalysis usually includes performing chemical screening tests, determining specific gravity, observing any unusual color or odor, screening for bacteriuria, and examining the sediment microscopically. [NIH] Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [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] Urticaria: A vascular reaction of the skin characterized by erythema and wheal formation due to localized increase of vascular permeability. The causative mechanism may be allergy, infection, or stress. [NIH] Uvea: The middle coat of the eyeball, consisting of the choroid in the back of the eye and the ciliary body and iris in the front of the eye. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vaginal: Of or having to do with the vagina, the birth canal. [NIH] Valves: Flap-like structures that control the direction of blood flow through the heart. [NIH] Varicose: The common ulcer in the lower third of the leg or near the ankle. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vascular Resistance: An expression of the resistance offered by the systemic arterioles, and to a lesser extent by the capillaries, to the flow of blood. [NIH] Vasculitis: Inflammation of a blood vessel. [NIH] Vasoactive: Exerting an effect upon the calibre of blood vessels. [EU] Vasodilator: An agent that widens blood vessels. [NIH] Vasomotor: 1. Affecting the calibre of a vessel, especially of a blood vessel. 2. Any element or agent that effects the calibre of a blood vessel. [EU] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venereal: Pertaining or related to or transmitted by sexual contact. [EU] Venous: Of or pertaining to the veins. [EU] Venous Thrombosis: The formation or presence of a thrombus within a vein. [NIH]
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Ventilation: 1. In respiratory physiology, the process of exchange of air between the lungs and the ambient air. Pulmonary ventilation (usually measured in litres per minute) refers to the total exchange, whereas alveolar ventilation refers to the effective ventilation of the alveoli, in which gas exchange with the blood takes place. 2. In psychiatry, verbalization of one's emotional problems. [EU] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Ventricular Dysfunction: A condition in which the ventricles of the heart exhibit a decreased functionality. [NIH] Ventricular fibrillation: Rapid, irregular quivering of the heart's ventricles, with no effective heartbeat. [NIH] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Verapamil: A calcium channel blocker that is a class IV anti-arrhythmia agent. [NIH] Vertebrae: A bony unit of the segmented spinal column. [NIH] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Vindesine: Vinblastine derivative with antineoplastic activity against acute leukemia, lung cancer, carcinoma of the breast, squamous cell carcinoma of the esophagus, head, and neck, and Hodgkin's and non-Hodgkin's lymphomas. Major side effects are myelosuppression and neurotoxicity. Vindesine is used extensively in chemotherapy protocols. [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] Vitamin D: The vitamin that mediates intestinal calcium absorption, bone calcium metabolism, and probably muscle activity. It usually acts as a hormone precursor, requiring 2 stages of metabolism before reaching actual hormonal form. It is isolated from fish liver oils and used in the treatment and prevention of rickets. [NIH] Vitamin K: A substance that promotes the clotting of blood. [NIH] Vitreoretinal: A rare familial condition characterized by a clear vitreous, except for preretinal filaments and veils which have been loosened from the retina, a dense hyaloid membrane which is perforated and detached, and masses of peripheral retinal pigmentation inters. [NIH] Vitreous Hemorrhage: Hemorrhage into the vitreous body. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH]
Dictionary 237
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] Watchful waiting: Closely monitoring a patient's condition but withholding treatment until symptoms appear or change. Also called observation. [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]
Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] 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]
239
INDEX 2 2-Propanol, 130, 131, 132, 137, 138, 175, 177 A Abdomen, 175, 184, 207, 209, 218, 230 Abdominal, 45, 164, 175, 185, 200, 217, 218 Abdominal Pain, 164, 175, 200 Abscess, 175, 199, 229 Absolute risk, 23, 175 ACE, 7, 35, 127, 134, 175 Acetaminophen, 57, 175 Acetone, 175 Acidosis, 68, 175 Acute leukemia, 175, 236 Acute renal, 19, 175 Adamantane, 10, 175 Adenocarcinoma, 175, 203 Adenosine, 175, 177, 185, 219, 232 Adjustment, 30, 31, 104, 175 Adolescence, 175, 218 Adrenal Cortex, 175, 192, 222, 227 Adrenergic, 176, 177, 181, 197, 212, 222, 224 Adverse Effect, 4, 20, 28, 176, 229 Affinity, 9, 126, 176, 230 Afterload, 33, 176 Agar, 176, 205, 220 Agarose, 176, 205 Age-Adjusted, 47, 176 Agonist, 176, 215, 225 Albumin, 48, 51, 52, 53, 55, 68, 73, 78, 90, 176, 212, 220, 229 Alertness, 176, 185 Algorithms, 176, 183 Alimentary, 176, 217 Alkaline, 127, 175, 176, 183, 185 Alkaloid, 176, 215, 224, 232 Alleles, 16, 26, 177 Alpha Particles, 177, 225 Alprenolol, 177, 212 Alternative medicine, 97, 114, 148, 177, 190 Alveolar Process, 177, 227 Alveoli, 177, 236 Amebiasis, 177, 212 Amine, 177, 204 Amino Acid Sequence, 177, 179, 198
Amino Acids, 177, 197, 218, 221, 223, 227, 234, 235 Amiodarone, 49, 76, 90, 177 Amoxicillin, 83, 177 Ampicillin, 177 Amplification, 13, 177 Amyloid, 147, 177 Anaesthesia, 98, 178, 206 Analgesic, 175, 178, 205, 224, 234 Analog, 178, 199 Analogous, 10, 178, 220, 234 Analytes, 8, 9, 178 Anaphylatoxins, 178, 190 Anaphylaxis, 143, 178 Anatomical, 178, 182, 206, 217 Androgens, 175, 178, 192 Anemia, 4, 143, 178 Anesthesia, 49, 178, 182, 196 Angina, 125, 129, 146, 178, 179, 212, 222 Angina Pectoris, 178, 212, 222 Angiography, 30, 31, 64, 178, 187, 210 Angiopathy, 147, 178 Angioplasty, 40, 89, 178, 182 Animal model, 22, 37, 178 Anionic, 8, 179 Anions, 176, 179, 207, 229 Anorexia, 179, 200, 234 Antagonism, 103, 106, 179, 185, 232 Anthraquinones, 137, 179 Antiallergic, 179, 192 Antianginal, 177, 179 Antiarrhythmic, 177, 179 Antibiotic, 25, 134, 177, 179, 185, 189, 197, 218, 232 Antibodies, 6, 32, 126, 149, 179, 180, 202, 205, 210, 213, 220 Antibodies, Anticardiolipin, 179, 180 Antibodies, Antiphospholipid, 179, 180 Antibody, 44, 125, 126, 149, 176, 179, 180, 190, 202, 204, 205, 206, 213, 225, 230 Anticonvulsants, 19, 179 Antidiabetic, 69, 179 Antidiabetic Agent, 69, 179 Antifungal, 179, 199, 212 Antigen, 100, 104, 126, 176, 178, 179, 180, 190, 204, 205, 206 Antigen-Antibody Complex, 180, 190 Antihypertensive, 177, 180, 204
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Anti-infective, 180, 185 Anti-inflammatory, 175, 180, 181, 187, 192, 201, 205, 206, 212, 222, 228 Anti-Inflammatory Agents, 180, 181, 187, 192 Antimetabolite, 180, 199, 227 Antimicrobial, 180, 189, 195 Antineoplastic, 180, 186, 192, 199, 220, 236 Antioxidant, 25, 180, 217 Antiphospholipid Syndrome, 73, 89, 149, 179, 180 Antipruritic, 180, 185, 188 Antipyretic, 175, 180, 224 Antiseptic, 175, 180, 186 Antithrombotic, 30, 70, 129, 146, 180, 204, 233 Antiviral, 180, 227 Anus, 180, 184, 203, 218 Aorta, 180, 192, 202, 236 Aortic Valve, 81, 105, 180 Apolipoproteins, 180, 209 Apoptosis, 25, 37, 180 Aqueous, 181, 183, 193, 208 Arachidonate 12-Lipoxygenase, 181, 209 Arachidonate 15-Lipoxygenase, 181, 209 Arachidonate Lipoxygenases, 181, 209 Arachidonic Acid, 14, 181, 208, 223 Arrhythmia, 179, 181, 236 Arterial, 7, 13, 14, 22, 40, 53, 119, 125, 180, 181, 186, 188, 205, 208, 223, 232, 234 Arteries, 6, 22, 31, 32, 40, 178, 180, 181, 184, 192, 202, 207, 210, 212, 214, 233 Arterioles, 181, 184, 186, 214, 235 Arteriosclerosis, 181, 205, 214, 233 Arteriovenous, 4, 181, 233 Arteriovenous Fistula, 4, 181, 233 Arthroplasty, 50, 52, 54, 59, 76, 88, 181 Aspirin, 6, 7, 25, 31, 33, 38, 39, 40, 42, 44, 47, 50, 51, 53, 57, 70, 79, 81, 83, 85, 88, 90, 91, 97, 109, 118, 119, 125, 129, 146, 147, 150, 181 Assay, 9, 32, 73, 126, 129, 181 Astringent, 181, 186 Asymptomatic, 76, 177, 181, 217 Atenolol, 28, 33, 181 Atherectomy, 182, 196 Atmospheric Pressure, 131, 138, 182 Atrium, 182, 236 Atypical, 16, 22, 182 Autacoids, 182, 206 Autodigestion, 182, 217 Autosuggestion, 182, 205
Axillary, 182, 184 Axillary Artery, 182, 184 Azotemia, 182, 234 B Babesiosis, 182, 225 Bacteria, 137, 179, 180, 182, 189, 191, 196, 197, 198, 212, 220, 229, 235 Bacterial Infections, 182, 187, 209 Bacteriophage, 182, 220 Bacterium, 182, 191, 198 Bacteriuria, 182, 235 Barbiturate, 182, 232 Barium, 127, 183 Base, 17, 19, 20, 69, 132, 183, 193, 198, 208, 232, 234 Benign, 183, 202, 225 Benzbromarone, 16, 183 Benzene, 10, 183 Beta-pleated, 177, 183 Bilateral, 65, 183 Bile, 183, 188, 199, 200, 209 Bile Acids, 183, 200 Biliary, 183, 188, 217 Biliary Tract, 183, 217 Bilirubin, 176, 183 Binding agent, 9, 183 Binding Sites, 127, 183 Bioavailability, 4, 11, 127, 183 Biochemical, 12, 24, 51, 53, 61, 98, 125, 177, 180, 183, 200 Biopsy, 183, 218 Biosynthesis, 36, 104, 181, 183 Biotechnology, 41, 42, 142, 148, 159, 183 Biotransformation, 183, 218 Bladder, 115, 184, 207, 223, 235 Blood Coagulation, 11, 12, 37, 55, 78, 126, 184, 185, 207, 232, 233 Blood Coagulation Factors, 184 Blood Coagulation Tests, 184, 207 Blood Platelets, 184, 232 Blood pressure, 15, 35, 180, 184, 186, 205, 213, 230 Body Fluids, 184, 185, 230 Bone Marrow, 175, 183, 184, 205, 210, 213, 214 Bone Resorption, 37, 184 Bone scan, 184, 228 Bowel, 164, 184, 194, 206, 207, 218 Bowel Movement, 184, 194 Brachial, 15, 184 Brachial Artery, 15, 184 Brachytherapy, 184, 207, 225
Index 241
Bradykinin, 184, 220 Branch, 171, 184, 217, 218, 219, 224, 230, 232 Breakdown, 184, 194, 200 Broad-spectrum, 177, 185 Bromine, 124, 185 Bronchi, 185, 197, 232 Bronchial, 185, 204, 232 Buccal, 185, 204, 210 Bypass, 47, 185, 192, 233 C Caesarean section, 98, 185 Caffeine, 165, 185 Calcification, 22, 85, 181, 185 Calcium, 12, 22, 70, 126, 185, 190, 212, 223, 236 Calcium channel blocker, 185, 236 Callus, 185, 196 Camphor, 10, 185 Candidiasis, 185, 199 Capecitabine, 45, 48, 185 Capillary, 8, 107, 134, 184, 186, 228, 236 Capsules, 186, 195 Captopril, 33, 186 Carbohydrate, 126, 186, 192, 201, 221 Carboplatin, 100, 186 Carcinogen, 186, 212 Carcinogenic, 183, 186, 206 Carcinoma, 78, 126, 186, 203, 236 Cardiomyopathy, 119, 186 Cardioselective, 181, 186, 222 Cardiotonic, 186, 194 Cardiovascular, 12, 15, 18, 34, 48, 64, 71, 76, 89, 107, 119, 125, 136, 142, 186, 208 Cardiovascular disease, 13, 35, 136, 143, 186 Cardioversion, 54, 81, 186 Carrier Proteins, 186, 220 Case report, 3, 25, 43, 45, 68, 98, 186 Cataract, 56, 84, 186 Catechol, 56, 186 Catheterization, 64, 178, 186 Catheters, 13, 44, 67, 118, 147, 187, 206, 207 Cations, 187, 207 Celecoxib, 63, 71, 147, 187 Cell Cycle, 37, 187, 198 Cell Death, 180, 187, 198, 214 Cell Division, 182, 187, 198, 213, 219 Cell membrane, 186, 187, 219 Cellulose, 187, 219
Central Nervous System, 80, 183, 185, 187, 199, 201, 202, 208, 232 Central Nervous System Infections, 187, 202 Centrifugation, 187, 212 Cerebral, 57, 69, 118, 125, 147, 187, 197, 210, 234 Cerebral Angiography, 187, 210 Cerebrovascular, 14, 125, 129, 186, 187 Cerebrum, 187 Check-up, 6, 187 Chelation, 62, 101, 187 Chelation Therapy, 62, 101, 187 Chemotactic Factors, 188, 190 Chemotherapy, 69, 97, 98, 100, 103, 104, 119, 143, 188, 189, 236 Chiropractic, 104, 188 Chlorine, 124, 188 Chloroform, 124, 188 Cholesterol, 35, 108, 183, 188, 192, 195, 204, 209, 210, 225 Cholesterol Esters, 188, 209 Cholestyramine, 53, 188 Cholinergic, 188, 215 Chondroitin sulfate, 93, 188 Chromatin, 181, 188 Chromosomal, 177, 188, 200, 220 Chromosome, 37, 188, 191, 198, 202 Chronic Disease, 5, 188 Chronic Fatigue Syndrome, 136, 188 Chronic renal, 188, 199, 234 Chylomicrons, 188, 209 Cinchona, 188, 224 Ciprofloxacin, 164, 189 Clarithromycin, 79, 189 Clinical Medicine, 189, 222 Clinical trial, 5, 7, 13, 14, 21, 25, 35, 38, 39, 40, 117, 118, 120, 159, 189, 191, 192, 223, 225 Cloning, 183, 189, 209 Clot Retraction, 189, 220 Coal, 183, 189 Coenzyme, 18, 55, 99, 110, 189 Cofactor, 36, 189, 223, 232, 233 Cognition, 18, 25, 189 Colitis, 189, 206 Collagen, 32, 82, 90, 189, 191, 220, 222 Collapse, 178, 184, 189 Colloidal, 32, 176, 189, 196, 229 Colorectal, 45, 78, 189 Combination chemotherapy, 119, 189 Combination Therapy, 44, 57, 97, 190, 197
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Complement, 128, 178, 190, 220 Complementary and alternative medicine, 97, 114, 190 Complementary medicine, 97, 190 Computational Biology, 159, 190 Computed tomography, 190, 228 Computer Simulation, 9, 190 Computerized axial tomography, 190, 228 Conception, 191, 199, 211 Concomitant, 54, 146, 191 Confounding, 26, 34, 191 Confusion, 191, 234, 235 Congenita, 191, 225 Congestive heart failure, 18, 191, 209 Conjugated, 191, 193 Conjugation, 184, 191, 198 Connective Tissue, 180, 184, 189, 191, 199, 227, 232 Connective Tissue Diseases, 180, 191 Consciousness, 178, 191, 195 Constriction, 118, 191, 207 Consultation, 4, 191 Consumption, 5, 191, 200, 227 Contraception, 41, 191, 209 Contractility, 191, 195 Contraindications, ii, 4, 191 Contrast Media, 191, 210 Control group, 191, 222, 225 Controlled study, 50, 192 Coordination, 8, 19, 192 Corn Oil, 133, 192 Coronary, 13, 34, 47, 89, 119, 125, 129, 148, 178, 186, 192, 212, 214, 233 Coronary Artery Bypass, 47, 192 Coronary Disease, 34, 192 Coronary heart disease, 186, 192 Coronary Thrombosis, 192, 212, 214 Coronary Vessels, 192 Cortical, 192, 198, 229 Corticosteroid, 43, 192, 222 Cortisol, 176, 192 Cortisone, 192, 222 Coumarin, 17, 78, 124, 127, 134, 192 Cranial, 192, 202 Craniocerebral Trauma, 192, 202 Creatinine, 192, 234 Critical Care, 14, 27, 193 Curative, 193, 228, 232 Cutaneous, 51, 52, 72, 74, 81, 185, 193, 210 Cyclic, 108, 125, 185, 193, 232 Cytochrome, 9, 10, 14, 16, 22, 25, 26, 27, 52, 58, 60, 61, 73, 75, 79, 99, 100, 104, 193
Cytokine, 15, 193, 232 Cytoplasm, 181, 187, 193, 213, 227 D Data Collection, 19, 193, 199 Databases, Bibliographic, 159, 193 Decarboxylation, 193, 204 Degenerative, 193, 203, 210, 227 Deletion, 180, 193 Delivery of Health Care, 193, 202 Density, 39, 133, 187, 193, 195, 209, 210, 216, 221 Depressive Disorder, 193, 209 Detoxification, 10, 134, 193 Deuterium, 10, 193, 204 Diabetes Insipidus, 194, 204 Diabetes Mellitus, 143, 194, 201, 203 Diabetic Retinopathy, 68, 194, 219 Diagnostic Errors, 194, 211 Diagnostic procedure, 123, 148, 194 Dialyzer, 194, 203 Diarrhea, 53, 101, 164, 177, 188, 194, 219 Diastolic, 194, 205 Diffusion, 194, 202, 205 Digestion, 176, 183, 184, 194, 207, 209, 230 Digestive system, 121, 194, 200 Digitalis, 33, 194 Dihydrotestosterone, 194, 226 Dihydroxy, 14, 194, 228 Dilatation, 178, 194, 222 Diploid, 194, 219 Dipyridamole, 45, 98, 110, 194 Direct, iii, 17, 25, 37, 82, 126, 135, 151, 186, 189, 194, 200, 204, 225, 226 Disinfectant, 175, 194 Disposition, 11, 16, 62, 194 Dissociation, 9, 126, 176, 194, 207 Dissociative Disorders, 194, 195 Distal, 192, 195, 200, 223 Diuresis, 185, 195, 232 Diuretic, 195, 199, 204 Dosage Forms, 130, 195 Doxycycline, 48, 195 Drug Interactions, 3, 8, 16, 21, 22, 25, 26, 79, 135, 152, 195 Duodenum, 183, 195, 217, 231 Dyes, 177, 195, 215 Dyslipidemia, 18, 195 Dyspareunia, 195, 197 Dystrophy, 98, 195, 214 E Edema, 108, 188, 194, 195, 199, 204, 224, 234
Index 243
Effector, 22, 190, 195 Efficacy, 11, 15, 20, 26, 27, 28, 30, 35, 43, 47, 56, 57, 73, 100, 117, 130, 131, 133, 195 Ejection fraction, 119, 195 Elastin, 22, 189, 191, 195 Elective, 81, 195 Electrocoagulation, 189, 195 Electrolyte, 192, 196, 212, 221, 230, 234 Electrons, 180, 183, 196, 207, 217, 225 Electrophoresis, 8, 196, 205, 208 Electroplating, 186, 196 Emboli, 119, 196, 237 Embolism, 35, 38, 50, 69, 146, 164, 196, 224, 237 Embolization, 196, 237 Embolus, 28, 196, 206 Embryo, 37, 196, 199, 206, 221 Embryogenesis, 37, 196 Empiric, 27, 196 Empirical, 16, 196 Enalapril, 33, 196 Endarterectomy, 38, 178, 182, 196 Endometriosis, 196, 209, 215 Endophthalmitis, 64, 196 Endothelial cell, 11, 32, 45, 98, 196, 232, 234 Endothelium, 14, 196, 197, 220, 234 Endothelium, Lymphatic, 196, 197 Endothelium, Vascular, 196, 197 Endotoxic, 197, 209 Endotoxin, 13, 197, 234 Enoxaparin, 43, 55, 75, 88, 142, 197 Environmental Health, 158, 160, 197 Enzymatic, 10, 57, 136, 185, 190, 197, 199, 204, 227 Enzyme Inhibitors, 197, 220 Epidemiological, 7, 197 Epidural, 43, 49, 77, 90, 197 Epinephrine, 176, 197, 234 Epithelium, 196, 197, 200 Erythrocytes, 178, 182, 184, 197 Erythromycin, 189, 197 Esophagus, 149, 194, 197, 200, 203, 210, 219, 226, 231, 236 Estrogen, 12, 197, 225, 229 Estrogen Replacement Therapy, 12, 197 Ether, 128, 198 Ethnic Groups, 28, 198 Etoposide, 100, 106, 198 Eukaryotic Cells, 198, 234 Excipients, 198, 221 Excitability, 198, 224
Excitatory, 198, 201 Exhaustion, 179, 198 Exogenous, 183, 186, 198 Exon, 52, 60, 198 External-beam radiation, 198, 225 Extracellular, 177, 191, 198, 230 Extraction, 8, 9, 48, 74, 83, 88, 198 Extravasation, 198, 203 Extremity, 67, 198, 208 F F Factor, 104, 125, 198 Family Planning, 159, 198 Fat, 178, 181, 184, 192, 196, 198, 209, 227, 231 Fatigue, 136, 188, 198, 202 Fatty acids, 176, 198, 201, 209, 223, 233 Feces, 124, 198 Fetal Development, 37, 199 Fetus, 37, 199, 222 Fibrin, 13, 15, 136, 184, 189, 199, 220, 232, 233 Fibrinogen, 11, 13, 136, 199, 220, 223, 232 Fibrinolytic, 11, 13, 199 Fistulas, 4, 164, 199, 233 Flatus, 199, 200 Fluconazole, 64, 77, 90, 199 Fluorouracil, 64, 69, 98, 146, 194, 199 Flutter, 81, 199 Focus Groups, 5, 199 Fold, 12, 199 Food Technology, 199, 212 Foramen, 64, 199, 218 Forearm, 184, 199, 225 Fungi, 179, 191, 196, 199, 212, 237 Furosemide, 33, 199 G Gallbladder, 175, 183, 194, 199, 200 Gamma Rays, 199, 225 Ganglia, 199, 215 Gangrene, 82, 83, 199 Gas, 8, 188, 194, 199, 200, 204, 215, 236 Gas exchange, 200, 236 Gasoline, 183, 200 Gastric, 129, 177, 182, 195, 200, 203, 204 Gastric Acid, 177, 200 Gastric Mucosa, 129, 200 Gastrin, 200, 204 Gastritis, 5, 200 Gastroenteritis, 185, 200 Gastroenterology, 164, 200 Gastroesophageal Reflux, 149, 200
244
Warfarin
Gastrointestinal, 4, 101, 127, 129, 184, 189, 197, 200, 208, 231 Gastrointestinal tract, 127, 200, 209 Gene, 15, 24, 26, 28, 36, 37, 42, 69, 75, 136, 142, 177, 183, 200, 208, 209 Genetic Techniques, 27, 200 Genetics, 10, 26, 191, 200, 218 Genital, 189, 200 Genotype, 8, 14, 15, 16, 26, 71, 200, 219 Giardiasis, 200, 212 Ginger, 102, 111, 200 Ginseng, 81, 102, 103, 105, 109, 111, 112, 113, 200 Gland, 175, 192, 201, 204, 217, 219, 223, 225, 229, 233 Glomerular, 201, 226 Glucocorticoid, 201, 222 Glucose, 179, 187, 194, 201, 203, 226 Glucose Intolerance, 194, 201 Glucuronic Acid, 201, 203 Glutamate, 37, 201 Glutamic Acid, 127, 201, 222 Glycerol, 201, 219 Glycerophospholipids, 201, 219 Glycols, 128, 201, 221 Glycoprotein, 11, 125, 199, 201, 232, 234 Glycosaminoglycan, 188, 201 Glycoside, 201, 204 Gout, 183, 201 Governing Board, 201, 221 Grade, 138, 202 Grafting, 192, 202 H Haematoma, 43, 77, 90, 202 Haemodialysis, 44, 202 Haemorrhage, 75, 77, 79, 202 Haploid, 202, 219 Haptens, 176, 202 Headache, 165, 185, 202 Headache Disorders, 202 Health Care Costs, 16, 26, 202 Health Expenditures, 202 Health Services, iv, 4, 19, 160, 193, 202 Heart attack, 47, 186, 202 Heart failure, 6, 18, 27, 35, 119, 191, 202, 209 Heart Transplantation, 33, 202 Heart Valves, 18, 46, 59, 76, 202 Heartbeat, 202, 231, 236 Heartburn, 149, 203 Hematology, 55, 58, 73, 82, 83, 88, 143, 203 Hematoma, 14, 15, 45, 74, 104, 203
Heme, 10, 183, 193, 203 Hemodialysis, 4, 44, 146, 194, 203 Hemoglobin, 178, 197, 203 Hemorrhage, 4, 14, 15, 25, 40, 61, 72, 82, 90, 147, 192, 194, 195, 202, 203, 224, 231, 236 Hemorrhaging, 131, 203 Hemorrhoid, 203, 233 Hemostasis, 4, 24, 30, 32, 37, 56, 125, 126, 142, 203, 207 Heparin, 35, 43, 49, 50, 58, 60, 64, 67, 70, 75, 82, 88, 89, 105, 111, 128, 136, 203 Hepatic, 11, 36, 99, 100, 101, 176, 203 Hepatitis, 5, 60, 203 Hepatocellular, 126, 203 Hepatocellular carcinoma, 126, 203 Hepatocytes, 203 Heredity, 200, 203 Heterogeneity, 176, 203 Heterotropic, 22, 203 Hirudin, 128, 204 Histamine, 149, 178, 204 Histidine, 17, 204 Homogeneous, 24, 204, 218 Homologous, 177, 204, 231 Hormonal, 192, 197, 204, 236 Hormone, 9, 192, 197, 200, 204, 209, 222, 232, 233, 236 Host, 182, 198, 204, 205, 208, 236 Hydralazine, 33, 204 Hydrochlorothiazide, 33, 204 Hydrogen, 175, 177, 183, 186, 193, 204, 209, 213, 215, 217, 223 Hydrolases, 134, 204, 218, 219 Hydrolysis, 184, 204, 218, 219, 221, 223 Hydrophilic, 128, 204 Hydrophobic, 8, 10, 201, 204, 209 Hydroxylation, 9, 104, 204 Hydroxylysine, 189, 204 Hydroxyproline, 189, 204 Hypercholesterolemia, 195, 204 Hyperlipidemia, 195, 204 Hypersensitivity, 60, 61, 178, 205, 208 Hypertension, 7, 14, 108, 186, 196, 202, 204, 205, 209, 212, 222, 234 Hypertriglyceridemia, 195, 205 Hypnotic, 182, 205, 232 Hypoplasia, 51, 205 Hypothyroidism, 143, 205 I Iatrogenic, 20, 205 Ibuprofen, 55, 205
Index 245
Id, 91, 107, 165, 170, 172, 205 Idiopathic, 29, 30, 31, 42, 205 Imidazole, 204, 205, 212 Immune response, 179, 192, 202, 205, 206, 231, 236 Immunization, 205, 222 Immunodiffusion, 176, 205 Immunoelectrophoresis, 99, 176, 205 Immunogenic, 205, 209 Immunoglobulin, 179, 205, 213 Immunologic, 13, 188, 205, 225 Immunology, 176, 206 Immunosuppressant, 199, 206 Impairment, 23, 206, 211 Implant radiation, 206, 207, 225 In situ, 150, 206 In vitro, 11, 13, 16, 22, 33, 37, 62, 73, 77, 206 In vivo, 10, 15, 22, 24, 33, 37, 203, 206, 233 Incision, 185, 206, 207 Incompetence, 200, 206 Indicative, 141, 206, 217, 235 Indomethacin, 146, 206 Induction, 26, 101, 178, 206 Infection, 5, 165, 175, 177, 182, 185, 188, 200, 206, 210, 215, 218, 231, 234, 235, 237 Inflammation, 176, 180, 181, 189, 196, 200, 203, 206, 208, 211, 217, 227, 230, 232, 233, 235 Inflammatory bowel disease, 164, 206 Infusion, 13, 22, 44, 206, 212 Ingestion, 206, 220 Inhalation, 206, 212, 220 Initiation, 15, 26, 47, 48, 49, 78, 206, 209 Inotropic, 181, 206 Insight, 36, 37, 206 Interindividual, 10, 16, 27, 63, 207 Intermittent, 207, 210, 218 Internal radiation, 207, 225 International Normalized Ratio, 4, 20, 49, 54, 55, 56, 64, 69, 70, 71, 81, 82, 84, 207 Interstitial, 184, 207, 226 Intestinal, 207, 236 Intestine, 164, 184, 195, 200, 204, 207, 208, 226, 230 Intoxication, 207, 237 Intracellular, 28, 32, 33, 134, 185, 200, 206, 207, 221 Intramuscular, 207, 217 Intraocular, 64, 196, 207 Intravascular, 62, 207 Intravenous, 43, 57, 106, 206, 207, 212, 217
Intravesical, 82, 90, 207 Intrinsic, 176, 207 Invasive, 65, 207, 210 Involuntary, 199, 207, 214 Ionization, 8, 207 Ionizing, 177, 207, 211, 225 Ions, 126, 127, 183, 188, 194, 196, 204, 207, 208, 223 Ischemia, 125, 178, 192, 207, 214, 227 Ischemic stroke, 6, 14, 26, 31, 38, 39, 40, 44, 50, 75, 91, 145, 147, 207 Isoelectric, 22, 208 Isoelectric Focusing, 22, 208 Isoelectric Point, 208 Isopropyl, 132, 208 Isozymes, 99, 208 J Joint, 50, 59, 76, 88, 181, 189, 208, 231, 232 K Kb, 158, 208 Keto, 127, 208 Kidney Disease, 56, 121, 143, 158, 208 Kinetic, 22, 207, 208 L Labile, 190, 208 Large Intestine, 194, 207, 208, 226, 230 Latent, 208, 222 Leg Ulcer, 11, 208 Lens, 186, 191, 208, 227 Lesion, 38, 192, 208, 234 Lethal, 27, 208 Lethargy, 205, 208 Leukemia, 97, 103, 104, 143, 175, 208, 236 Leukocytes, 184, 188, 206, 208, 213, 234 Leukotrienes, 181, 208 Levofloxacin, 55, 209 Levonorgestrel, 41, 209, 215 Library Services, 170, 209 Ligament, 209, 223 Ligands, 9, 17, 209 Ligase, 38, 209 Lipid, 35, 36, 106, 180, 181, 201, 208, 209, 217 Lipid A, 106, 209 Lipid Peroxidation, 209, 217 Lipopolysaccharides, 209 Lipoprotein, 136, 195, 209, 210 Lipoxygenase, 36, 181, 208, 209 Lisinopril, 33, 209 Lithium, 138, 164, 209 Liver cancer, 5, 209 Liver scan, 209, 228
246
Warfarin
Loading dose, 78, 209 Localized, 32, 202, 203, 206, 209, 219, 220, 233, 234, 235 Locomotion, 209, 219 Long-Term Care, 72, 147, 210 Loop, 17, 210 Low-density lipoprotein, 195, 209, 210 Lower Esophageal Sphincter, 200, 210 Lumen, 32, 37, 197, 210 Lupus, 149, 179, 180, 210, 232 Lymph, 182, 196, 197, 210 Lymphatic, 196, 197, 206, 210 Lymphocyte, 180, 210 Lymphoid, 179, 210 M Macula, 210 Macula Lutea, 210 Macular Degeneration, 65, 210 Magnetic Resonance Angiography, 31, 210 Magnetic Resonance Imaging, 210, 228 Malignancy, 13, 35, 210 Malignant, 175, 180, 209, 210, 225 Malnutrition, 176, 210 Mammary, 192, 210, 225 Mammogram, 185, 210, 212 Mandible, 177, 211, 227 Manic, 209, 211 Man-made, 186, 211 Maternal Exposure, 37, 211 Medical Errors, 19, 211 Medical Records, 8, 211 Medication Errors, 18, 19, 23, 25, 211 MEDLINE, 159, 211 Melanin, 211, 219, 234 Memory, 179, 211, 226 Meningeal, 104, 211 Meninges, 187, 192, 211 Meningitis, 199, 211 Mental Disorders, 121, 211, 222, 224 Mental Health, iv, 4, 121, 158, 160, 211, 216, 222, 224 Mental Processes, 194, 211, 224 Mentors, 14, 26, 211 Mercaptopurine, 54, 211 Meta-Analysis, 76, 142, 211 Metabolic disorder, 143, 194, 201, 212 Metabolite, 14, 183, 212 Metastasis, 212 Metastatic, 78, 212 Methyl salicylate, 106, 212 Methylene Chloride, 124, 212
Methyltransferase, 56, 212 Metoprolol, 33, 212 Metronidazole, 134, 164, 212 MI, 13, 147, 173, 212 Micelle, 8, 212 Miconazole, 42, 63, 68, 147, 212 Microbe, 212, 233 Microbiology, 182, 212 Microcalcifications, 185, 212 Microorganism, 137, 189, 212, 236 Microscopy, 32, 212 Microsomal, 33, 98, 100, 212 Mineralization, 37, 212 Mineralocorticoids, 175, 192, 212 Mitochondrial Swelling, 213, 214 Mitosis, 181, 213 Mitotic, 198, 213 Mobility, 17, 213 Mobilization, 198, 213 Modification, 32, 36, 37, 126, 213, 224 Molecule, 23, 180, 183, 188, 189, 190, 194, 195, 201, 204, 213, 217, 220, 225, 226, 231, 234 Monitor, 19, 40, 74, 193, 213, 215 Monoclonal, 32, 125, 213, 225 Monoclonal antibodies, 32, 213 Monocytes, 208, 213, 232 Morphological, 196, 213 Morphology, 186, 203, 213 Motility, 206, 213 Motion Sickness, 213, 214 Mucosa, 200, 210, 213 Muscular Dystrophies, 195, 213 Musculoskeletal System, 213, 216 Mutagenesis, 17, 23, 73, 213 Mutagens, 214 Myelosuppression, 214, 236 Myocardial Ischemia, 178, 192, 214 Myocardium, 178, 212, 214 Myotonia, 214, 225 Myotonic Dystrophy, 98, 214 N Narcotic, 212, 214, 234 Nausea, 108, 164, 195, 200, 214, 234, 235 NCI, 1, 119, 120, 157, 214 Necrosis, 58, 59, 60, 85, 89, 106, 146, 180, 196, 206, 212, 214, 227, 229, 232, 234 Need, 3, 6, 7, 12, 29, 63, 69, 129, 136, 138, 142, 149, 153, 166, 188, 214 Nephrology, 4, 43, 44, 214 Nephropathy, 43, 208, 214 Nephrotoxic, 19, 214
Index 247
Nerve, 25, 176, 178, 188, 214, 216, 227, 228 Nervous System, 80, 183, 185, 187, 199, 201, 202, 208, 214, 215, 231, 232 Neurologic, 13, 215, 234 Neurology, 6, 14, 25, 38, 40, 41, 91, 215 Neuromuscular, 215, 234 Neuronal, 215 Neurons, 198, 199, 215, 231 Neuropeptides, 13, 215 Neurotoxicity, 215, 236 Neutrons, 177, 215, 225 Nevirapine, 69, 215 Nicotine, 10, 215 Nitrates, 33, 215 Nitric acid, 215 Nitrogen, 17, 176, 177, 178, 215, 234 Non-nucleoside, 215 Norgestrel, 209, 215 Nuclear, 10, 11, 36, 191, 196, 198, 199, 211, 214, 215 Nucleic acid, 214, 215, 227 Nucleotidases, 204, 215 Nucleus, 181, 188, 193, 198, 199, 213, 215, 216, 223 Nursing Staff, 29, 216 O Observational study, 16, 216 Occult, 62, 216 Occupational Medicine, 19, 216 Ocular, 72, 216 Odour, 216, 234 Ointments, 195, 216 Oncology, 47, 69, 98, 103, 104, 143, 216 On-line, 9, 61, 173, 216 Opacity, 186, 193, 216 Optic Disk, 194, 210, 216 Oral Health, 3, 216 Orthopaedic, 90, 216 Osmotic, 176, 213, 216, 229 Osteoporosis, 12, 39, 108, 197, 216, 225 Outpatient, 8, 21, 24, 29, 30, 40, 49, 58, 78, 216 Overdosage, 57, 216 Overdose, 51, 55, 63, 216 Oxidation, 180, 181, 184, 193, 209, 216, 217 Oxidative Stress, 25, 217 P Palliative, 217, 232 Pancreas, 175, 194, 200, 217 Pancreatic, 200, 217 Pancreatic Juice, 200, 217 Pancreatitis, 5, 217
Parathion, 46, 217 Parenchyma, 14, 217 Parenteral, 84, 106, 217 Parenteral Nutrition, 84, 217 Particle, 133, 211, 212, 217 Patch, 6, 217 Pathogenesis, 24, 125, 129, 217 Pathologic, 118, 175, 181, 183, 192, 205, 217, 227 Pathologic Processes, 181, 217 Pathophysiology, 11, 136, 217 Patient Education, 164, 168, 170, 173, 217 Patient Satisfaction, 56, 218 Pediatrics, 46, 84, 218 Pelvic, 82, 90, 196, 218, 223 Penicillin, 177, 179, 218 Peptide, 12, 24, 32, 33, 189, 204, 218, 221, 223, 233 Peptide Chain Elongation, 189, 218 Peptide Hydrolases, 204, 218 Percutaneous, 65, 218 Perforation, 199, 218 Perfusion, 30, 218 Perineal, 164, 218 Perineum, 164, 218 Perioperative, 80, 218 Peritoneal, 56, 218 Peritoneal Cavity, 218 Peritoneal Dialysis, 56, 218 Peritoneum, 218 Petechiae, 202, 218 Pharmaceutical Solutions, 195, 218 Pharmacodynamic, 70, 218 Pharmacogenetics, 26, 27, 218 Pharmacokinetic, 19, 55, 64, 70, 89, 102, 130, 219 Pharmacologic, 129, 178, 182, 219, 233 Pharmacology, Clinical, 28, 219 Pharynx, 200, 219 Phenotype, 32, 52, 219 Phenprocoumon, 98, 219 Phenyl, 124, 219 Phenylalanine, 219, 234 Phospholipids, 150, 179, 180, 198, 209, 219 Phosphoric Monoester Hydrolases, 204, 219 Phosphorus, 124, 185, 219 Phosphorylated, 189, 219 Photocoagulation, 189, 219 Physical Examination, 187, 219 Physiologic, 136, 176, 183, 199, 219, 226, 227
248
Warfarin
Physiology, 28, 39, 200, 203, 214, 219, 227, 236 Pigmentation, 219, 236 Pilot study, 27, 34, 219 Pituitary Gland, 192, 219 Plants, 137, 176, 194, 200, 201, 213, 219, 220, 228, 233 Plants, Toxic, 137, 220 Plaque, 125, 178, 182, 220 Plasma cells, 179, 220 Plasma protein, 100, 126, 176, 197, 220, 223, 229 Plasmid, 198, 220 Plasmin, 13, 220 Plasminogen, 13, 136, 220 Plasminogen Activators, 220 Platelet Activation, 11, 44, 97, 220 Platelet Aggregation, 25, 38, 125, 178, 220, 233 Platelets, 11, 32, 125, 128, 181, 184, 214, 220, 232, 233 Platinum, 210, 220 Podophyllotoxin, 198, 220 Poisoning, 72, 79, 98, 187, 200, 207, 214, 220 Pollen, 220, 224 Polyethylene, 128, 221 Polyethylene Glycols, 128, 221 Polymers, 8, 128, 221, 223 Polymorphic, 11, 221 Polymorphism, 14, 28, 46, 52, 60, 61, 221 Polypeptide, 177, 189, 199, 220, 221, 237 Polysaccharide, 176, 180, 187, 201, 221 Polytherapy, 16, 221 Postmenopausal, 197, 216, 221, 225 Postoperative, 58, 74, 221 Post-translational, 32, 36, 37, 126, 221 Potassium, 138, 204, 213, 221, 224 Potentiate, 42, 221 Potentiation, 48, 61, 98, 103, 221 Practice Guidelines, 18, 160, 221 Precursor, 126, 181, 195, 197, 219, 220, 221, 223, 234, 236 Predisposition, 136, 222 Prednisolone, 222 Prednisone, 99, 222 Prenatal, 196, 222 Prevalence, 12, 14, 18, 72, 222 Primary endpoint, 38, 222 Primary Prevention, 35, 222 Probe, 16, 57, 98, 222 Progesterone, 209, 215, 222
Progression, 179, 222 Progressive, 33, 188, 197, 202, 213, 214, 220, 222, 226 Proline, 189, 204, 222 Prone, 13, 222 Prophylaxis, 13, 28, 30, 31, 49, 50, 54, 68, 69, 70, 75, 76, 77, 83, 88, 89, 90, 141, 222, 237 Propofol, 106, 222 Propranolol, 181, 222 Prospective Studies, 36, 222 Prospective study, 13, 59, 222 Prostaglandins, 181, 206, 223 Prostaglandins A, 206, 223 Prostate, 62, 108, 119, 146, 223 Prosthesis, 61, 223 Protease, 190, 223 Protein C, 33, 136, 153, 176, 177, 180, 182, 209, 223, 235 Protein S, 12, 22, 24, 136, 142, 183, 189, 197, 223, 227, 232 Proteolytic, 126, 190, 199, 220, 223 Prothrombin, 32, 36, 51, 53, 55, 73, 82, 126, 129, 136, 223, 232 Prothrombin Time, 82, 126, 129, 223 Protocol, 31, 42, 44, 47, 76, 223 Protons, 177, 204, 207, 223, 225 Protozoa, 191, 212, 223 Proximal, 31, 195, 223, 229 Pruritus, 223, 234 Psychiatric, 71, 211, 224 Psychiatry, 224, 236 Psychic, 224, 229 Psychology, 19, 194, 224 Psyllium, 113, 224 Public Health, 8, 160, 224 Public Policy, 159, 224 Publishing, 41, 224 Pulmonary, 28, 30, 35, 143, 164, 184, 188, 191, 202, 208, 224, 231, 236, 237 Pulmonary Artery, 184, 224, 236 Pulmonary Edema, 188, 224 Pulmonary Embolism, 35, 164, 224, 237 Pulsation, 199, 224 Pulse, 213, 224 Purpura, 202, 224 Purulent, 175, 196, 224 Putrefaction, 199, 224 Q Quality of Life, 5, 17, 224 Quercetin, 93, 224 Quinidine, 62, 188, 224
Index 249
Quinine, 137, 188, 224 Quinones, 137, 225 R Race, 8, 15, 39, 209, 215, 225 Radiation, 103, 104, 143, 178, 198, 199, 206, 207, 210, 211, 212, 225, 228, 237 Radiation therapy, 103, 104, 143, 198, 207, 225 Radioactive, 36, 184, 204, 206, 207, 209, 211, 213, 215, 225, 228 Radiolabeled, 225 Radiological, 218, 225 Radiotherapy, 184, 225 Radius, 10, 225 Raloxifene, 54, 225, 229 Random Allocation, 225 Randomization, 20, 225 Randomized clinical trial, 34, 118, 225 Reabsorption, 204, 226 Reagent, 188, 207, 226 Receptor, 11, 15, 32, 37, 180, 225, 226, 229 Recombinant, 33, 36, 51, 68, 74, 75, 80, 226 Recombinant Proteins, 36, 226 Rectum, 180, 184, 189, 194, 199, 200, 203, 206, 208, 223, 226 Recurrence, 14, 28, 31, 38, 39, 129, 164, 226 Reductase, 18, 36, 77, 226 Refer, 1, 185, 190, 199, 209, 210, 215, 226 Reflux, 149, 200, 226 Regeneration, 135, 226 Regimen, 3, 19, 28, 29, 30, 31, 56, 195, 226 Regurgitation, 200, 202, 203, 226 Relative risk, 175, 226 Reminder Systems, 18, 226 Remission, 226 Renal failure, 19, 226, 234 Renin, 186, 226 Renin-Angiotensin System, 186, 226 Reperfusion, 125, 227 Reperfusion Injury, 227 Resolving, 57, 227 Resorption, 37, 184, 226, 227 Respiration, 213, 227 Respiratory Physiology, 227, 236 Retina, 194, 208, 210, 227, 236 Retinal, 194, 216, 227, 236 Retinopathy, 68, 194, 219, 227 Reversion, 186, 227 Rheumatism, 205, 227 Ribavirin, 62, 227 Ribosome, 227, 234 Rickets, 228, 236
Rigidity, 219, 228 Risk factor, 8, 12, 15, 22, 24, 34, 35, 222, 226, 228 Risk patient, 31, 57, 228 Rodent Control, 125, 228 Rodenticides, 124, 125, 127, 131, 132, 138, 228 Rutin, 224, 228 S Salicylate, 106, 212, 228 Salicylic, 129, 228 Salivary, 194, 228 Salivary glands, 194, 228 Saphenous, 192, 228 Saphenous Vein, 192, 228 Scans, 30, 228 Schematic, 128, 228 Schizoid, 228, 237 Schizophrenia, 228, 237 Schizotypal Personality Disorder, 228, 237 Screening, 9, 23, 25, 189, 228, 235 Secretion, 33, 125, 192, 204, 205, 213, 228, 229 Sediment, 229, 235 Seizures, 143, 179, 229 Selective estrogen receptor modulator, 225, 229 Semen, 223, 229 Semisynthetic, 177, 189, 198, 229 Senile, 216, 229 Sepsis, 13, 229 Septal, 6, 229 Sequencing, 22, 24, 229 Sequester, 187, 229 Serous, 196, 229 Serum Albumin, 51, 52, 53, 55, 73, 78, 90, 229 Ships, 137, 229 Shock, 178, 229, 234 Shyness, 134, 229 Side effect, 129, 135, 151, 153, 164, 176, 214, 229, 233, 236 Signs and Symptoms, 226, 229, 234 Skeletal, 12, 39, 178, 213, 224, 229 Skeleton, 208, 229 Skull, 192, 229, 232 Small intestine, 188, 195, 200, 204, 207, 230 Smooth muscle, 33, 178, 182, 185, 204, 227, 230, 231 Social Environment, 224, 230 Social Support, 19, 230
250
Warfarin
Solvent, 124, 130, 131, 137, 138, 175, 183, 188, 201, 212, 216, 218, 230 Somatic, 175, 196, 213, 230 Specialist, 165, 230 Species, 42, 77, 137, 195, 197, 200, 213, 224, 225, 230, 231, 234, 236, 237 Specificity, 17, 31, 38, 176, 181, 230, 231 Sperm, 178, 188, 220, 230 Spinal cord, 43, 88, 184, 187, 188, 197, 211, 214, 230 Spirochete, 230, 232 Squamous, 230, 236 Staging, 228, 230 Standard therapy, 31, 33, 230 Steady state, 11, 55, 230 Steroids, 192, 201, 230 Stimulant, 185, 204, 230 Stomach, 131, 149, 175, 182, 194, 197, 200, 204, 210, 214, 218, 219, 226, 230 Stress, 19, 25, 56, 192, 200, 214, 217, 222, 231, 235 Stroma, 217, 231 Subacute, 206, 231 Subarachnoid, 202, 231 Subclinical, 206, 229, 231 Subcutaneous, 58, 70, 195, 217, 231 Subspecies, 230, 231 Substance P, 197, 212, 229, 231 Substrate, 10, 12, 16, 22, 33, 126, 197, 204, 231 Substrate Specificity, 17, 231 Sudden death, 27, 129, 231 Supplementation, 13, 97, 231 Suppression, 192, 231 Surfactant, 8, 231 Symphysis, 223, 231 Symptomatic, 31, 38, 40, 53, 119, 217, 231 Synaptic, 215, 231 Synaptic Transmission, 215, 231 Synergistic, 10, 102, 231 Syphilis, 149, 232 Systemic, 7, 11, 40, 152, 178, 179, 180, 184, 185, 197, 206, 222, 225, 232, 235, 237 Systemic lupus erythematosus, 179, 180, 232 Systolic, 205, 232 T Temporal, 37, 202, 210, 232 Teratogen, 37, 232 Testosterone, 226, 232 Tetracycline, 195, 232 Tetrahydronaphthalenes, 124, 232
Thalidomide, 8, 232 Theophylline, 48, 149, 165, 232 Therapeutics, 19, 45, 62, 63, 71, 75, 76, 101, 102, 119, 152, 232 Thermal, 130, 137, 194, 215, 232 Threshold, 198, 205, 232 Thrombin, 11, 13, 82, 126, 128, 136, 199, 220, 223, 232 Thrombocytes, 220, 232 Thrombocytopenia, 60, 82, 232 Thrombolytic, 13, 220, 232 Thrombomodulin, 223, 232 Thrombopenia, 180, 233 Thrombophlebitis, 164, 233 Thromboplastin, 223, 233 Thrombosed, 44, 233 Thromboses, 78, 180, 233 Thromboxanes, 181, 233 Thrombus, 4, 30, 55, 64, 135, 192, 206, 207, 214, 220, 232, 233, 235 Thyroid, 205, 233, 234 Thyroid Gland, 233 Thyrotropin, 205, 233 Thyroxine, 9, 176, 219, 233 Ticlopidine, 25, 113, 125, 233 Tissue, 4, 11, 13, 24, 37, 117, 135, 175, 180, 181, 183, 184, 186, 188, 189, 191, 194, 195, 196, 197, 198, 199, 202, 203, 205, 207, 208, 209, 210, 211, 214, 215, 217, 218, 219, 220, 223, 225, 226, 227, 229, 230, 231, 232, 233, 234 Topical, 42, 63, 181, 233 Torsion, 206, 233 Toxic, iv, 125, 137, 183, 188, 191, 194, 211, 214, 215, 217, 220, 233 Toxicity, 26, 85, 133, 134, 142, 195, 233 Toxicology, 46, 77, 82, 89, 105, 160, 233 Toxins, 180, 201, 206, 213, 233 Tramadol, 130, 234 Transcriptase, 215, 234 Transfection, 183, 234 Transient Ischemic Attacks, 109, 129, 234 Translation, 37, 197, 234 Translational, 13, 27, 32, 36, 37, 126, 221, 234 Translocation, 189, 197, 234 Transplantation, 33, 44, 188, 202, 205, 234 Trauma, 13, 27, 51, 72, 192, 202, 214, 217, 234 Trichomoniasis, 212, 234 Tryptophan, 189, 234 Tuberculosis, 191, 210, 228, 234
Index 251
Tumor Necrosis Factor, 232, 234 Tunica Intima, 196, 234 Tyrosine, 37, 234 U Ubiquitin, 38, 234 Ulcer, 11, 208, 234, 235 Ulceration, 129, 208, 234 Unconscious, 205, 234 Uraemia, 102, 217, 234 Urea, 182, 234, 235 Uremia, 226, 235 Urethra, 223, 235 Uric, 183, 201, 235 Urinalysis, 25, 235 Urinary, 82, 90, 182, 189, 235 Urine, 15, 124, 182, 184, 192, 194, 195, 235 Urokinase, 44, 235 Urticaria, 178, 235 Uvea, 196, 235 V Vaccine, 223, 235 Vagina, 185, 235 Vaginal, 42, 147, 235 Valves, 18, 46, 59, 76, 202, 235 Varicose, 109, 208, 235 Vascular, 4, 6, 15, 40, 58, 71, 119, 177, 178, 187, 196, 197, 202, 206, 210, 220, 233, 235 Vascular Resistance, 177, 235 Vasculitis, 217, 235 Vasoactive, 14, 235 Vasodilator, 184, 204, 235 Vasomotor, 197, 235 Vein, 30, 50, 65, 68, 75, 83, 88, 89, 105, 142, 181, 192, 207, 215, 228, 233, 235 Venereal, 232, 235 Venous Thrombosis, 7, 28, 30, 31, 35, 40, 83, 233, 235, 237
Ventilation, 30, 236 Ventricle, 180, 224, 232, 236 Ventricular, 27, 33, 119, 177, 195, 236 Ventricular Dysfunction, 195, 236 Ventricular fibrillation, 27, 33, 236 Venules, 184, 186, 197, 236 Verapamil, 130, 236 Vertebrae, 230, 236 Vesicular, 212, 236 Veterinary Medicine, 159, 236 Vindesine, 106, 236 Viral, 5, 25, 236 Virulence, 233, 236 Virus, 5, 182, 187, 220, 236 Vitamin D, 13, 92, 228, 236 Vitamin K, 12, 36, 37, 43, 83, 92, 93, 112, 113, 147, 236 Vitreoretinal, 79, 236 Vitreous Hemorrhage, 194, 236 Vitro, 11, 13, 16, 22, 32, 33, 37, 62, 73, 77, 203, 206, 236 Vivo, 11, 15, 22, 24, 32, 33, 37, 203, 206, 233, 237 W Watchful waiting, 84, 237 White blood cell, 179, 208, 210, 214, 220, 237 Withdrawal, 7, 40, 237 X Xenograft, 179, 237 X-ray, 39, 190, 199, 210, 211, 215, 225, 228, 237 Y Yeasts, 199, 219, 237 Z Zymogen, 223, 237
252
Warfarin
