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

DIGOXIN 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., 1960Digoxin: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-497-00365-1 1. Digoxin-Popular works. I. Title.

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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.

Copyright Notice If a physician wishes to copy limited passages from this book for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications have copyrights. With exception to the above, copying our publications in whole or in part, for whatever reason, is a violation of copyright laws and can lead to penalties and fines. Should you want to copy tables, graphs, or other materials, please contact us to request permission (E-mail: [email protected]). ICON Group often grants permission for very limited reproduction of our publications for internal use, press releases, and academic research. Such reproduction requires confirmed permission from ICON Group International, Inc. The disclaimer above must accompany all reproductions, in whole or in part, of this book.

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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on digoxin. 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 DIGOXIN.................................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Digoxin ......................................................................................... 4 E-Journals: PubMed Central ....................................................................................................... 17 The National Library of Medicine: PubMed ................................................................................ 20 CHAPTER 2. NUTRITION AND DIGOXIN .......................................................................................... 63 Overview...................................................................................................................................... 63 Finding Nutrition Studies on Digoxin ........................................................................................ 63 Federal Resources on Nutrition ................................................................................................... 66 Additional Web Resources ........................................................................................................... 66 CHAPTER 3. ALTERNATIVE MEDICINE AND DIGOXIN.................................................................... 69 Overview...................................................................................................................................... 69 National Center for Complementary and Alternative Medicine.................................................. 69 Additional Web Resources ........................................................................................................... 82 General References ....................................................................................................................... 87 CHAPTER 4. DISSERTATIONS ON DIGOXIN ..................................................................................... 89 Overview...................................................................................................................................... 89 Dissertations on Digoxin ............................................................................................................. 89 Keeping Current .......................................................................................................................... 90 CHAPTER 5. PATENTS ON DIGOXIN ................................................................................................ 91 Overview...................................................................................................................................... 91 Patents on Digoxin ...................................................................................................................... 91 Patent Applications on Digoxin ................................................................................................ 110 Keeping Current ........................................................................................................................ 115 CHAPTER 6. BOOKS ON DIGOXIN .................................................................................................. 117 Overview.................................................................................................................................... 117 The National Library of Medicine Book Index ........................................................................... 117 Chapters on Digoxin .................................................................................................................. 118 CHAPTER 7. PERIODICALS AND NEWS ON DIGOXIN .................................................................... 119 Overview.................................................................................................................................... 119 News Services and Press Releases.............................................................................................. 119 Academic Periodicals covering Digoxin .................................................................................... 121 CHAPTER 8. RESEARCHING MEDICATIONS .................................................................................. 123 Overview.................................................................................................................................... 123 U.S. Pharmacopeia..................................................................................................................... 123 Commercial Databases ............................................................................................................... 124 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 127 Overview.................................................................................................................................... 127 NIH Guidelines.......................................................................................................................... 127 NIH Databases........................................................................................................................... 129 Other Commercial Databases..................................................................................................... 131 APPENDIX B. PATIENT RESOURCES ............................................................................................... 133 Overview.................................................................................................................................... 133 Patient Guideline Sources.......................................................................................................... 133 Finding Associations.................................................................................................................. 135 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 137 Overview.................................................................................................................................... 137 Preparation................................................................................................................................. 137 Finding a Local Medical Library................................................................................................ 137

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Medical Libraries in the U.S. and Canada ................................................................................. 137 ONLINE GLOSSARIES................................................................................................................ 143 Online Dictionary Directories ................................................................................................... 144 DIGOXIN DICTIONARY ............................................................................................................ 145 INDEX .............................................................................................................................................. 203

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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 digoxin 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 digoxin, 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 digoxin, 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 digoxin. 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 digoxin, 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 digoxin. 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 DIGOXIN Overview In this chapter, we will show you how to locate peer-reviewed references and studies on digoxin.

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

Drug/Nutrient Interactions Involving Twenty of the Most Commonly Prescribed Medications in the United States Source: Journal of Practical Hygiene. 9(1): 39-48. January-February 2000. Contact: Available from Montage Media Corporation. 1000 Wyckoff Avenue, Mahwah, NJ 07430-3164. (201) 891-3200. Summary: The increased use of prescribed medication in the United States has established the need for dental professionals to understand the possible interactions between medications and nutrients. This article discusses interactions between nutrients and the 20 most commonly prescribed medications in 1998: conjugated estrogen, levothyroxine, amoxicillin, hydrocodone, fluoxetine, omeprazole, azithromycin, atorvastin, amlodipine, loratine, digoxin, sertaline, aerosol, paroxetine, amoxicillin,

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lisinopril, enalapril, amoxicillin clavulanate potassium, and cephalexin. In addition, a discussion of practical considerations for the dental hygiene practice is provided. The authors stress that thoroughly completing and reviewing the dental patient's medical and drug history, as well as conducting a diet assessment, are methods by which the dental hygienist can determine if a patient's health is at risk due to drug and nutrient interactions. 3 figures. 2 tables. 38 references.

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

Project Title: ACTION - A CHF TRIAL INVESTIGATING OUTCOMES OF EXERCISE Principal Investigator & Institution: Bittner, Vera A.; Professor of Medicine; Medicine; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-JUL-2006 Summary: (provided by applicant): The primary aim of the ACTION Trial is to determine the long-term safety and effectiveness of exercise training for New York Heart Association Classes II-IV congestive heart failure patients in addition to standard of care versus a strategy of standard care alone. The secondary objective is to determine the incidence and significance of exercise-related complications, the effect on exercise tolerance and quality of life, and the cost-effectiveness of training. The exercise training will include 36 facility-based training sessions followed by home-based exercise and interval facility sessions. Training will be at 60-70% of heart rate reserve. Patients randomized to the training arm will train by either walking or bicycle ergometers. Treadmills or exercise bicycles will be provided to training patients by the coordinating center, if desired. Effectiveness will be defined as the primary combined endpoint of allcause mortality and all-cause hospitalizations. The expected annual baseline rate is 30% for the control group. The expected non-adherence and drop-out rate is 35% the first year and 15% annually thereafter, with a cross-over rate of 5% per year. The regional center team and the coordinating center will implement multiple strategies to improve adherence in patients in the training arm. Using these assumptions, a total sample size

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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of 3000 subjects will be required to detect a 20% reduction in the primary outcome with an alpha level of 0.05 and a power greater than 80%. If the non-adherence and drop-out rate decrease to 30% in the first year and 12.5% annually thereafter, the power to detect a 20% difference is greater than 90%. The primary analysis will be based on intent-to-treat. The trial will take place over 5 years with an initial 6 months for planning, training, and implementation; 3 years of enrollment; 1 year of follow-up; and 6 months for close out, analysis, and presentation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ACTION EQOL STUDY Principal Investigator & Institution: Schulman, Kevin A.; Professor of Medicine and Director,; Medicine; Duke University Durham, Nc 27710 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-JUL-2007 Summary: (provided by applicant): The primary aim of the ACTION Trial is to determine the long-term safety and effectiveness of exercise training for New York Heart Association Classes II-IV congestive heart failure patients in addition to standard of care versus a strategy of standard care alone. The secondary objective is to determine the incidence and significance of exercise-related complications, the effect on exercise tolerance and quality of life, and the cost-effectiveness of training. The exercise training will include 36 facility-based training sessions followed by home-based exercise and interval facility sessions. Training will be at 60-70% of heart rate reserve. Patients randomized to the training arm will train by either walking or bicycle ergometers. Treadmills or exercise bicycles will be provided to training patients by the coordinating center, if desired. Effectiveness will be defined as the primary combined endpoint of allcause mortality and all-cause hospitalizations. The expected annual baseline rate is 30% for the control group. The expected non-adherence and drop-out rate is 35% the first year and 15% annually thereafter, with a cross-over rate of 5% per year. The regional center team and the coordinating center will implement multiple strategies to improve adherence in patients in the training arm. Using these assumptions, a total sample size of 3000 subjects will be required to detect a 20% reduction in the primary outcome with an alpha level of 0.05 and a power greater than 80%. If the non-adherence and drop-out rate decrease to 30% in the first year and 12.5% annually thereafter, the power to detect a 20% difference is greater than 90%. The primary analysis will be based on intent-to-treat. The trial will take place over 5 years with an initial 6 months for planning, training, and implementation; 3 years of enrollment; 1 year of follow-up; and 6 months for close out, analysis, and presentation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ACTION-A CHF TRIAL INVESTIGATING OUTCOMES OF EXERCISE Principal Investigator & Institution: Abraham, William T.; Professor of Medicine; Internal Medicine; Ohio State University 1960 Kenny Road Columbus, Oh 43210 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-JUL-2006 Summary: (provided by applicant): The primary aim of the ACTION Trial is to determine the long-term safety and effectiveness of exercise training for New York Heart Association Classes II-IV congestive heart failure patients in addition to standard of care versus a strategy of standard care alone. The secondary objective is to determine the incidence and significance of exercise-related complications, the effect on exercise tolerance and quality of life, and the cost-effectiveness of training. The exercise training will include 36 facility-based training sessions followed by home-based exercise and

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interval facility sessions. Training will be at 60-70% of heart rate reserve. Patients randomized to the training arm will train by either walking or bicycle ergometers. Treadmills or exercise bicycles will be provided to training patients by the coordinating center, if desired. Effectiveness will be defined as the primary combined endpoint of allcause mortality and all-cause hospitalizations. The expected annual baseline rate is 30% for the control group. The expected non-adherence and drop-out rate is 35% the first year and 15% annually thereafter, with a cross-over rate of 5% per year. The regional center team and the coordinating center will implement multiple strategies to improve adherence in patients in the training arm. Using these assumptions, a total sample size of 3000 subjects will be required to detect a 20% reduction in the primary outcome with an alpha level of 0.05 and a power greater than 80%. If the non-adherence and drop-out rate decrease to 30% in the first year and 12.5% annually thereafter, the power to detect a 20% difference is greater than 90%. The primary analysis will be based on intent-to-treat. The trial will take place over 5 years with an initial 6 months for planning, training, and implementation; 3 years of enrollment; 1 year of follow-up; and 6 months for close out, analysis, and presentation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ATRIAL FIBRILLATION FOLLOW UP OF RHYTHM MANAGEMENT (AFFIRM) Principal Investigator & Institution: Pritchett, Edward L.; Duke University Durham, Nc 27710 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CARDIAC AMYLOIDOSIS IN AGING AFRICAN AMERICANS Principal Investigator & Institution: Buxbaum, Joel N.; Professor; Scripps Research Institute Tpc7 La Jolla, Ca 92037 Timing: Fiscal Year 2002; Project Start 01-JUL-2001; Project End 30-JUN-2006 Summary: (Verbatim from the application): If factors related to access to care are not considered, the increased mortality from cardiovascular disease in African-Americans relative to other groups is due to the increased frequency of some diseases, a qualitatively different cardiac response to disorders affecting all ethnic groups and a relatively poor response to treatment of congestive heart failure. An undiagnosed, coexistent, relatively prevalent, treatment-resistant cardiomyopathy is a possible partial explanation. Late onset amyloidotic cardiomyopathy is fourfold more common in African-Americans than Caucasians. It causes congestive heart failure and arrhythmias, however these features are relatively non-specific and the clinical diagnosis is not always obvious. Digoxin and calcium channel blockers are toxic in patients with amyloid, thus, treatment of concomitant heart disease of other etiologies may be compromised; moreover misdiagnosis of amyloid heart disease may result in possibly harmful therapy. Unrecognized amyloidosis, in individuals over age 60, could contribute to some of the refractoriness seen in studies of congestive heart failure and to the higher cardiovascular morbidity and mortality in African-Americans. Our proposal examines a genetically determined form of late-onset amyloidosis due to a substitution of ILE for VAL at position 122 in the serum protein transthyretin (TTR). Approximately 4% of African-Americans are heterozygous for the allele that has an absolute risk for anatomic amyloid deposition after age 60 resulting in 154,000 African-Americans with

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some degree of cardiac amyloidosis. In a collaborative effort with two studies of cardiovascular risk in the community (ARIC and CFIS), with a combined AfricanAmerican cohort of 5200, we will test the hypothesis that heterozygosity for the amyloidogenic allele is associated with clinical evidence of cardiac amyloidosis and a related increase in mortality. We will also assess the role of the allele in clinical heart disease by determining its prevalence in a cohort of African-American veterans, over 60, who are recognized as having heart disease, although their providers have not considered amyloidosis as a specific diagnosis. We will characterize the natural history of late onset cardiac amyloidosis in African-Americans, define its role in cardiovascular morbidity and mortality in this ethnic group and define guidelines for supportive treatment at present and specific therapy when available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TRAINING

CHF

TRIAL

INVESTIGATING

OUTCOMES

OF

EXERCISE

Principal Investigator & Institution: Kitzman, Dalane W.; Professor; Internal Medicine; Wake Forest University Health Sciences Winston-Salem, Nc 27157 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-JUL-2006 Summary: (Applicant?s Abstract) The primary aim of ACTION is to determine the longterm safety and efficacy of exercise training for New York Heart Association Classes IIIV congestive heart failure patients in addition to standard of care versus a strategy of standard care alone. The secondary objective is to determine the incidence and significance of exercise-related complications. As part of this objective, the investigators will determine the specific characteristics of patients with increased benefit or increased risk from exercise. The exercise training will include 36 supervised training sessions followed by home exercise and interval supervised sessions. Training will be at 60-70% of peak VO2. Efficacy will be defined as the primary combined endpoint of all-cause mortality and all-cause hospitalizations. These clinical endpoints will be supported by physiological, resource utilization, and quality-of-life endpoints. The expected annual baseline rate is 30% for the control group. The expected dropout rate is 35% for the first year and 15%, with a cross-over rate of 5% per year. Using these assumptions, a total sample size of 3000 subjects will be required to detect a 20% reduction in the primary outcome with an alpha level of 0.05 and a power of 80%. The trial will take place over 5 years with an initial 6 months for finalizing the study and training the Regional Centers, 3 years of enrollment, 1 year of follow-up, and 6 months for close out, analysis and presentation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EFFECTS OF ITRACONAZOLE & KETOCONAZOLE ON DIGOXIN PHARMACOKINETICS Principal Investigator & Institution: Benet, Leslie; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: FUNCTIONS OF THE HEPATIC GAMMA-GLUTAMYL CYCLE Principal Investigator & Institution: Ballatori, Nazzareno A.; Associate Professor of Environmental Med; Environmental Medicine; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2002; Project Start 01-SEP-1995; Project End 31-AUG-2003 Summary: (Adapted from investigator's abstract) Reduced glutathione (GSH) plays a critical role in a multitude of biochemical processes, and disturbances in its homeostasis are implicated in the etiology and progression of a number of diseases. The initial step in the turnover of this tri-peptide in all mammalian cells is its transport into the extracellular space; however, the transport systems that mediate GSH efflux remain poorly defined. In the liver, a major site of GSH synthesis, GSH is released at high rates into both blood plasma and bile. GSH transport into bile functions as a driving force for bile secretion and plays an important role in hepatic detoxification of drugs, metals, and other reactive compounds of both endogenous and exogenous origin. GSH is also released across the sinusoidal membrane into blood plasma for delivery to other tissues. Our recent studies provide important insight into molecular mechanisms of GSH transport. In particular, we demonstrated that oatp1, the sinusoidal organic solute transporter, functions as a GSH/organic solute exchanger. This finding not only identifies the energy coupling mechanism for oatp1, but also elucidates a pathway for GSH release into blood plasma, as well as a novel function for GSH. Moreover, we demonstrated that Ycf1p, the yeast orthologue of mammalian mrp proteins, mediates ATP-dependent, low-affinity GSH transport, indicating that mrp may mediate GSH efflux in mammalian cells. The overall goals of the proposed studies are to identify and characterize GSH and glutathione S-conjugate transport mechanisms, and in particular to test the hypothesis that the oatp- and mrp-family of transporters mediate cellular GSH release. Our specific aims are: (1) Test whether oatp2, a recently cloned transporter that is homologous to oatp1, also mediates GSH/organic solute exchange. (2) Establish the kinetics and specificity of GSH transport on oatp1, and on oatp2 if this transporter is also found to function as a GSH exchanger. (3) Test whether GSH is a substrate or a cosubstrate for mrp2, and if so; a) define the energetics of transport on this canalicular membrane protein, b) compare these parameters with those for GSH transport on yeast Ycf1p, and c) examine whether GSH is also a substrate for mrp3 and mrp6, putative hepatocellular lateral membrane proteins; and (4) Continue to define the role of the intrahepatic -glutamyl cycle in the disposition of glutathione S-conjugates and their conversion to the corresponding mercapturic acids by examining mechanisms of mercapturic acid transport. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HEPATIC/INTESTINAL P-GLYCOPROTEIN PREGNANCY

AND

CYP3A

IN

Principal Investigator & Institution: Unadkat, Jashvant D.; Professor; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2007 Summary: Pregnant women and their fetuses are therapeutic "orphans." Drugs are administered to pregnant women, and therefore their fetuses, without the necessary clinical data about the pharmacokinetics, dose, safety, or efficacy of the drugs in these vulnerable populations. To determine the correct dose of a drug to administer to the pregnant woman, it is important to know if the pharmacokinetics of the drug are different in pregnant women when compared with men or non-pregnant women. Many

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drugs administered to pregnant women are substrates of P-glycoprotein (P-gp) or cytochrome P450 3A enzymes (CYPCA4/5) or both, such as antivirals (e.g., anti-HIV protease inhibitors, antibiotics (e.g., clarithromycin), antihistamines (e.g., fexofenadine), and anti-epileptics (e.g, carbamazepine). P-gp and CYP3A4/5 enzymes are strategically located in the intestine, liver and kidneys?organs important for absorption, metabolism, and excretion of drugs. We have recently obtained evidence from perinatal Phase I clinical trial on indinavir, an anti-HIV protease inhibitor, that the oral clearance of this drug is increased approximately 3-fold during pregnancy. Since the disposition of indinavir is determined by P-gp and CYP3A4/5 enzymes in the intestine and liver, we hypothesized that P-gp and CYP3A4/5 expression and activity in these tissues are enhanced during pregnancy. The Specific Aims listed below are designed to test this hypothesis. Hypothesis Hepatic and Intestinal P-glycoprotein and CYP3A4/5 expression and activity is enhanced during pregnancy Specific Aims 1. To determine, both antenatal and postpartum, in vivo intestinal and hepatic P-glycoprotein and CYP3A4/5 activities in pregnant women by oral administration of selective substrates of P-gp (digoxin) and CYP3A4/5 (midazolam). 2. To determine, in vivo (or ex vivo), both antenatal and postpartum, intestinal and hepatic P-glycoprotein and CYP3A4/5 activities (or expression) following oral and IV administration of protease inhibitors to a representative animal model, the pregnant M. nemestrina. 3. To determine if activity and expression of P-gp in lymphocytes is elevated during pregnancy in women and M. nemestrina. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HERB-OPIOID INTERACTIONS Principal Investigator & Institution: Shen, Danny D.; Member; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2002; Project Start 10-SEP-2001; Project End 31-MAY-2004 Summary: (provided by applicant):Extract of SJW; Hypericum perforatum, has gained widespread popularity as an over-the-counter, natural antidepressant. Until recently, SJW was thought to be well tolerated and relatively safe. Within the past year, adverse metabolic interactions have been reported between SJW and several narrow therapeutic index drugs, notably cyclosporine indinavir, and digoxin. The interactions are now recognized to involve induction of two drug disposition mechanisms: cytochrome P450 3A4 enzyme and the active efflux pump, P-glycoprotein, both leading to profound reductions in blood or plasma drug concentration that compromises the therapeutic efficacy of the affected drug. Natural and synthetic opioids are the first-line agents for the palliative treatment of severe pain that results from cancer and cancer treatment. It is well recognized that depression is a co-morbid condition of severe and poorly controlled cancer-related pain. Given the widespread recognition of St. Johns wort as a "mood enhancer" and natural antidepressant, cancer pain patients receiving opioid analgesics may well turn to this herbal preparation for relief of depressive symptoms. The overall objective of this research proposal is to investigate if significant interactions occur between two widely used opioid analgesics - oxycodone and fentanyl and St. John wort extract through laboratory-based studies in healthy volunteers. The studies will assess the potential clinical significance of the interactions with respect to opioid analgesia efficacy and side effects, and provide scientific insights into the pharmacokinetic mechanisms underlying any observed interactions. The oxycodone arm of the study is designed to 1) investigate the induction of CYP3A4-mediated Ndemethylation which is the major detoxification pathway for oxycodone, and 2) resolve the inductive effects of SJW on intestinal and hepatic CYP3A4 through intravenous and

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oral administrations of a CYP3A-specific, in vivo catalytic probe -midazolam. The fentanyl arm of the study will 1) assess the effects of SJW on the brain uptake and efflux kinetics of fentanyl through pharmacokinetic-pharmacodynamic (PK-PD) modeling of miotic response over time during and following intravenous infusion of the opioid, and 2) to evaluate the changes in analgesia and side effects of fentanyl upon pretreatment with SJW that may have resulted from induction of Pgp at the BBB. A third arm of the study will assess whether SJW has analgesic properties of its own, or is capable of promoting opioid analgesia. Overall, the proposed research will provide a definitive assessment of the potential and clinical significance of adverse interactions between SJW and opioids in the context of cancer pain therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IMPROVING PATIENT SAFETY BY REDUCING MEDICATION ERRORS Principal Investigator & Institution: Strom, Brian L.; Professor of Medicine and Pharmacology; Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 07-SEP-2001; Project End 31-AUG-2006 Summary: (PROVIDED BY APPLICANT) Medication errors are among the most common and potentially preventable types of medical errors, accounting for more deaths than motor vehicle accidents, breast cancer, or HIV, and an annual cost of $17 to 29 billion. The elderly are particularly at risk for such complications. The highest risk 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 dose-

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related medication errors among elderly individuals taking specific high-risk drugs (warfarin, phenytoin, and digoxin), using a State-run population-based pharmaceutical benefit program. Project 2 will study human and medical practice factors as predictors of poor adherence to warfarin therapy in an anticoagulation clinic setting created as a systems approach to prevent medication errors. Project 3 will study medication errors as causes of preventable acute renal failure in the inpatient setting, despite the existence of a pharmacokinetic monitoring service created to prevent such problems. Project 4 will study conditions that lead to medication errors among physicians, with emphasis on work conditions that increase stress, such as workload, schedules, work organization, shifts, and patient/staff ratios. Core A will be an administrative core, responsible for coordination. Core B will be a data collection core, responsible for all field activities. Core C will be a biostatistics and data management core, responsible for data entry, management, and analysis. Core D will be a dissemination core, responsible for an extensive dissemination program, as the results of the program emerge. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MEDICATION ERRORS LEADING TO HOSPITALIZATION OF THE AGED Principal Investigator & Institution: Metlay, Joshua P.; Assistant Professor of Medicine & Epidem; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2003 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

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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, 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: METABOLISM OF DIGITALIS LIKE FACTORS Principal Investigator & Institution: Valdes, Roland; Pathology and Lab Medicine; University of Louisville Jouett Hall, Belknap Campus Louisville, Ky 40292 Timing: Fiscal Year 2002; Project Start 15-DEC-1998; Project End 30-NOV-2004 Summary: The human adrenal synthesizes and secretes a variety of important regulatory hormones. The adrenal cortex secretes an endogenous digoxin- like immunoreactive factor (DLIF) into the circulation. The chemical composition of DLIF is remarkably similar to that of the cardioactive cardenolides. We have recently identified a precursor and several metabolic products of DLIF. However, the detailed structure of these compounds is not known. Several studies demonstrate elevated levels of endogenous DLIF in serum from patients with essential hypertension (EH), pregnancy induced hypertension (PIH), and during cardiac dysfunction. DLIF may control the iontransport activity of ouabain-sensitive sodium- potassium ATPase. Several isoforms of the Na,K-ATPase (sodium pump) have been identified in tissue. Na/K-ATPase is the only known receptor for the cardenolides and is an important modulator of vascular smooth muscle tone in arterioles as well as other cardiovascular events. Inhibition of the sodium pump causes vasoconstriction which leads to systemic hypertension. A combination of DLIF from the adrenal cortex (as hormone) and sodium pump isoforms (as receptors) may form a regulatory hormonal-axis and play an important role in the etiology of EH and PIH. We propose a working hypothesis: DLIF from human adrenal cortex are endogenous inhibitors of ouabain-sensitive sodium-potassium ATPase and by this mechanism affect blood pressure in mammals. The aim of this project is to define the chemical structure of DLIF and its biotransformation in tissue. Several chemicalidentification techniques will be used to determine the structure of DLIF and its metabolic congeners. Biotransformation will be studied using in vitro metabolic techniques. Four independent measures of digitalis-like activity (immunoreactivity; Na,K-ATPase receptor binding; Na,K-ATPase catalytic activity; and ion-transport activity) will be used to characterize the interaction of DLIF and its metabolic precursors and products with the sodium pump. This research will provide the much needed chemical structure of DLIF, define its structural changes during metabolism, and test the hypothesis that DLIF from adrenals are endogenous inhibitors of sodium-potassium ATPase. These factors may prove useful in elucidating the mechanism responsible for EH or PIH and provide much needed diagnostic markers for these and other cardiovascular diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MODULATION OF HUMAN MDR1 FUNCTION IN VIVO Principal Investigator & Institution: Wood, Alastair J J.; Professor; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917

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Timing: Fiscal Year 2002; Project Start 01-DEC-1982; Project End 30-JUN-2007 Summary: (provided by applicant): Membrane transporters are increasingly recognized to be important in drug disposition. For example, the efflux transporter MDR1 (Pglycoprotein) impairs oral absorption, limits distribution into certain tissues pharmacologic sanctuary sites - and enhances excretion via the liver, kidney and intestinal tract. Accordingly, modulation of MDR1 function by either inhibition or induction can, in principle, significantly alter a drug?s disposition and its pharmacological effect. However, supportive evidence for such changes in humans and, more importantly, their application to beneficially alter drug responsiveness is currently limited. In the case of MDR1 inhibition, the limitation has been the lack of an appropriate potent and selective drug for this purpose. This Project proposes to use a drug with these necessary characteristics as a tool to investigate the consequences and therapeutic potential of MDR1 inhibition in humans. Specific Aim 1 proposes to test the hypothesis that inhibition of MDR1 function affects target tissue availability and drug responsiveness, especially at a pharmacologic sanctuary site such as the brain. This will be accomplished by the use of a probe, wherein MDR1 inhibition would be expected to change it from a centrally ineffective drug into one with efficacy. By contrast, Specific Aim 2 focuses on the effect of MDR1 inhibition on systemic drug availability. Studies are proposed with digoxin and fexofenadine - two drugs that are essentially excreted unchanged and whose disposition appears to be MDR1-dependent. Accordingly, they may serve as in vivo probes for the transporter if such a role is validated. Because of the overlap between MDR1 substrates/inhibitors and those of cytochrome P4503A (CYP3A), studies are also proposed to investigate the selectivity of inhibition of the transporter using midazolam and the erythromycin breath test as in vivo probes of CYP3A. Additional studies will also define the relative contribution of MDR1 and CYP3A in the disposition of drugs like cyclosporine-A and erythromycin, which are substrates of both proteins. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NA/K PUMP CURRENT IN ISOLATED HEART CELLS Principal Investigator & Institution: Gadsby, David C.; Professor; Lab/Cardiac/Membrane Physiol; Rockefeller University New York, Ny 100216399 Timing: Fiscal Year 2002; Project Start 01-APR-1987; Project End 31-MAR-2006 Summary: (provided by applicant): The long term goal remains a detailed understanding of how the Na/K pump works and how it may be modulated. The Na/K pump plays the vital role of maintaining the electrochemical gradients for Na and K ions that underlie electrical signaling, essential coupled transport, and cell pH and volume regulation; the Na/K pump is also the receptor for the still widely prescribed cardiotonic steroid, and pump inhibitor, digoxin. Charge translocation is a fundamental feature of the ion pumping cycle, and of individual partial reactions. It provides a readily accessible, reproducible, and sensitive signal for assaying turnover rates and rates of conformational transitions, and sheds light on the molecular mechanism of ion transport, now viewed in light of the new high-resolution crystal structure of the related SR Ca pump. Specific aim (1) is to further investigate the ion transport mechanism, using two approaches. In one, we will continue characterizing the charge translocating steps by quantitative analysis of the dependence on membrane potential, external and internal ion and nucleotide concentrations, and temperature, of steady- and pre-steadystate pump currents in internally dialyzed guinea-pig ventricular myocytes and squid giant axons (in which technical advances now permit ultra high-speed measurements of pump-mediated charge movements, resolving relaxation rates as fast as 10 to the 5th

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power per s, some 3 orders of magnitude faster than the Na/K pump's maximum turnover rate. In the other, the lethal coral toxin, palytoxin, is used to transform the Na/K pump into a gated ion channel. We will express in HEK293 cells mutant ouabainresistant Na/K pumps with cysteine residues introduced at strategic locations, and then use sulfhydrl-specific reagents to investigate structure of the gates and mechanisms of gating, which should provide information on ion occlusion/deocclusion mechanisms during normal Na/K pumping. Specific aim (2) is to see whether, under what conditions, and by which mechanisms, Na/K pump activity in myocytes may be acutely modulated by cellular regulatory processes like kinase-mediated phosphorylation of the pump (or associated regulatory molecule), or interactions with cytoplasmic Ca ions. We will directly apply regulatory molecules, such as purified kinases or phosphatases, to the pump's cytoplasmic surface in giant inside-out patches of membrane, excised from myocytes. Explicit kinetic models of the Na/K transport mechanism will be developed to account for experimental observations, and will be refined by fits to the data. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: POLYMORPHISM OF MULTI-DRUG-RESISTANCE PROTEIN-1 Principal Investigator & Institution: Ho, Rodney J.; Professor; Pharmaceutics; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 10-JAN-2002; Project End 31-DEC-2005 Summary: (provided by applicant): The long-term goal of this program is to elucidate the genetic and functional correlates of drug transporters that influence inter-individual variations in drug disposition and therapeutic outcome. Variations in the 170 kd membrane bound, efflux transporter P-glycoprotein (P-gp, often referred to as multidrug resistance protein-1 or MDR-1) in adult subjects produce up to a 7-fold difference in bioavailability of digoxin, a P-gp substrate. P-gp is expressed in tissues central to in vivo drug disposition, including the liver, gut, blood-brain barrier, placenta, and kidney. While a number of genetic variants of MDR-1 have been demonstrated in continuous cell-lines, their frequency and clinical significance has not been fully established. A more robust and reliable RT-PCR method was developed recently to simultaneously quantitate MDR-1 mRNA and isolate 3.8 kb cDNA from total cellular RNA. As a result, an efficient cloning and expression of MDR-1 cDNA in an expression vector is now feasible. We will use these cDNA vectors to systematically evaluate functional variation of a large series of cDNA from leukemia patients. With this proposal, we will identify genetic variations that produce significant effects on the efflux function of Pgp with the following aims: Aim 1: to identify genetic variants of MDR- 1 from DNA and RNA isolated from leukemic (AML and MDS) patients. Aim 2: to determine functional significance of genetic variants identified from the leukemic patients By integrating the results of Aims 1 and 2, we can begin to define the role of genetic variations on the P-gp efflux function. The proposed studies will elucidate the role of MDR-1 genetic polymorphism in functional P-gp variations and may shed light on their modulation of systemic and CNS availability and disposition of drugs from a wide range of therapeutic classes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: POTASSIUM AND THE MUSCLE REFLEX IN HUMAN SUBJECTS Principal Investigator & Institution: Daley, Joseph C.; Medicine; Pennsylvania State Univ Hershey Med Ctr 500 University Drive Hershey, Pa 170332390 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2006

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Summary: PROPOSAL (Adapted from the applicant's abstract): The long-term goal of the principal investigator (PI) is to become a clinician scientist examining issues pertaining to autonomic regulation in health and disease. The main objective of this project is to examine the metabolic and mechanical factors that initiate and sustain the muscle exercise pressor reflex. This reflex is a major determinant of blood flow and pressure during exercise. In addition, diseases, such as congestive heart failure (CHF) are associated with pathologic activation of this reflex and may contribute to the morbidity and mortality of this common disorder. Two basic theoretical components of neural control of circulation predominate. "Central command," a feed forward signal emanating from the central motor areas, suggests that neural motor and sympathetic activation occur in parallel. This system may be integrally linked to skeletal muscle metabolic demand. The second component of the reflex is the muscle reflex, and is the subject of this investigation. It is clear chemical byproducts of muscle contraction can evoke a pressor response. However, the specific interstitial chemical(s) that stimulate the muscle fiber afferents, and engage the reflex, remains an area of considerable controversy. This study proposes investigation of the relationship between interstitial potassium concentration and muscle sympathetic nervous activity (MSNA). Recent studies have implicated potassium as a potential mediator of the muscle reflex; however, conclusive evidence linking interstitial K+ with MSNA does not exist. The investigators will examine the "real time" interstitial concentration of potassium in exercising muscle and MSNA simultaneously, as well as venous plasma effluent, to further our understanding of this relationship. In addition, they propose examination of the exercise pressor response after directly inhibiting Na+/K+ pump with regional digoxin administration. This project will further increase their knowledge of the mechanisms regulating the muscle exercise pressor response, and may add to understanding of the role of this reflex in diseases such as CHF. The PI has been funded by an NRSA (F32 HL10320). This proposal will give the PI the additional support and training necessary to become an independent investigator. The mentor for this project has recently received a K24 Award and is the Program Director (PD) of their General Clinical Research Center (GCRC). Accordingly, he is ideally suited to serve in this capacity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PYCNOGENOL FOR TREATMENT OF ARM LYMPHEDEMA Principal Investigator & Institution: Hutson, Paul R.; Associate Professor; None; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 30-APR-2005 Summary: (provided by applicant): Lymphedema of the arm affects the function and self-image of approximately 600,000 of the 2 million breast cancer survivors in the United States. Chronic lymphedema can lead to recurrent infections and permanent swelling, in some cases impairing function. Although various methods of massage and the use of non-elastic compression "sleeves" have been shown to decrease the severity of lymphedema, these methods of physical therapy are limited in terms of patient acceptance, compliance, and by the availability of trained therapists. There is presently no pharmacologic treatment that has proven effective in treating or preventing the development of lymphedema in women treated for breast cancer. We propose a doubleblind, placebo-controlled trial of an extract of the bark of the French maritime pine tree (Pycnogenol(r)) as a treatment for arm lymphedema in breast cancer survivors. Pycnogenol(r) is widely used in Europe for lymphedema of the leg and varicose veins, and is thought to act by several mechanisms including vascular permeability and

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vascular constriction. The development of such a therapeutic approach would therefore constitute a major breakthrough in the treatment of this common symptom of breast cancer lymphedema. Bioelectric impedance is a painless, quick, and easily-performed method of estimating the extracellular and total water volume of the body or segment, such as the arm. We will compare the correlation of both a single- and a multiplefrequency bioelectric impedance instrument in measuring change in arm volume to a standard assessment using water displacement. We expect that bioelectric impedance will prove faster and more sensitive to changes in extracellular water (lymphedema) than the water displacement method. We also propose to use a small oral dose of midazolam and single blood sampling to screen for effects of Pycnogenol(r) on the activity of the common drug metabolizing enzyme CYP3A4. For those subjects who are already receiving digoxin, we will use digoxin urine excretion to screen for effects of the botanical upon the activity of P-glycoprotein. Finally, we will continue the evaluation of a new questionnaire of lymphedema symptoms presently being tested as a tool for assessing the severity and improvement of symptoms with treatment. In summary, the successful completion of this research can be expected to provide an alternative therapy and new instruments for treating and measuring lymphedema. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STRUCTURE AND FUNCTION OF X,K ATPASE FAMILY MEMBERS Principal Investigator & Institution: Modyanov, Nikolai N.; Medical College of Ohio at Toledo Research & Grants Admin. Toledo, Oh 436145804 Timing: Fiscal Year 2003; Project Start 17-MAR-2003; Project End 28-FEB-2008 Summary: (provided by applicant): The X,K-ATPases represent a family of structurally related but functionally distinct iontransporting ATPases including receptors for cardiac glycosides (Na,K-ATPase) and anti-ulcer drugs (gastric H,K-ATPase). Studies proposed in this project focus on the molecular aspects of the human nongastric H,K-ATPase, and the muscle-specific beta-m-protein, which is a novel memberof the X,K-ATPase family. Nongastric H,K-ATPase plays an important role in the maintenance of electrolyte homeostasis under pathophysiological conditions. Most significantly, this human ion pump is sensitive to cardiac glycosides, particularly to digoxin and digitoxin, which are widely used in clinical practice. During the previous funding period we have characterized basic ion-transport and catalytic functions of recombinant human nongastric H,K-ATPase via expression in Xenopus oocytes and insect cells. The objective of the first group of proposed studies is to define specific features of reaction mechanism of nongastric H,K-ATPase (Specific Aim 1) and to examine the roles of particular structural motifs and residues in the determination of ion specificity and inhibitor sensitivity of human nongastric H,K-ATPase (Specific Aim 2). The anticipated results should provide new insight into molecular basis of the human nongastric H,K-ATPase functioning and define relationship between members of X,K-ATPase family. The results of our preliminary studies demonstrated that recently identified muscle-specific betam protein exhibits structural features, cellular location and functional roles all of which are clearly different from those of the other X,K-ATPase beta subunits. The unique temporospatial expression pattern suggests that beta-m may play an essential role in development of heart and skeletal muscle. The hypothesis to be tested is that betam is associated in vivo with the protein(s) different from known X,K-ATPase alphasubunits, thus being a component of an unknown system, which might be an unidentified muscle-specific PATPase. The main objective of Specific Aim 3, is to identify protein counterpart(s) of the muscle specific beta-m. These experiments should

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clarify the relationship between the beta-m and other proteins in skeletal muscle and heart and provide insight into understanding the beta-m physiological function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: VAGINAL DRUG DELIVERY OF P-GLYCOPROTEIN SUBSTRATES Principal Investigator & Institution: Pauletti, Giovanni M.; Pharmaceutical Sciences; University of Cincinnati 2624 Clifton Ave Cincinnati, Oh 45221 Timing: Fiscal Year 2003; Project Start 10-APR-2003; Project End 31-MAR-2005 Summary: (provided by applicant): The long-term goal of our research is to improve systemic delivery of drugs with limited oral bioavailability due to extensive first-pass elimination by means of site-specific vaginal administration in the female. The central hypothesis of the present proposal is that progesterone regulates functional expression of P-glycoprotein (P-gp) in the vaginal mucosa leading to variable drug efflux. As a consequence, maximum vaginal bioavailability of P-gp substrates is restricted to a defined time window during the menstrual cycle. The MDR1 gene product P-gp is a prototype of membrane efflux systems that limit transcellular transport of drug molecules with broad specificity at strategic epithelial and endothelial membrane barriers, including the gastrointestinal mucosa. Thus, there are three specific aims proposed: (l) To test the hypothesis that progesterone regulates P-gp expression in human vaginal mucosa in vivo and in vitro. (2) To determine whether P-gp efflux activity in human vaginal epithelial cells in vitro is regulated by progesterone. (3) To test the prediction that progesterone regulates P-gp expression at the transcriptional level. Northern blot analysis will be conducted to quantify mRNA of P-gp in biopsies of human vaginal mucosa collected during the menstrual cycle as well as progesteronetreated immortalized human vaginal epithelial cells. Protein expression in response to cyclic hormonal changes will be determined by immunoblot analysis. Functional activity of P-gp will be assessed in vitro using intracellular accumulation of the P-gp substrate digoxin. Experiments will be designed to determine whether progesterone-induced changes in digoxin accumulation satisfy established criteria for P-gp-mediated efflux, including directionality, dependency on energy and substrate concentration, and sensitivity to selective inhibition. Finally, promoter/reporter constructs will be prepared to determine DNA sequences in the upstream region of the MDR1 gene that facilitate progesterone signaling. The significance of this research is that it will set the stage for future mechanistic studies to elucidate the interplay of female reproductive hormones in the regulation of vaginal P-gp. From the drug delivery point of view, the results may be applicable to determine an optimum time window during the menstrual cycle for effective vaginal delivery of P-gp substrates in order to maximize systemic bioavailability. 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

3

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

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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 “digoxin” (or synonyms) into the search box. This search gives you access to fulltext articles. The following is a sample of items found for digoxin in the PubMed Central database: •

Association between the number of coadministered P-glycoprotein inhibitors and serum digoxin levels in patients on therapeutic drug monitoring. by Englund G, Hallberg P, Artursson P, Michaelsson K, Melhus H.; 2004; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=411066

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Binding of Digitoxin and Some Related Cardenolides to Human Plasma Proteins. by Lukas DS, De Martino AG.; 1969 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=322318

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Digoxin Intoxication: the Relationship of Clinical Presentation to Serum Digoxin Concentration. by Smith TW, Haber E.; 1970 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=322739

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Double isotope dilution derivative assay of digitoxin in plasma, urine, and stool of patients maintained on the drug. by Lukas DA, Peterson RE.; 1966 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=292755

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Effect of quinidine on the digoxin receptor in vitro. by Ball WJ Jr, Tse-Eng D, Wallick ET, Bilezikian JP, Schwartz A, Butler VP Jr.; 1981 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=370894

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Effects of Digoxin-Specific Antibodies on Accumulation and Binding of Digoxin by Human Erythrocytes. by Gardner JD, Kiino DR, Swartz TJ, Butler VP Jr.; 1973 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=302462

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Effects of sheep digoxin-specific antibodies and their Fab fragments on digoxin pharmacokinetics in dogs. by Butler VP Jr, Schmidt DH, Smith TW, Haber E, Raynor BD, Demartini P.; 1977 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=333366

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Immunological Protection against Digoxin Toxicity. by Schmidt DH, Butler VP Jr.; 1971 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=292001

4

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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•

Interruption of the Enterohepatic Circulation of Digitoxin by Cholestyramine. I. PROTECTION AGAINST LETHAL DIGITOXIN INTOXICATION. by Caldwell JH, Greenberger NJ.; 1971 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=292212

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Interruption of the Enterohepatic Circulation of Digitoxin by Cholestyramine. II. EFFECT ON METABOLIC DISPOSITION OF TRITIUM-LABELED DIGITOXIN AND CARDIAC SYSTOLIC INTERVALS IN MAN. by Caldwell JH, Bush CA, Greenberger NJ.; 1971 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=292213

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Reduction of digoxin to 20R-dihydrodigoxin by cultures of Eubacterium lentum. by Robertson LW, Chandrasekaran A, Reuning RH, Hui J, Rawal BD.; 1986 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=239061

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Reductive inactivation of digitoxin by Eubacterium lentum cultures. by Chandrasekaran A, Robertson LW, Reuning RH.; 1987 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=203778

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Reversal of Advanced Digitoxin Toxicity and Modification of Pharmacokinetics by Specific Antibodies and Fab Fragments. by Ochs HR, Smith TW.; 1977 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=372486

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Reversal of Digoxin Toxicity with Specific Antibodies. by Schmidt DH, Butler VP Jr.; 1971 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=442074

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The effect of chronic digitoxin administration on the contractile state of normal and nonfailing hypertrophied myocardium. by Williams JF, Potter RD.; 1975 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=436557

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The Electrophysiologic Effects of Low and High Digoxin Concentrations on Isolated Mammalian Cardiac Tissue: Reversal by Digoxin-Specific Antibody. by Mandel WJ, Bigger JT Jr, Butler VP Jr.; 1972 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=292274

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THE INTERRELATIONSHIPS OF THE CARDIOVASCULAR, RENAL AND ELECTROLYTE EFFECTS OF INTRAVENOUS DIGOXIN IN CONGESTIVE HEART FAILURE. by Eichna LW, Farber SJ, Berger AR, Earle DP, Rader B, Pellegrino E, Albert RE, Alexander JD, Taube H, Youngwirth S.; 1951 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=436368

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The Measurement of Digitoxin in Human Serum by Radioimmunoassay. by Oliver GC Jr, Parker BM, Brasfield DL, Parker CW.; 1968 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=297256

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

A comparison between the effects of diltiazem and isosorbide dinitrate on digoxin pharmacodynamics and kinetics in the treatment of patients with chronic ischemic heart failure. Author(s): Mahgoub AA, El-Medany AH, Abdulatif AS. Source: Saudi Med J. 2002 June; 23(6): 725-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12070557

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A hypothalamic digoxin mediated model for conscious and subliminal perception. Author(s): Kumar AR, Kurup PA. Source: Journal of Neural Transmission (Vienna, Austria : 1996). 2001; 108(7): 855-68. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11515751

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A hypothalamic digoxin-mediated model for autism. Author(s): Kurup RK, Kurup PA. Source: The International Journal of Neuroscience. 2003 November; 113(11): 1537-59. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14585753

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A hypothalamic digoxin-mediated model for conscious and subliminal perception. Author(s): Kurup RK, Kurup PA. Source: The International Journal of Neuroscience. 2003 June; 113(6): 815-20. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12775345

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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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A new turbidometric digoxin immunoassay on the ADVIA 1650 analyzer is free from interference by spironolactone, potassium canrenoate, and their common metabolite canrenone. Author(s): Datta P, Dasgupta A. Source: Therapeutic Drug Monitoring. 2003 August; 25(4): 478-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12883233

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A prospective study of the clarithromycin-digoxin interaction in elderly patients. Author(s): Zapater P, Reus S, Tello A, Torrus D, Perez-Mateo M, Horga JF. Source: The Journal of Antimicrobial Chemotherapy. 2002 October; 50(4): 601-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12356809

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A single H:CDR3 residue in the anti-digoxin antibody 26-10 modulates specificity for C16-substituted digoxin analogs. Author(s): Short MK, Jeffrey PD, Demirjian A, Margolies MN. Source: Protein Engineering. 2001 April; 14(4): 287-96. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11391021

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Absence of a pharmacokinetic interaction between digoxin and levofloxacin. Author(s): Chien SC, Rogge MC, Williams RR, Natarajan J, Wong F, Chow AT. Source: Journal of Clinical Pharmacy and Therapeutics. 2002 February; 27(1): 7-12. Erratum In: J Clin Pharm Ther 2002 June; 27(3): 231. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11846857

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Absence of interaction of fondaparinux sodium with digoxin in healthy volunteers. Author(s): Mant T, Fournie P, Ollier C, Donat F, Necciari J. Source: Clinical Pharmacokinetics. 2002; 41 Suppl 2: 39-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12383044

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Acquired colour vision deficiency in patients receiving digoxin maintenance therapy. Author(s): Lawrenson JG, Kelly C, Lawrenson AL, Birch J. Source: The British Journal of Ophthalmology. 2002 November; 86(11): 1259-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12386084

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Activated charcoal is effective but equilibrium dialysis is ineffective in removing oleander leaf extract and oleandrin from human serum: monitoring the effect by measuring apparent digoxin concentration. Author(s): Dasgupta A, Cao S, Wells A. Source: Therapeutic Drug Monitoring. 2003 June; 25(3): 323-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12766561

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Activated charcoal safe and effective for digoxin toxicity. Author(s): Fee WH Jr. Source: The American Journal of Medicine. 2004 March 15; 116(6): 430. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15006596

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Acute ventricular rate control in atrial fibrillation: IV combination of diltiazem and digoxin vs. IV diltiazem alone. Author(s): Wattanasuwan N, Khan IA, Mehta NJ, Arora P, Singh N, Vasavada BC, Sacchi TJ. Source: Chest. 2001 February; 119(2): 502-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11171729

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Albumin-dependent digoxin transfer in isolated perfused human placenta. Author(s): Tsadkin M, Holcberg G, Sapir O, Hallak M, Huleihel M, Katz M, Polachek H, Mazor M, Ben-Zvi Z. Source: Int J Clin Pharmacol Ther. 2001 April; 39(4): 158-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11332871

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Amiodarone versus digoxin and metoprolol combination for the prevention of postcoronary bypass atrial fibrillation. Author(s): Tokmakoglu H, Kandemir O, Gunaydin S, Catav Z, Yorgancioglu C, Zorlutuna Y. Source: European Journal of Cardio-Thoracic Surgery : Official Journal of the European Association for Cardio-Thoracic Surgery. 2002 March; 21(3): 401-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11888754

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An alternative hypothesis to involvement of intestinal P-glycoprotein as the cause for digoxin oral bioavailability enhancement by talinolol. Author(s): Chiou WL, Ma C, Chung SM, Wu TC. Source: Clinical Pharmacology and Therapeutics. 2001 January; 69(1): 79-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11180042

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An autopsy case of combined drug intoxication involving verapamil, metoprolol and digoxin. Author(s): Kinoshita H, Taniguchi T, Nishiguchi M, Ouchi H, Minami T, Utsumi T, Motomura H, Tsuda T, Ohta T, Aoki S, Komeda M, Kamamoto T, Kubota A, Fuke C, Arao T, Miyazaki T, Hishida S. Source: Forensic Science International. 2003 April 23; 133(1-2): 107-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12742696

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Appropriateness of digoxin level monitoring. Author(s): Mordasini MR, Krahenbuhl S, Schlienger RG. Source: Swiss Medical Weekly : Official Journal of the Swiss Society of Infectious Diseases, the Swiss Society of Internal Medicine, the Swiss Society of Pneumology. 2002 September 7; 132(35-36): 506-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12506332

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Assessment of potential digoxin-rabeprazole interaction after formulary conversion of proton-pump inhibitors. Author(s): Le GH, Schaefer MG, Plowman BK, Morreale AP, Delattre M, Okino L, Felicio L. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 2003 July 1; 60(13): 1343-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12901036

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Association of serum digoxin concentration and outcomes in patients with heart failure. Author(s): Rathore SS, Curtis JP, Wang Y, Bristow MR, Krumholz HM. Source: Jama : the Journal of the American Medical Association. 2003 February 19; 289(7): 871-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12588271

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Beta-blockade and binding of digoxin to skeletal muscle. Author(s): Joreteg T, Jogestrand T. Source: Clinical Physiology (Oxford, England). 1986 April; 6(2): 183-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3006980

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Beta-methyl digoxin: a better absorbable digoxin. Author(s): Das G. Source: Int J Clin Pharmacol Ther Toxicol. 1989 November; 27(11): 521-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2693372

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Bidirectional (positive/negative) interference in a digoxin immunoassay: importance of antibody specificity. Author(s): Datta P, Dasgupta A. Source: Therapeutic Drug Monitoring. 1998 June; 20(3): 352-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9631936

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Bidirectional (positive/negative) interference of spironolactone, canrenone, and potassium canrenoate on serum digoxin measurement: elimination of interference by measuring free digoxin or using a chemiluminescent assay for digoxin. Author(s): Dasgupta A, Saffer H, Wells A, Datta P. Source: Journal of Clinical Laboratory Analysis. 2002; 16(4): 172-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12112389

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Bidirectional tachycardia associated with digoxin toxicity. Author(s): Chan T, Vilke GM, Williams S. Source: The Journal of Emergency Medicine. 1995 January-February; 13(1): 89. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7782630

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Bidirectional ventricular tachycardia resulting from digoxin and amiodarone treatment of rapid atrial fibrillation. Author(s): Lien WC, Huang CH, Chen WJ. Source: The American Journal of Emergency Medicine. 2004 May; 22(3): 235-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15138971

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Binding of digoxin to slow- and fast-twitch skeletal muscle fibres. Author(s): Joreteg T. Source: Clinical Physiology (Oxford, England). 1986 August; 6(4): 357-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3742955

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Bioanalysis of digoxin and its metabolites using direct serum injection combined with liquid chromatography and on-line immunochemical detection. Author(s): Oosterkamp AJ, Irth H, Beth M, Unger KK, Tjaden UR, van de Greef J. Source: Journal of Chromatography. B, Biomedical Applications. 1994 February 18; 653(1): 55-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8012560

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Bioavailability of digoxin tablets in healthy volunteers. Author(s): Lee CH, Park YJ, Sands CD, Jones DW, Trang JM. Source: Arch Pharm Res. 1994 April; 17(2): 80-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10319136

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Calcium for hyperkalaemia in digoxin toxicity. Author(s): Davey M. Source: Emergency Medicine Journal : Emj. 2002 March; 19(2): 183. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11904281

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Capillary electrophoretic immunoassays for digoxin and gentamicin with laserinduced fluorescence polarization detection. Author(s): Wan QH, Le XC. Source: J Chromatogr B Biomed Sci Appl. 1999 October 29; 734(1): 31-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10574187

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Carvedilol alone or in combination with digoxin for the management of atrial fibrillation in patients with heart failure? Author(s): Khand AU, Rankin AC, Martin W, Taylor J, Gemmell I, Cleland JG. Source: Journal of the American College of Cardiology. 2003 December 3; 42(11): 194451. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14662257

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Cilomilast: pharmacokinetic and pharmacodynamic interactions with digoxin. Author(s): Zussman BD, Kelly J, Murdoch RD, Clark DJ, Mbchb, Schubert C, Collie H. Source: Clinical Therapeutics. 2001 June; 23(6): 921-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11440291

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Clarithromycin-induced digoxin toxicity: a case report and a review of the literature. Author(s): Xu H, Rashkow A. Source: Conn Med. 2001 September; 65(9): 527-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11678058

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Clinical benefits of low serum digoxin concentrations in heart failure. Author(s): Adams KF Jr, Gheorghiade M, Uretsky BF, Patterson JH, Schwartz TA, Young JB. Source: Journal of the American College of Cardiology. 2002 March 20; 39(6): 946-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11897434

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Clopidogrel, a novel antiplatelet agent, and digoxin: absence of pharmacodynamic and pharmacokinetic interaction. Author(s): Peeters PA, Crijns HJ, Tamminga WJ, Jonkman JH, Dickinson JP, Necciari J. Source: Seminars in Thrombosis and Hemostasis. 1999; 25 Suppl 2: 51-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10440424

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Coadministration of digoxin with itraconazole in renal transplant recipients. Author(s): Mathis AS, Friedman GS. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 2001 February; 37(2): E18. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11157404

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Comment: clarithromycin-digoxin interaction. Author(s): Juurlink DN, Ito S. Source: The Annals of Pharmacotherapy. 1999 December; 33(12): 1375-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10630847

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Comparable effects of DIGIBIND and DigiFab in thirteen digoxin immunoassays. Author(s): McMillin GA, Owen WE, Lambert TL, De BK, Frank EL, Bach PR, Annesley TM, Roberts WL. Source: Clinical Chemistry. 2002 September; 48(9): 1580-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12194938

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Comparing the toxicity of digoxin and digitoxin in a geriatric population: should an old drug be rediscovered? Author(s): Roever C, Ferrante J, Gonzalez EC, Pal N, Roetzheim RG. Source: Southern Medical Journal. 2000 February; 93(2): 199-202. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10701788

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Comparison between propafenone and digoxin administered intravenously to patients with acute atrial fibrillation. PAFIT-3 Investigators. The Propafenone in Atrial Fibrillation Italian Trial. Author(s): Bianconi L, Mennuni M. Source: The American Journal of Cardiology. 1998 September 1; 82(5): 584-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9732884

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Comparison of class III antiarrhythmic drugs versus digoxin for the reversion of newonset atrial fibrillation. Author(s): Veloso HH. Source: Annals of Emergency Medicine. 2001 June; 37(6): 735-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11385352

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Comparison of digoxin versus low-dose amiodarone for ventricular rate control in patients with chronic atrial fibrillation. Author(s): Tse HF, Lam YM, Lau CP, Cheung BM, Kumana CR. Source: Clinical and Experimental Pharmacology & Physiology. 2001 May-June; 28(5-6): 446-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11380520

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Concomitant digoxin toxicity and warfarin interaction in a patient receiving clarithromycin. Author(s): Gooderham MJ, Bolli P, Fernandez PG. Source: The Annals of Pharmacotherapy. 1999 July-August; 33(7-8): 796-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10466907

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Concurrent administration of donepezil HCl and digoxin: assessment of pharmacokinetic changes. Author(s): Tiseo PJ, Perdomo CA, Friedhoff LT. Source: British Journal of Clinical Pharmacology. 1998 November; 46 Suppl 1: 40-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9839765

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Contemporary utilization of digoxin in patients with atrial fibrillation. Clinical Quality Improvement Network Investigators. Author(s): McAlister FA, Ackman ML, Tsuyuki RT, Kimber S, Teo KK. Source: The Annals of Pharmacotherapy. 1999 March; 33(3): 289-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10200851

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Contribution of increased oral bioavailability and reduced nonglomerular renal clearance of digoxin to the digoxin-clarithromycin interaction. Author(s): Rengelshausen J, Goggelmann C, Burhenne J, Riedel KD, Ludwig J, Weiss J, Mikus G, Walter-Sack I, Haefeli WE. Source: British Journal of Clinical Pharmacology. 2003 July; 56(1): 32-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12848773

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Controlling the effectiveness of digoxin. Author(s): Krohn BG. Source: Journal of the American College of Cardiology. 2002 August 21; 40(4): 836; Author Reply 836-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12204522

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Determination of the cardiac glycosides digoxin and digitoxin by liquid chromatography combined with isotope-dilution mass spectrometry (LC-IDMS)--a candidate reference measurement procedure. Author(s): Kaiser P, Kramer U, Meissner D, Kress M, Wood WG, Reinauer H. Source: Clin Lab. 2003; 49(7-8): 329-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12908733

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Development of bradycardia during sedation with dexmedetomidine in an infant concurrently receiving digoxin. Author(s): Berkenbosch JW, Tobias JD. Source: Pediatric Critical Care Medicine : a Journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies. 2003 April; 4(2): 203-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12749653

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Digoxin and quality of life in heart failure. Author(s): Curtis JP, Rathore SS. Source: Journal of Cardiac Failure. 2003 August; 9(4): 345; Author Reply 345. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=13680556

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Digoxin antibody decreases natriuresis and diuresis in cerebral hemorrhage. Author(s): Menezes JC, Troster EJ, Dichtchekenian V. Source: Intensive Care Medicine. 2003 December; 29(12): 2291-6. Epub 2003 September 03. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12955184

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Digoxin for the treatment of heart failure. Author(s): Hallberg P, Michaelsson K, Melhus H. Source: The New England Journal of Medicine. 2003 February 13; 348(7): 661-3; Author Reply 661-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12587575

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Digoxin for the treatment of heart failure. Author(s): Hudson M, Pilote L. Source: The New England Journal of Medicine. 2003 February 13; 348(7): 661-3; Author Reply 661-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12587574

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Digoxin for the treatment of heart failure. Author(s): Moulias S, Tigoulet F, Meaume S. Source: The New England Journal of Medicine. 2003 February 13; 348(7): 661-3; Author Reply 661-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12584380

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Digoxin in heart failure and cardiac arrhythmias. Author(s): Campbell TJ, MacDonald PS. Source: The Medical Journal of Australia. 2003 July 21; 179(2): 98-102. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12864722

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Digoxin in heart failure. Author(s): Spencer AP. Source: Critical Care Nursing Clinics of North America. 2003 December; 15(4): 447-52. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14717389

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Digoxin intoxication: arrhythmogenic or antiarrhythmic? Author(s): Siniorakis E, Arvanitakis S, Ralli D, Ciubotariou-Petsa I, Barbis C, Bonoris P. Source: International Journal of Cardiology. 2003 September; 91(1): 111-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12957740

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Digoxin pharmacokinetics and MDR1 genetic polymorphisms. Author(s): Verstuyft C, Schwab M, Schaeffeler E, Kerb R, Brinkmann U, Jaillon P, FunckBrentano C, Becquemont L. Source: European Journal of Clinical Pharmacology. 2003 April; 58(12): 809-12. Epub 2003 March 01. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12698307

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Digoxin remains useful in the management of chronic heart failure. Author(s): Dec GW. Source: The Medical Clinics of North America. 2003 March; 87(2): 317-37. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12693728

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Digoxin therapeutic drug monitoring: an audit and review. Author(s): Sidwell A, Barclay M, Begg E, Moore G. Source: N Z Med J. 2003 December 12; 116(1187): U708. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14752536

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Digoxin therapy and the risk of primary cardiac arrest in patients with congestive heart failure: effect of mild-moderate renal impairment. Author(s): Rea TD, Siscovick DS, Psaty BM, Pearce RM, Raghunathan TE, Whitsel EA, Cobb LA, Weinmann S, Anderson GD, Arbogast P, Lin D. Source: Journal of Clinical Epidemiology. 2003 July; 56(7): 646-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12921933

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Digoxin therapy for heart failure: safe for women? Author(s): Rathore SS, Krumholz HM. Source: Ital Heart J. 2003 March; 4(3): 148-51. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12784740

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Digoxin toxicity and ritonavir: a drug interaction mediated through p-glycoprotein? Author(s): Phillips EJ, Rachlis AR, Ito S. Source: Aids (London, England). 2003 July 4; 17(10): 1577-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12824804

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Digoxin toxicity in Thai medical patients: clinical manifestations and an appropriate diagnostic serum level. Author(s): Jitapunkul S, Kongsawat V, Sutheparak S. Source: Southeast Asian J Trop Med Public Health. 2002 September; 33(3): 608-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12693599

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Digoxin up-regulates multidrug resistance transporter (MDR1) mRNA and simultaneously down-regulates steroid xenobiotic receptor mRNA. Author(s): Takara K, Takagi K, Tsujimoto M, Ohnishi N, Yokoyama T. Source: Biochemical and Biophysical Research Communications. 2003 June 20; 306(1): 116-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12788075

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Digoxin-carvedilol interactions in children. Author(s): Ratnapalan S, Griffiths K, Costei AM, Benson L, Koren G. Source: The Journal of Pediatrics. 2003 May; 142(5): 572-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12756393

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Digoxin-like immunoreactive substance in nonoliguric hyperkalemia of the premature infant. Author(s): Mildenberger E, Oels K, Bauer K, Paul M, Versmold HT. Source: Biology of the Neonate. 2003; 83(3): 182-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12660435

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Effect of age on mortality, hospitalizations and response to digoxin in patients with heart failure: the DIG study. Author(s): Rich MW, McSherry F, Williford WO, Yusuf S; Digitalis Investigation Group. Source: Journal of the American College of Cardiology. 2001 September; 38(3): 806-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11527638

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Effect of clarithromycin on steady-state digoxin concentrations. Author(s): Tanaka H, Matsumoto K, Ueno K, Kodama M, Yoneda K, Katayama Y, Miyatake K. Source: The Annals of Pharmacotherapy. 2003 February; 37(2): 178-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12549942

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Effect of digoxin on the somatotroph responsiveness to growth hormone-releasing hormone (GHRH) alone or combined with arginine in normal young volunteers. Author(s): Broglio F, Benso A, Gottero C, Vito LD, Granata R, Arvat E, Bobbio M, Trevi G, Ghigo E. Source: Clinical Endocrinology. 2001 December; 55(6): 755-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11895217

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Effect of garenoxacin on eubacteria in the normal intestinal microflora when administered concomitantly with digoxin. Author(s): Nord CE, Meurling L, Russo RL, Bello A, Grasela DM, Gajjar DA. Source: J Chemother. 2003 June; 15(3): 244-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12868550

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Effect of gentamicin on serum digoxin level in patients with congestive heart failure. Author(s): Alkadi HO, Nooman MA, Raja'a YA. Source: Pharmacy World & Science : Pws. 2004 April; 26(2): 107-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15085946

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Effect of grapefruit juice on digoxin pharmacokinetics in humans. Author(s): Becquemont L, Verstuyft C, Kerb R, Brinkmann U, Lebot M, Jaillon P, FunckBrentano C. Source: Clinical Pharmacology and Therapeutics. 2001 October; 70(4): 311-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11673746

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Effects of 2-hydroxypropyl-beta-cyclodextrin on pharmacokinetics of digoxin in rabbits and humans. Author(s): He ZG, Li YS, Zhang TH, Tang X, Zhao C, Zhang RH. Source: Pharmazie. 2004 March; 59(3): 200-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15074593

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Effects of continuous exposure to digoxin on MDR1 function and expression in Caco2 cells. Author(s): Takara K, Tsujimoto M, Ohnishi N, Yokoyama T. Source: The Journal of Pharmacy and Pharmacology. 2003 May; 55(5): 675-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12831511

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Effects of digoxin on left atrial function in heart failure. Author(s): Dernellis JM, Panaretou MP. Source: Heart (British Cardiac Society). 2003 November; 89(11): 1308-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14594886

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Effects of digoxin, furosemide, enalaprilat and metoprolol on endothelial function in young normotensive subjects. Author(s): Muhlen BV, Millgard J, Lind L. Source: Clinical and Experimental Pharmacology & Physiology. 2001 May-June; 28(5-6): 381-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11380510

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Effects of grapefruit juice on intestinal P-glycoprotein: evaluation using digoxin in humans. Author(s): Parker RB, Yates CR, Soberman JE, Laizure SC. Source: Pharmacotherapy. 2003 August; 23(8): 979-87. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12921244

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Effects of the concomitant administration of tamsulosin (0.8 mg) on the pharmacokinetic and safety profile of intravenous digoxin (Lanoxin) in normal healthy subjects: a placebo-controlled evaluation. Author(s): Miyazawa Y, Paul Starkey L, Forrest A, Schentag JJ, Kamimura H, Swarz H, Ito Y. Source: Journal of Clinical Pharmacy and Therapeutics. 2002 February; 27(1): 13-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11846858

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Endogenous digoxin, hemispheric dominance and family bonding behavior. Author(s): Kurup RK, Kurup PA. Source: Neurological Research. 2003 June; 25(4): 401-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12870268

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Fab treatment in acute digitalis intoxication: reliability of serum digoxin determination with the Stratus system. Author(s): Bizzaro N, Finco B, Milani L. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 1993 August 31; 217(2): 225-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8261633

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Factors affecting digoxin action and kinetics. Author(s): Hartshorn EA, Hartshorn JC. Source: The Journal of Cardiovascular Nursing. 1988 August; 2(4): 12-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3392556

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Factors affecting the clinical response to treatment with digoxin and two calcium antagonists in patients with atrial fibrillation. Author(s): Lewis RV, McDevitt DG. Source: British Journal of Clinical Pharmacology. 1988 May; 25(5): 603-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3044426

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Factors influencing the prediction of steady state concentrations of digoxin. Author(s): Nakamura T, Kakumoto M, Yamashita K, Takara K, Tanigawara Y, Sakaeda T, Okumura K. Source: Biological & Pharmaceutical Bulletin. 2001 April; 24(4): 403-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11305603

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Falsely elevated digoxin level of 45.9 ng/mL due to interference from human antimouse antibody. Author(s): Ingels M, Rangan C, Morfin JP, Williams SR, Clark RF. Source: Journal of Toxicology. Clinical Toxicology. 2000; 38(3): 343-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10866338

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Falsely elevated digoxin levels: another look. Author(s): Longley JM, Murphy JE. Source: Therapeutic Drug Monitoring. 1989 September; 11(5): 572-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2815233

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Falsely elevated serum digoxin levels secondary to endogenous digoxin-like immunoreactive substances. Author(s): Koobatian TJ, Roberts JR. Source: Academic Emergency Medicine : Official Journal of the Society for Academic Emergency Medicine. 1995 April; 2(4): 322-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11727693

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False-positive serum digoxin concentrations determined by three digoxin assays in patients with liver disease. Author(s): Frisolone J, Sylvia LM, Gelwan J, Pal S, Pellechia C. Source: Clin Pharm. 1988 June; 7(6): 444-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3402179

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Fatal digoxin poisoning: an unsuccessful resuscitation with use of digoxin-immune Fab. Author(s): Rose SR, Gorman RL, McDaniel J. Source: The American Journal of Emergency Medicine. 1987 November; 5(6): 509-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3663292

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Fatal non-occlusive mesenteric infarction following digoxin intoxication. Author(s): Guglielminotti J, Tremey B, Maury E, Alzieu M, Offenstadt G. Source: Intensive Care Medicine. 2000 June; 26(6): 829. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10945415

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FDA approves digoxin-toxicity remedy. Author(s): Thompson CA. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 2001 November 1; 58(21): 2021. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11715821

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Fetal death after successful conversion of fetal supraventricular tachycardia with digoxin and verapamil. Author(s): Owen J, Colvin EV, Davis RO. Source: American Journal of Obstetrics and Gynecology. 1988 May; 158(5): 1169-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3369500

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Flecainide compared with a combination of digoxin and disopyramide for acute atrial arrhythmias after cardiopulmonary bypass. Author(s): Gavaghan TP, Koegh AM, Kelly RP, Campbell TJ, Thorburn C, Morgan JJ. Source: British Heart Journal. 1988 December; 60(6): 497-501. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3146989

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Fluorescein interference in digoxin assay: an isolated case? Author(s): Paterson JR, Weston R, Blackie R, Neithercut WD. Source: Annals of Clinical Biochemistry. 1991 May; 28 ( Pt 3): 314-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1872583

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Free and total serum digoxin concentrations in a renal failure patient after treatment with digoxin immune Fab. Author(s): Clifton GD, McIntyre WJ, Zannikos PN, Harrison MR, Chandler MH. Source: Clin Pharm. 1989 June; 8(6): 441-5. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2743737

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Frequency of recurrence among infants with supraventricular tachycardia and comparison of recurrence rates among those with and without preexcitation and among those with and without response to digoxin and/or propranolol therapy. Author(s): Tortoriello TA, Snyder CS, Smith EO, Fenrich AL Jr, Friedman RA, Kertesz NJ. Source: The American Journal of Cardiology. 2003 November 1; 92(9): 1045-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14583354

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From digoxin to angiotensin-converting enzyme inhibitors: issues in pharmacotherapy for congestive heart failure. Author(s): Hackenbruck HA. Source: Clin Excell Nurse Pract. 2000 July; 4(4): 197-204. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11261079

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Generalised chorea due to digoxin toxicity. Author(s): Mulder LJ, van der Mast RC, Meerwaldt JD. Source: British Medical Journal (Clinical Research Ed.). 1988 April 30; 296(6631): 1262. Erratum In: Br Med J (Clin Res Ed) 1988 August 20-27; 297(6647): 562. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3382897

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Geographic differences in digoxin inactivation, a metabolic activity of the human anaerobic gut flora. Author(s): Mathan VI, Wiederman J, Dobkin JF, Lindenbaum J. Source: Gut. 1989 July; 30(7): 971-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2759492

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Gitoxin--a challenger for digoxin? Author(s): Pellegrin P, Lesne M. Source: Drug Intell Clin Pharm. 1985 December; 19(12): 945-6. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4085356

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Glucose uptake and binding of digoxin to skeletal muscle. Author(s): Joreteg T, Efendic S, Jogestrand T. Source: Clinical Physiology (Oxford, England). 1986 April; 6(2): 191-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2869857

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Hypothalamic digoxin and hemispheric chemical dominance in relation to the pathogenesis of bronchial asthma. Author(s): Kurup RK, Kurup PA. Source: The International Journal of Neuroscience. 2003 August; 113(8): 1143-59. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12888427

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Hypothalamic digoxin and hemispheric chemical dominance: relation to alcoholic addiction, alcoholic cirrhosis, and acquired hepatocerebral degeneration. Author(s): Kurup RK, Kurup PA. Source: The International Journal of Neuroscience. 2003 August; 113(8): 1105-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12888425

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Hypothalamic digoxin and isoprenoid pathway dysfunction relation to alcoholic addiction, alcoholic cirrhosis, and acquired hepatocerebral degeneration--relation to hemispheric chemical dominance. Author(s): Kurup RK, Kurup PA. Source: The International Journal of Neuroscience. 2003 April; 113(4): 547-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12856482

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Hypothalamic digoxin, cerebral chemical dominance, and calcium/magnesium metabolism. Author(s): Kurup RK, Kurup PA. Source: The International Journal of Neuroscience. 2003 July; 113(7): 999-1004. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12881191

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Hypothalamic digoxin, cerebral chemical dominance, and nitric oxide synthesis. Author(s): Kurup RK, Kurup PA. Source: Archives of Andrology. 2003 July-August; 49(4): 281-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12851030

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Hypothalamic digoxin, hemispheric chemical dominance and syndrome X with multiple lacunar state. A hypothesis. Author(s): Kurup RK, Kurup PA. Source: Neurological Research. 2003 October; 25(7): 739-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14579792

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Hypothalamic digoxin, hemispheric chemical dominance, and Alzheimer's disease. Author(s): Kurup RK, Kurup PA. Source: The International Journal of Neuroscience. 2003 March; 113(3): 361-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12803139

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Hypothalamic digoxin, hemispheric chemical dominance, and chronic bronchitis emphysema. Author(s): Kurup RK, Kurup PA. Source: The International Journal of Neuroscience. 2003 September; 113(9): 1241-58. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12959742

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Hypothalamic digoxin, hemispheric chemical dominance, and creativity. Author(s): Kurup RK, Kurup PA. Source: The International Journal of Neuroscience. 2003 April; 113(4): 565-77. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12856483

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Hypothalamic digoxin, hemispheric chemical dominance, and eating behavior. Author(s): Kurup RK, Kurup PA. Source: The International Journal of Neuroscience. 2003 August; 113(8): 1127-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12888426

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Hypothalamic digoxin, hemispheric chemical dominance, and inflammatory bowel disease. Author(s): Kurup RK, Kurup PA. Source: The International Journal of Neuroscience. 2003 September; 113(9): 1221-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12959741

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Hypothalamic digoxin, hemispheric chemical dominance, and interstitial lung disease. Author(s): Kurup RK, Kurup PA. Source: The International Journal of Neuroscience. 2003 October; 113(10): 1427-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14534040

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Hypothalamic digoxin, hemispheric chemical dominance, and mesenteric artery occlusion. Author(s): Kurup RK, Kurup PA. Source: The International Journal of Neuroscience. 2003 December; 113(12): 1741-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14602545

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Hypothalamic digoxin, hemispheric chemical dominance, and oncogenesis: evidence from multiple myeloma. Author(s): Kurup RK, Kurup PA. Source: The International Journal of Neuroscience. 2003 December; 113(12): 1719-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14602544

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Hypothalamic digoxin, hemispheric chemical dominance, and peptic ulcer disease. Author(s): Kurup RK, Kurup PA. Source: The International Journal of Neuroscience. 2003 October; 113(10): 1395-412. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14534038

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Hypothalamic digoxin, hemispheric chemical dominance, and sarcoidosis. Author(s): Kurup RK, Kurup PA. Source: The International Journal of Neuroscience. 2003 November; 113(11): 1593-611. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14585756

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Hypothalamic digoxin, hemispheric chemical dominance, and sleep. Author(s): Kurup RK, Kurup PA. Source: The International Journal of Neuroscience. 2003 April; 113(4): 537-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12856481

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Hypothalamic digoxin, hemispheric dominance, and family bonding behavior. Author(s): Kurup RK, Kurup PA. Source: The International Journal of Neuroscience. 2003 July; 113(7): 989-98. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12881190

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Hypothalamic digoxin-mediated model for Parkinson's disease. Author(s): Kurup RK, Kurup PA. Source: The International Journal of Neuroscience. 2003 April; 113(4): 515-36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12856480

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Immediate control of life-threatening digoxin intoxication in a child by use of digoxin-specific antibody fragments (Fab). Author(s): Husby P, Farstad M, Brock-Utne JG, Koller ME, Segadal L, Lund T, Ohm OJ. Source: Paediatric Anaesthesia. 2003 July; 13(6): 541-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12846714

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Improved sensitivity of digoxin assay by modification of the EMIT 2000 method. Author(s): Radembino N, Poirier JM, Ragueneau I, Jaillon P. Source: Therapeutic Drug Monitoring. 1999 April; 21(2): 256-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10217349

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Inappropriate use of digoxin in older hospitalized heart failure patients. Author(s): Ahmed A, Allman RM, DeLong JF. Source: The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 2002 February; 57(2): M138-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11818435

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Inappropriate use of digoxin in the elderly: how widespread is the problem and how can it be solved? Author(s): Haas GJ, Young JB. Source: Drug Safety : an International Journal of Medical Toxicology and Drug Experience. 1999 March; 20(3): 223-30. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10221852

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Increased glucose intolerance related to digoxin treatment in patients with type 2 diabetes mellitus. Author(s): Spigset O, Mjorndal T. Source: Journal of Internal Medicine. 1999 October; 246(4): 419-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10583713

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Inhibitory effect of digoxin on testosterone secretion through mechanisms involving decreases of cyclic AMP production and cytochrome P450scc activity in rat testicular interstitial cells. Author(s): Lin H, Wang SW, Tsai SC, Chen JJ, Chiao YC, Lu CC, Huang WJ, Wang GJ, Chen CF, Wang PS. Source: British Journal of Pharmacology. 1998 December; 125(8): 1635-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9886754

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Inotropic effect of digoxin in humans: mechanistic pharmacokinetic/pharmacodynamic model based on slow receptor binding. Author(s): Weiss M, Kang W. Source: Pharmaceutical Research. 2004 February; 21(2): 231-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15032303

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Interaction of digoxin with antihypertensive drugs via MDR1. Author(s): Takara K, Kakumoto M, Tanigawara Y, Funakoshi J, Sakaeda T, Okumura K. Source: Life Sciences. 2002 February 15; 70(13): 1491-500. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11895100

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Interference of endogenous digoxin-like immunoreactive factors in serum digoxin measurement is minimized in a new turbidimetric digoxin immunoassay on ADVIA 1650 analyzer. Author(s): Datta P, Dasgupta A. Source: Therapeutic Drug Monitoring. 2004 February; 26(1): 85-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14749555

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Intoxication due to negative canrenone interference in digoxin drug monitoring. Author(s): Steimer W, Muller C, Eber B, Emmanuilidis K. Source: Lancet. 1999 October 2; 354(9185): 1176-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10513714

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Intravenously administered digoxin in patients with acute atrial fibrillation: a population pharmacokinetic/pharmacodynamic analysis based on the Digitalis in Acute Atrial Fibrillation trial. Author(s): Hornestam B, Jerling M, Karlsson MO, Held P; DAAf Trial Group. Source: European Journal of Clinical Pharmacology. 2003 March; 58(11): 747-55. Epub 2003 February 19. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12634981

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Investigation of the interaction between argatroban and acetaminophen, lidocaine, or digoxin. Author(s): Inglis AM, Sheth SB, Hursting MJ, Tenero DM, Graham AM, DiCicco RA. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 2002 July 1; 59(13): 1258-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12116891

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Is digoxin a designer oestrogen? Author(s): Schussheim DH, Schussheim AE. Source: Lancet. 1998 June 6; 351(9117): 1734. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9734913

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Isolation and characterization of a digoxin transporter and its rat homologue expressed in the kidney. Author(s): Mikkaichi T, Suzuki T, Onogawa T, Tanemoto M, Mizutamari H, Okada M, Chaki T, Masuda S, Tokui T, Eto N, Abe M, Satoh F, Unno M, Hishinuma T, Inui K, Ito S, Goto J, Abe T. Source: Proceedings of the National Academy of Sciences of the United States of America. 2004 March 9; 101(10): 3569-74. Epub 2004 Mar 01. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14993604

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Isolation and characterization of human monoclonal antibodies to digoxin. Author(s): Ball WJ Jr, Kasturi R, Dey P, Tabet M, O'Donnell S, Hudson D, Fishwild D. Source: Journal of Immunology (Baltimore, Md. : 1950). 1999 August 15; 163(4): 2291-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10438974

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Kinetics of digoxin and anti-digoxin antibody fragments during treatment of digoxin toxicity. Author(s): Sinclair AJ, Hewick DS, Johnston PC, Stevenson IH, Lemon M. Source: British Journal of Clinical Pharmacology. 1989 September; 28(3): 352-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2789929

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Kinetics of the Fab fragments of digoxin antibodies and of bound digoxin in patients with severe digoxin intoxication. Author(s): Schaumann W, Kaufmann B, Neubert P, Smolarz A. Source: European Journal of Clinical Pharmacology. 1986; 30(5): 527-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3758140

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Lack of citalopram effect on oral digoxin pharmacokinetics. Author(s): Larsen F, Priskorn M, Overo KF. Source: Journal of Clinical Pharmacology. 2001 March; 41(3): 340-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11269575

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Lack of clinically significant interference by spironolactone with the AxSym Digoxin II assay. Author(s): Howard G, Barclay M, Florkowski C, Moore G, Roche A. Source: Therapeutic Drug Monitoring. 2003 February; 25(1): 112-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12548154

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Lack of effect of aprepitant on digoxin pharmacokinetics in healthy subjects. Author(s): Feuring M, Lee Y, Orlowski LH, Michiels N, De Smet M, Majumdar AK, Petty KJ, Goldberg MR, Murphy MG, Gottesdiener KM, Hesney M, Brackett LE, Wehling M. Source: Journal of Clinical Pharmacology. 2003 August; 43(8): 912-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12953348

Studies

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Lack of effect of eprosartan on the single dose pharmacokinetics of orally administered digoxin in healthy male volunteers. Author(s): Martin DE, Tompson D, Boike SC, Tenero D, Ilson B, Citerone D, Jorkasky DK. Source: British Journal of Clinical Pharmacology. 1997 June; 43(6): 661-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9205830

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Lack of effect of mizolastine on the safety and pharmacokinetics of digoxin administered orally in repeated doses to healthy volunteers. Author(s): Chaufour S, Le Coz F, Denolle T, Dubruc C, Cimarosti I, Deschamps C, Ulliac N, Delhotal-Landes B, Rosenzweig P. Source: Int J Clin Pharmacol Ther. 1998 May; 36(5): 286-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9629994

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Lack of interaction between pantoprazole and digoxin at therapeutic doses in man. Author(s): Hartmann M, Huber R, Bliesath H, Steinijans VW, Koch HJ, Wurst W, Kunz K. Source: Int J Clin Pharmacol Ther. 1996 May; 34(1 Suppl): S67-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8793605

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Lack of interaction between pantoprazole and digoxin at therapeutic doses in man. Author(s): Hartmann M, Huber R, Bliesath H, Steinijans VW, Koch HJ, Wurst W, Kunz K. Source: Int J Clin Pharmacol Ther. 1995 September; 33(9): 481-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8520804

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Lack of interaction between valaciclovir, the L-valyl ester of aciclovir, and digoxin. Author(s): Soul-Lawton JH, Weatherley BC, Posner J, Layton G, Peck RW. Source: British Journal of Clinical Pharmacology. 1998 January; 45(1): 87-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9489600

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Lack of interaction of digoxin and P-glycoprotein inhibitors, quinidine and verapamil in human placenta in vitro. Author(s): Holcberg G, Sapir O, Tsadkin M, Huleihel M, Lazer S, Katz M, Mazor M, BenZvi Z. Source: European Journal of Obstetrics, Gynecology, and Reproductive Biology. 2003 August 15; 109(2): 133-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12860328

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Lack of kinetic interaction between digoxin and voglibose. Author(s): Kusumoto M, Ueno K, Fujimura Y, Kameda T, Mashimo K, Takeda K, Tatami R, Shibakawa M. Source: European Journal of Clinical Pharmacology. 1999 March; 55(1): 79-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10206090

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Lack of mutual pharmacokinetic interaction between cerivastatin, a new HMG-CoA reductase inhibitor, and digoxin in healthy normocholesterolemic volunteers. Author(s): Weber P, Lettieri JT, Kaiser L, Mazzu AL. Source: Clinical Therapeutics. 1999 September; 21(9): 1563-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10509851

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Lack of pharmacokinetic interaction between gemifloxacin and digoxin in healthy elderly volunteers. Author(s): Vousden M, Allen A, Lewis A, Ehren N. Source: Chemotherapy. 1999 November-December; 45(6): 485-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10567779

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Late rebound digoxin toxicity after digoxin-specific antibody Fab fragments therapy in anuric patient. Author(s): Mycyk MB, Bryant SM, Cumpston KL. Source: The Journal of Emergency Medicine. 2003 January; 24(1): 91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12554051

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Late rebound digoxin toxicity after digoxin-specific antibody Fab fragments therapy in anuric patient. Author(s): Mehta RN, Mehta NJ, Gulati A. Source: The Journal of Emergency Medicine. 2002 February; 22(2): 203-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11858929

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Loading dose of digoxin. Author(s): Barbey JT, Donahue SR. Source: Jama : the Journal of the American Medical Association. 1997 February 19; 277(7): 518. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9032144

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Longitudinal assessment of a P-glycoprotein-mediated drug interaction of valspodar on digoxin. Author(s): Kovarik JM, Rigaudy L, Guerret M, Gerbeau C, Rost KL. Source: Clinical Pharmacology and Therapeutics. 1999 October; 66(4): 391-400. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10546923

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Long-term digoxin therapy. Author(s): Goldsmith SR. Source: Journal of the American College of Cardiology. 1995 September; 26(3): 838. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7642880

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Long-term use of K-strophanthin in advanced congestive heart failure due to dilated cardiomyopathy: a double-blind crossover evaluation versus digoxin. Author(s): Agostoni PG, Doria E, Berti M, Guazzi MD. Source: Clin Cardiol. 1994 October; 17(10): 536-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8001300

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Low-dose digoxin in patients with heart failure. Less toxic and at least as effective? Author(s): van Veldhuisen DJ. Source: Journal of the American College of Cardiology. 2002 March 20; 39(6): 954-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11897435

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Lower serum digoxin concentrations in heart failure and reassessment of laboratory report forms. Author(s): Sameri RM, Soberman JE, Finch CK, Self TH. Source: The American Journal of the Medical Sciences. 2002 July; 324(1): 10-3. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12120820

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Magnesium reversal of digoxin-facilitated ventricular rate during atrial fibrillation in the Wolff-Parkinson-White syndrome. Author(s): Merrill JJ, DeWeese G, Wharton JM. Source: The American Journal of Medicine. 1994 July; 97(1): 25-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8030653

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Magnesium sulfate in the treatment of ventricular arrhythmias due to digoxin toxicity. Author(s): Kinlay S, Buckley NA. Source: Journal of Toxicology. Clinical Toxicology. 1995; 33(1): 55-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7837314

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Malabsorption of digoxin tablets, gel caps, and elixir in a patient with an end jejunostomy. Author(s): Ehrenpreis ED, Guerriero S, Nogueras JJ, Carroll MA. Source: The Annals of Pharmacotherapy. 1994 November; 28(11): 1239-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7849335

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MDR1 genotype-related duodenal absorption rate of digoxin in healthy Japanese subjects. Author(s): Morita Y, Sakaeda T, Horinouchi M, Nakamura T, Kuroda K, Miki I, Yoshimura K, Sakai T, Shirasaka D, Tamura T, Aoyama N, Kasuga M, Okumura K. Source: Pharmaceutical Research. 2003 April; 20(4): 552-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12739761

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MDR1 genotype-related pharmacokinetics of digoxin after single oral administration in healthy Japanese subjects. Author(s): Sakaeda T, Nakamura T, Horinouchi M, Kakumoto M, Ohmoto N, Sakai T, Morita Y, Tamura T, Aoyama N, Hirai M, Kasuga M, Okumura K. Source: Pharmaceutical Research. 2001 October; 18(10): 1400-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11697464

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MDR1 genotypes do not influence the absorption of a single oral dose of 1 mg digoxin in healthy white males. Author(s): Gerloff T, Schaefer M, Johne A, Oselin K, Meisel C, Cascorbi I, Roots I. Source: British Journal of Clinical Pharmacology. 2002 December; 54(6): 610-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12492608

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MDR1-mediated interaction of digoxin with antiarrhythmic or antianginal drugs. Author(s): Kakumoto M, Takara K, Sakaeda T, Tanigawara Y, Kita T, Okumura K. Source: Biological & Pharmaceutical Bulletin. 2002 December; 25(12): 1604-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12499648

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Metabolism of digoxin and digoxigenin digitoxosides in rat liver microsomes: involvement of cytochrome P4503A. Author(s): Salphati L, Benet LZ. Source: Xenobiotica; the Fate of Foreign Compounds in Biological Systems. 1999 February; 29(2): 171-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10199593

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Microsampling homogeneous immunoassay with Cedia digoxin reagents on the Technicon CHEM 1 chemistry analyzer. Author(s): Lua AC, Chu DK, Vlastelica D. Source: Therapeutic Drug Monitoring. 1994 October; 16(5): 495-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7846748

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Mid- and long-term similarity of ventricular response to paroxysmal atrial fibrillation: digoxin versus placebo. Author(s): Hnatkova K, Murgatroyd FD, Poloniecki J, Waktare JE, Alferness CA, Camm AJ, Malik M. Source: Pacing and Clinical Electrophysiology : Pace. 1998 September; 21(9): 1735-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9744436

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Minimizing digoxin-like immunoreactivity with TDx digoxin in dialysis patients. Author(s): Martin-Suarez A, Calvo MV, Morales AI, Dominguez-Gil A. Source: Therapeutic Drug Monitoring. 1997 June; 19(3): 364-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9200781

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Mixed-effect modeling for detection and evaluation of drug interactions: digoxinquinidine and digoxin-verapamil combinations. Author(s): Bauer LA, Horn JR, Pettit H. Source: Therapeutic Drug Monitoring. 1996 February; 18(1): 46-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8848820

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Modulation of digoxin transport across Caco-2 cell monolayers by citrus fruit juices: lime, lemon, grapefruit, and pummelo. Author(s): Xu J, Go ML, Lim LY. Source: Pharmaceutical Research. 2003 February; 20(2): 169-76. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12636154

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Monitoring digoxin serum concentrations: new thoughts concerning an old drug. Author(s): Farver D. Source: S D J Med. 1999 May; 52(5): 161-2. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10358445

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Monitoring of unbound digoxin in patients treated with anti-digoxin antigen-binding fragments: a model for the future? Author(s): Valdes R Jr, Jortani SA. Source: Clinical Chemistry. 1998 September; 44(9): 1883-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9732971

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Multicenter study of Abbott AxSYM Digoxin II assay and comparison with 6 methods for susceptibility to digoxin-like immunoreactive factors. Author(s): Azzazy HM, Duh SH, Maturen A, Schaller E, Shaw L, Grimaldi R, Shock G, Christenson RH. Source: Clinical Chemistry. 1997 September; 43(9): 1635-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9299945

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Multilabeling of ferrocenes to a glucose oxidase-digoxin conjugate for the development of a homogeneous electroenzymatic immunoassay. Author(s): Suzawa T, Ikariyama Y, Aizawa M. Source: Analytical Chemistry. 1994 November 15; 66(22): 3889-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7810897

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Myocardial Na,K-ATPase and digoxin therapy in human heart failure. Author(s): Kjeldsen K, Bundgaard H. Source: Annals of the New York Academy of Sciences. 2003 April; 986: 702-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12763921

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Myocardial Na,K-ATPase: the molecular basis for the hemodynamic effect of digoxin therapy in congestive heart failure. Author(s): Kjeldsen K, Norgaard A, Gheorghiade M. Source: Cardiovascular Research. 2002 September; 55(4): 710-3. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12176120

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Natriuretic effect of digoxin-like immunoreactive substance on dog kidney. Author(s): Ahmad S, Dennis MB Jr, Jensen WM, Chow JL, Kenny MA. Source: Clin Physiol Biochem. 1987; 5(1): 1-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3581651

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Near-fatal yew berry intoxication treated with external cardiac pacing and digoxinspecific FAB antibody fragments. Author(s): Cummins RO, Haulman J, Quan L, Graves JR, Peterson D, Horan S. Source: Annals of Emergency Medicine. 1990 January; 19(1): 38-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2297154

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Negative interference with the Du Pont aca method for measuring digoxin. Author(s): Kanan R, Chan KM, Dietzler DN. Source: Clinical Chemistry. 1987 March; 33(3): 446. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3815829

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Negative interference with the Du Pont aca method for measuring digoxin--a reply. Author(s): Crouse SP. Source: Clinical Chemistry. 1987 July; 33(7): 1303. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3594901

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Neurohumoral effects of digoxin: a target for further investigation. Author(s): Gheorghiade M. Source: Cardiologia. 1996 October; 41(10): 967-72. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8940784

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New method for obtaining large quantities of endogenous digoxin-like substance. Author(s): Shilo L, Solomon G, Shenkman L. Source: Clinical Chemistry. 1987 August; 33(8): 1470-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2440619

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Nicardipine does not significantly affect serum digoxin concentrations at the steady state of patients with congestive heart failure. Author(s): Debruyne D, Commeau P, Grollier G, Huret B, Scanu P, Moulin M. Source: Int J Clin Pharmacol Res. 1989; 9(1): 15-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2707921

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Nighttime dosing assures postdistribution sampling for therapeutic drug monitoring of digoxin. Author(s): Bernard DW, Bowman RL, Grimm FA, Wolf BA, Simson MB, Shaw LM. Source: Clinical Chemistry. 1996 January; 42(1): 45-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8565231

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Nisoldipine, a new calcium antagonist, elevates plasma levels of digoxin. Author(s): Kirch W, Stenzel J, Santos SR, Ohnhaus EE. Source: Arch Toxicol Suppl. 1987; 11: 310-2. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3477190

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No consensus yet on the benefits of digoxin. Author(s): Jolobe OM. Source: Br J Hosp Med. 1992 May 20-June 2; 47(10): 785. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1606468

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No consensus yet on the benefits of digoxin. Author(s): Davies MK. Source: Br J Hosp Med. 1992 May 20-June 2; 47(10): 785-6. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1472190

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No effect of probenecid on the renal and biliary clearances of digoxin in man. Author(s): Hedman A, Angelin B, Arvidsson A, Dahlqvist R. Source: British Journal of Clinical Pharmacology. 1991 July; 32(1): 63-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1888643

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No effect of rosuvastatin on the pharmacokinetics of digoxin in healthy volunteers. Author(s): Martin PD, Kemp J, Dane AL, Warwick MJ, Schneck DW. Source: Journal of Clinical Pharmacology. 2002 December; 42(12): 1352-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12463730

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No pharmacokinetic interaction between iloprost and digoxin. Author(s): Penin E, Cheymol G, Bouslama K, Benchouieb A, Cabane J, Souvignet G. Source: European Journal of Clinical Pharmacology. 1991; 41(5): 505-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1722169

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No significant in vitro interference of diltiazem and metabolites in digoxin radioimmunoassay (four assay methods). Author(s): Molin L, Scherling IL, Larsson H. Source: Therapeutic Drug Monitoring. 1989; 11(2): 217-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2718226

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Nonazotemic hyperkalemia with renal and extrarenal defects in potassium transport: association with high levels of digoxin-like immunoreactive factor. Author(s): Szylman P, Wolach B, Winaver J, Panett R, Cohen P, Shenkman L, Better OS. Source: The Journal of Laboratory and Clinical Medicine. 1990 September; 116(3): 315-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2205695

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Noncompetitive immunoassay of small analytes at the femtomolar level by affinity probe capillary electrophoresis: direct analysis of digoxin using a uniform-labeled scFv immunoreagent. Author(s): Hafner FT, Kautz RA, Iverson BL, Tim RC, Karger BL. Source: Analytical Chemistry. 2000 December 1; 72(23): 5779-86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11128936

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Non-pretreatment digoxin assays and developments in immunoanalyzers. Author(s): Armbruster DA. Source: Clin Lab Sci. 1997 March-April; 10(2): 87-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10166357

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Ocular adverse effects to the therapeutic administration of digoxin. Author(s): Hobley A, Lawrenson J. Source: Ophthalmic & Physiological Optics : the Journal of the British College of Ophthalmic Opticians (Optometrists). 1991 October; 11(4): 391-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1771077

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Optimal digoxin concentrations for patients with heart failure. Author(s): Carbonin P, Zuccala G. Source: Jama : the Journal of the American Medical Association. 2003 May 28; 289(20): 2643; Author Reply 2643-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12771104

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Optimal digoxin concentrations for patients with heart failure. Author(s): de Denus S, Spinler SA. Source: Jama : the Journal of the American Medical Association. 2003 May 28; 289(20): 2643; Author Reply 2643-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12771103

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Optimizing digoxin dosage: the long winding road. Author(s): Po AL, Kendall MJ. Source: Journal of Clinical Pharmacy and Therapeutics. 2003 October; 28(5): 347-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14632957

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Optimum dose of digoxin. Author(s): Behr ER, Veysey MJ, Berry D, Volans GN. Source: Lancet. 1997 June 21; 349(9068): 1845. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9269246

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Optimum dose of digoxin. Author(s): Zuccala G, Pedone C, Carosella L, Carbonin P, Bernabei R. Source: Lancet. 1997 June 21; 349(9068): 1845. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9269245

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Oral bioavailability of digoxin is enhanced by talinolol: evidence for involvement of intestinal P-glycoprotein. Author(s): Westphal K, Weinbrenner A, Giessmann T, Stuhr M, Franke G, Zschiesche M, Oertel R, Terhaag B, Kroemer HK, Siegmund W. Source: Clinical Pharmacology and Therapeutics. 2000 July; 68(1): 6-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10945310

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Oral salbutamol decreases serum digoxin concentration. Author(s): Edner M, Jogestrand T. Source: European Journal of Clinical Pharmacology. 1990; 38(2): 195-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2338119

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Organic anion transporter oatp2-mediated interaction between digoxin and amiodarone in the rat liver. Author(s): Kodawara T, Masuda S, Wakasugi H, Uwai Y, Futami T, Saito H, Abe T, Inu K. Source: Pharmaceutical Research. 2002 June; 19(6): 738-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12134942

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Oxygen administration increases plasma digoxin-like substance and renal sodium excretion in chronic hypoxic patients. Author(s): De Angelis C, Perrone A, Ferri C, Piccoli A, Bellini C, D'Amelio R, Santucci A, Balsano F. Source: American Journal of Nephrology. 1993; 13(3): 173-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8213927

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Permanently oriented antibody immobilization for digoxin determination with a flow-through fluoroimmunosensor. Author(s): Fernandez P, Durand JS, Perez-Conde C, Paniagua G. Source: Analytical and Bioanalytical Chemistry. 2003 April; 375(8): 1020-3. Epub 2003 February 28. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12733013

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P-glycoprotein as the mediator of itraconazole-digoxin interaction. Author(s): Angirasa AK, Koch AZ. Source: Journal of the American Podiatric Medical Association. 2002 September; 92(8): 471-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12237270

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P-glycoprotein-mediated intestinal and biliary digoxin transport in humans. Author(s): Drescher S, Glaeser H, Murdter T, Hitzl M, Eichelbaum M, Fromm MF. Source: Clinical Pharmacology and Therapeutics. 2003 March; 73(3): 223-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12621387

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Pharmacoepidemiologic detection of calcium channel blocker-induced change on digoxin clearance using multiple trough screen analysis. Author(s): Suematsu F, Yukawa E, Yukawa M, Minemoto M, Ohdo S, Higuchi S, Goto Y. Source: Biopharmaceutics & Drug Disposition. 2002 July; 23(5): 173-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12116048

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Pharmacokinetic and pharmaceutic interaction between digoxin and Cremophor RH40. Author(s): Tayrouz Y, Ding R, Burhenne J, Riedel KD, Weiss J, Hoppe-Tichy T, Haefeli WE, Mikus G. Source: Clinical Pharmacology and Therapeutics. 2003 May; 73(5): 397-405. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12732840

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Population pharmacokinetics of digoxin in Egyptian pediatric patients: impact of one data point utilization. Author(s): EL Desoky ES, Nagaraja NV, Derendorf H. Source: American Journal of Therapeutics. 2002 November-December; 9(6): 492-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12424506

Studies

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Population pharmacokinetics of digoxin in Japanese patients: a 2-compartment pharmacokinetic model. Author(s): Yukawa E, Suematu F, Yukawa M, Minemoto M, Ohdo S, Higuchi S, Goto Y, Aoyama T. Source: Clinical Pharmacokinetics. 2001; 40(10): 773-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11707062

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Population pharmacokinetics of digoxin in pediatric patients. Author(s): Martin-Suarez A, Falcao AC, Outeda M, Hernandez FJ, Gonzalez MC, Quero M, Arranz I, Lanao JM. Source: Therapeutic Drug Monitoring. 2002 December; 24(6): 742-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12451291

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Predictive performance of serum digoxin concentration in patients with congestive heart failure by a hyperbolic model based on creatinine clearance. Author(s): Konishi H, Shimizu S, Chiba M, Minouchi T, Koida M, Yamaji A. Source: Journal of Clinical Pharmacy and Therapeutics. 2002 August; 27(4): 257-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12174027

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Quality control practices for calcium, cholesterol, digoxin, and hemoglobin: a College of American Pathologists Q-probes study in 505 hospital laboratories. Author(s): Steindel SJ, Tetrault G. Source: Archives of Pathology & Laboratory Medicine. 1998 May; 122(5): 401-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9593339

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Quantifying non-compliance in patients receiving digoxin--a pharmacokinetic approach. Author(s): Wiseman IC, Miller R. Source: South African Medical Journal. Suid-Afrikaanse Tydskrif Vir Geneeskunde. 1991 February 2; 79(3): 155-7. Erratum In: S Afr Med J 1991 March 2; 79(5): 286. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1994486

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Quantitation of interference in digoxin immunoassay in renal, hepatic, and diabetic disease. Author(s): Tzou MC, Reuning RH, Sams RA. Source: Clinical Pharmacology and Therapeutics. 1997 April; 61(4): 429-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9129560

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Quinidine reduces biliary clearance of digoxin in man. Author(s): Angelin B, Arvidsson A, Dahlqvist R, Hedman A, Schenck-Gustafsson K. Source: European Journal of Clinical Investigation. 1987 June; 17(3): 262-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3113970

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Quinidine-digoxin interaction: are the pharmacokinetics of both drugs altered? Author(s): Rameis H. Source: Int J Clin Pharmacol Ther Toxicol. 1985 March; 23(3): 145-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3997300

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Rapid loading of sotalol or amiodarone for management of recent onset symptomatic atrial fibrillation: a randomized, digoxin-controlled trial. Author(s): Thomas SP, Guy D, Wallace E, Crampton R, Kijvanit P, Eipper V, Ross DL, Cooper MJ. Source: American Heart Journal. 2004 January; 147(1): E3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14691441

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Recommended therapeutic digoxin blood levels: a cause for concern. Author(s): Woollard KV. Source: The Medical Journal of Australia. 2003 September 15; 179(6): 328. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12964923

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Re-entrant supraventricular tachycardia in infancy: current role of prophylactic digoxin treatment. Author(s): Pfammatter JP, Stocker FP. Source: European Journal of Pediatrics. 1998 February; 157(2): 101-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9504781

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Removal of digoxin and doxorubicin by multidrug resistance protein-overexpressed cell culture in hollow fiber. Author(s): Tsuruoka S, Sugimoto KI, Ueda K, Suzuki M, Imai M, Fujimura A. Source: Kidney International. 1999 July; 56(1): 154-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10411688

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Removal of digoxin by column for specific adsorption of beta(2)-microglobulin: a potential use for digoxin intoxication. Author(s): Tsuruoka S, Osono E, Nishiki K, Kawaguchi A, Arai T, Furuyoshi S, Saito T, Takata S, Sugimoto K, Kurihara S, Fujimura A. Source: Clinical Pharmacology and Therapeutics. 2001 June; 69(6): 422-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11406739

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Repeated administration of the novel antiepileptic agent levetiracetam does not alter digoxin pharmacokinetics and pharmacodynamics in healthy volunteers. Author(s): Levy RH, Ragueneau-Majlessi I, Baltes E. Source: Epilepsy Research. 2001 August; 46(2): 93-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11463510

Studies

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Report of a suicidal digoxin intoxication: a case report. Author(s): Rodriguez-Calvo MS, Rico R, Lopez-Rivadulla M, Suarez-Penaranda JM, Munoz JI, Concheiro L. Source: Med Sci Law. 2002 July; 42(3): 265-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12201074

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Rising digoxin serum levels and intoxication despite digoxin withdrawal in an elderly patient: a case report. Author(s): Peeters P, Vandergoten P, Lambert M, Mets T. Source: Acta Clin Belg. 2002 September-October; 57(5): 250-3. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12534131

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Role of human MDR1 gene polymorphism in bioavailability and interaction of digoxin, a substrate of P-glycoprotein. Author(s): Kurata Y, Ieiri I, Kimura M, Morita T, Irie S, Urae A, Ohdo S, Ohtani H, Sawada Y, Higuchi S, Otsubo K. Source: Clinical Pharmacology and Therapeutics. 2002 August; 72(2): 209-19. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12189368

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Rosiglitazone does not affect the steady-state pharmacokinetics of digoxin. Author(s): Di Cicco RA, Miller AK, Patterson S, Freed MI. Source: Journal of Clinical Pharmacology. 2000 December; 40(12 Pt 2): 1516-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11185675

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Safety concerns about digoxin after acute myocardial infarction. Author(s): Spargias KS, Hall AS, Ball SG. Source: Lancet. 1999 July 31; 354(9176): 391-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10437870

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Serum and tissue glycoconjugates, digoxin and magnesium levels in chronic calcific pancreatitis. Author(s): Kumar RA, Kurup PA. Source: Indian J Gastroenterol. 2001 November-December; 20(6): 230-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11817776

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Serum cystatin C is not a better marker of creatinine or digoxin clearance than serum creatinine. Author(s): O'Riordan S, Ouldred E, Brice S, Jackson SH, Swift CG. Source: British Journal of Clinical Pharmacology. 2002 April; 53(4): 398-402. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11966673

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Serum itraconazole and hydroxyitraconazole concentrations and interaction with digoxin in a case of chronic hypertrophic pachymenigitis caused by Aspergillus flavus. Author(s): Mochizuki M, Murase S, Takahashi K, Shimada S, Kume H, Iizuka T, Fukuda M. Source: Nihon Ishinkin Gakkai Zasshi = Japanese Journal of Medical Mycology. 2000; 41(1): 33-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10660641

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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/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11210401

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Sex-based differences in the effect of digoxin for the treatment of heart failure. Author(s): Rathore SS, Wang Y, Krumholz HM. Source: The New England Journal of Medicine. 2002 October 31; 347(18): 1403-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12409542

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Significant genetic linkage of MDR1 polymorphisms at positions 3435 and 2677: functional relevance to pharmacokinetics of digoxin. Author(s): Horinouchi M, Sakaeda T, Nakamura T, Morita Y, Tamura T, Aoyama N, Kasuga M, Okumura K. Source: Pharmaceutical Research. 2002 October; 19(10): 1581-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12425480

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Successful digoxin therapy of fetal supraventricular tachycardia in a triplet pregnancy. Author(s): Jones LM, Garmel SH. Source: Obstetrics and Gynecology. 2001 November; 98(5 Pt 2): 921-3. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11704204

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Successful treatment of digoxin intoxication by haemoperfusion with specific columns for beta2-microgloblin-adsorption (Lixelle) in a maintenance haemodialysis patient. Author(s): Kaneko T, Kudo M, Okumura T, Kasiwagi T, Turuoka S, Simizu M, Iino Y, Katayama Y. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2001 January; 16(1): 195-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11209033

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Suppression of total digoxin concentrations by digoxin-like immunoreactive substances in the MEIA digoxin assay. Elimination of negative interference by monitoring free digoxin concentrations. Author(s): Dasgupta A, Trejo O. Source: American Journal of Clinical Pathology. 1999 March; 111(3): 406-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10078117

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Teriparatide has no effect on the calcium-mediated pharmacodynamics of digoxin. Author(s): Benson CT, Voelker JR. Source: Clinical Pharmacology and Therapeutics. 2003 January; 73(1): 87-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12545147

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The effect of digoxin on the electrocardiogram of healthy middle-aged and elderly patients at rest and during exercise--a comparison with the ECG reaction induced by myocardial ischemia. Author(s): Sundqvist K, Jogestrand T, Nowak J. Source: Journal of Electrocardiology. 2002 July; 35(3): 213-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12122611

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The effect of digoxin on the quality of life in patients with heart failure. Author(s): Lader E, Egan D, Hunsberger S, Garg R, Czajkowski S, McSherry F. Source: Journal of Cardiac Failure. 2003 February; 9(1): 4-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12612867

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The effect of erythromycin and clarithromycin on the pharmacokinetics of intravenous digoxin in healthy volunteers. Author(s): Tsutsumi K, Kotegawa T, Kuranari M, Otani Y, Morimoto T, Matsuki S, Nakano S. Source: Journal of Clinical Pharmacology. 2002 October; 42(10): 1159-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12362931

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The effects of captopril on serum digoxin levels in patients with severe congestive heart failure. Author(s): Kirimli O, Kalkan S, Guneri S, Tuncok Y, Akdeniz B, Ozdamar M, Guven H. Source: Int J Clin Pharmacol Ther. 2001 July; 39(7): 311-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11471775

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The effects of enalapril-digoxin-diuretic combination therapy on nutritional and anthropometric indices in chronic congestive heart failure: preliminary findings in cardiac cachexia. Author(s): Adigun AQ, Ajayi AA. Source: European Journal of Heart Failure : Journal of the Working Group on Heart Failure of the European Society of Cardiology. 2001 June; 3(3): 359-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11378008

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The effects of tegaserod (HTF 919) on the pharmacokinetics and pharmacodynamics of digoxin in healthy subjects. Author(s): Zhou H, Horowitz A, Ledford PC, Hubert M, Appel-Dingemanse S, Osborne S, McLeod JF. Source: Journal of Clinical Pharmacology. 2001 October; 41(10): 1131-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11583482

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The practice of digoxin therapeutic drug monitoring. Author(s): Barclay M, Begg E. Source: N Z Med J. 2003 December 12; 116(1187): U704. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14752532

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Therapeutic monitoring of digoxin and antiepileptic drugs in Egypt and Saudi Arabia. Author(s): EL Desoky ES, AL-Ghamdi HA, Halaby FH, Al-Beshri M. Source: Therapeutic Drug Monitoring. 2003 April; 25(2): 211-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12657916

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Toad venom poisoning: resemblance to digoxin toxicity and therapeutic implications. Author(s): Gowda RM, Cohen RA, Khan IA. Source: Heart (British Cardiac Society). 2003 April; 89(4): E14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12639891

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Understanding digoxin use in the elderly patient. Author(s): Tsang P, Gerson B. Source: Clin Lab Med. 1990 September; 10(3): 479-92. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2253445

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Undiagnosed hypothyroidism: a risk factor for digoxin toxicity. Author(s): Shapiro VW, Podrazik P. Source: The American Journal of Emergency Medicine. 1993 November; 11(6): 670-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8240577

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Unexpected suppression of total digoxin concentrations by cross-reactants in the microparticle enzyme immunoassay: elimination of interference by monitoring free digoxin concentration. Author(s): Dasgupta A, Scott J. Source: American Journal of Clinical Pathology. 1998 July; 110(1): 78-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9661925

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Unexplained increase in serum digoxin: a case report. Author(s): Doolittle MH, Lincoln K, Graves SW. Source: Clinical Chemistry. 1994 March; 40(3): 487-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8131287

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Update on digoxin and other oral positive inotropic agents for chronic heart failure. Author(s): Reddy S, Benatar D, Gheorghiade M. Source: Current Opinion in Cardiology. 1997 May; 12(3): 233-41. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9243080

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Use of digoxin Fab immune fragments in a seven-day-old infant. Author(s): Kaufman J, Leikin J, Kendzierski D, Polin K. Source: Pediatric Emergency Care. 1990 June; 6(2): 118-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2371148

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Use of digoxin in diastolic heart failure. Author(s): Dhir SK. Source: The Journal of Laboratory and Clinical Medicine. 2001 October; 138(4): 277. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11574822

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Use of digoxin in heart failure. Should we bother? Author(s): Frank J, Evans MF. Source: Can Fam Physician. 1997 July; 43: 1227-8. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9241459

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Use of digoxin in patients with sinus rhythm and heart failure. Author(s): Zatuchni J. Source: Dicp. 1990 December; 24(12): 1232. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2089837

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Use of digoxin, diuretics, beta blockers, angiotensin-converting enzyme inhibitors, and calcium channel blockers in older patients in an academic hospital-based geriatrics practice. Author(s): Fishkind D, Paris BE, Aronow WS. Source: Journal of the American Geriatrics Society. 1997 July; 45(7): 809-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9215330

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Validity of unbound digoxin measurements by immunoassays in presence of antidote (Digibind). Author(s): Jortani SA, Pinar A, Johnson NA, Valdes R Jr. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 1999 May; 283(1-2): 159-69. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10404740

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Value of digoxin in heart failure and sinus rhythm: new features of an old drug? Author(s): van Veldhuisen DJ, de Graeff PA, Remme WJ, Lie KI. Source: Journal of the American College of Cardiology. 1996 October; 28(4): 813-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8837553

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Variation in apparent serum digitalis-like factor levels with different digoxin antibodies. The "immunochemical fingerprint". Author(s): Naomi S, Graves S, Lazarus M, Williams GH, Hollenberg NK. Source: American Journal of Hypertension : Journal of the American Society of Hypertension. 1991 October; 4(10 Pt 1): 795-801. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1747212

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Vasodilators as first-line therapy for congestive heart failure: a comparative hemodynamic study of hydralazine, digoxin, and their combination. Author(s): Ribner HS, Zucker MJ, Stasior C, Talentowski D, Stadnicki R, Lesch M. Source: American Heart Journal. 1987 July; 114(1 Pt 1): 91-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3604877

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Ventricular fibrillation following adenosine therapy for supraventricular tachycardia in a neonate with concealed Wolff-Parkinson-White syndrome treated with digoxin. Author(s): Mulla N, Karpawich PP. Source: Pediatric Emergency Care. 1995 August; 11(4): 238-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8532572

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Ventricular rate control in the elderly: is digoxin enough? Author(s): Falk RH. Source: The American Journal of Geriatric Cardiology. 2002 November-December; 11(6): 353-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12417840

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Verapamil-digoxin interaction in chronic hemodialysis patients. Author(s): Rendtorff C, Johannessen AC, Halck S, Klitgaard NA. Source: Scandinavian Journal of Urology and Nephrology. 1990; 24(2): 137-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2356453

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VERDICT: the Verapamil versus Digoxin Cardioversion Trial: A randomized study on the role of calcium lowering for maintenance of sinus rhythm after cardioversion of persistent atrial fibrillation. Author(s): Van Noord T, Van Gelder IC, Tieleman RG, Bosker HA, Tuinenburg AE, Volkers C, Veeger NJ, Crijns HJ. Source: Journal of Cardiovascular Electrophysiology. 2001 July; 12(7): 766-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11469424

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Vitros digoxin immunoassay evaluated for interference by digoxin-like immunoreactive factors. Author(s): Way BA, Wilhite TR, Miller R, Smith CH, Landt M. Source: Clinical Chemistry. 1998 June; 44(6 Pt 1): 1339-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9625062

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Voriconazole does not affect the steady-state pharmacokinetics of digoxin. Author(s): Purkins L, Wood N, Kleinermans D, Nichols D. Source: British Journal of Clinical Pharmacology. 2003 December; 56 Suppl 1: 45-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14616413

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When digoxin harms instead of helps. Author(s): Wallace CJ. Source: Rn. 1995 September; 58(9): 26-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7676206

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When should digoxin be used in patients with diastolic dysfunction? Author(s): Yamani MH. Source: Cleve Clin J Med. 2001 June; 68(6): 481, 485. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11405608

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When, and when not, to use digoxin in the elderly. Author(s): Gosselink AT, van Veldhuisen DJ, Crijns HJ. Source: Drugs & Aging. 1997 June; 10(6): 411-20. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9205847

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Which cardiac disturbances should be treated with digoxin immune Fab (ovine) antibody? Author(s): Marchlinski FE, Hook BG, Callans DJ. Source: The American Journal of Emergency Medicine. 1991 March; 9(2 Suppl 1): 24-8; Discussion 33-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1997018

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Withdrawal of digoxin from patients with chronic heart failure treated with angiotensin-converting-enzyme inhibitors. Author(s): Joffe I. Source: The New England Journal of Medicine. 1993 December 9; 329(24): 1820. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8232503

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Withdrawal of digoxin from patients with chronic heart failure treated with angiotensin-converting-enzyme inhibitors. Author(s): Devereux RB. Source: The New England Journal of Medicine. 1993 December 9; 329(24): 1820. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8232502

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Withdrawal of digoxin from patients with chronic heart failure treated with angiotensin-converting-enzyme inhibitors. Author(s): O'Mara NB, Zimmerman WB. Source: The New England Journal of Medicine. 1993 December 9; 329(24): 1819-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8232501

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Withdrawal of digoxin from patients with chronic heart failure treated with angiotensin-converting-enzyme inhibitors. RADIANCE Study. Author(s): Packer M, Gheorghiade M, Young JB, Costantini PJ, Adams KF, Cody RJ, Smith LK, Van Voorhees L, Gourley LA, Jolly MK. Source: The New England Journal of Medicine. 1993 July 1; 329(1): 1-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8505940

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Withdrawal of maintenance digoxin from institutionalized elderly. Author(s): Liddle BJ. Source: Postgraduate Medical Journal. 1991 June; 67(788): 588. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1924037

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Withdrawal of maintenance digoxin from institutionalized elderly. Author(s): Macarthur C. Source: Postgraduate Medical Journal. 1990 November; 66(781): 940-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2267207

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CHAPTER 2. NUTRITION AND DIGOXIN Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and digoxin.

Finding Nutrition Studies on Digoxin 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 “digoxin” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

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

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

Calcium and digoxin vs. calcium alone for severe verapamil toxicity. Author(s): Department of Emergency Medicine, the College of Physicians and Surgeons at Columbia University, St. Luke's-Roosevelt Hospital Center, New York, NY 10019, USA. [email protected] Source: Bania, T C Blaufeux, B Hughes, S Almond, G L Homel, P Acad-Emerg-Med. 2000 October; 7(10): 1089-96 1069-6563

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Cardiotoxicity studies on interaction of lead, digoxin & calcium. Source: Krishnamoorthy, M S Muthu, P Ahmed, M M Indian-J-Med-Res. 1987 December; 86792-6 0971-5916

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Clinical utility of plasma digoxin measurements. Author(s): 1st Medical Clinic, Institute of Medicine, Timisoara, Romania. Source: Cristodorescu, R Deutsch, G Dragan, S Med-Interne. 1989 Jan-March; 27(1): 2532 0377-1202

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Comparison of the digoxin marker with capsule counting and compliance questionnaire methods for measuring compliance to medication in a clinical trial. Author(s): Helsinki Heart Study, Finland. Source: Maenpaa, H Manninen, V Heinonen, O P Eur-Heart-J. 1987 October; 8 Suppl I3943 0195-668X

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Different effects of in vivo ouabain and digoxin on renal artery function and blood pressure in the rat. Author(s): Department of Physiology, School of Medicine, University of Maryland, Baltimore 21201, USA. Source: Kimura, K Manunta, P Hamilton, B P Hamlyn, J M Hypertens-Res. 2000 September; 23 SupplS67-76 0916-9636

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Digoxin-like immunoreactive substance in the elderly patient and its impact on the TDx digoxin assay. Author(s): Department of Preventive Medicine, Medical Research Institute, Tokyo Medical and Dental University, Japan. Source: Yamamoto, T Takano, K Sanaka, M Nomura, Y Koike, Y Mineshita, S TherDrug-Monit. 1998 August; 20(4): 417-21 0163-4356

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Effect of a Chinese medicine “kyushin” on serum digoxin concentration measurement in dogs. Author(s): Department of Internal Medicine, Chung Shan Medical and Dental College Hospital, Taiwan, Republic of China. Source: Lin, C S Lin, M C Chen, K S Liu, C B Jpn-Circ-J. 1989 February; 53(2): 108-12 0047-1828

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Effect of Chinese medicines Chan Su and Danshen on EMIT 2000 and Randox digoxin immunoassays: wide variation in digoxin-like immunoreactivity and magnitude of interference in digoxin measurement by different brands of the same product. Author(s): Bayer Diagnostics, Tarrytown, New York, USA. Source: Datta, P Dasgupta, A Ther-Drug-Monit. 2002 October; 24(5): 637-44 0163-4356

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Effect of ouabain, digoxin and digitoxigenin on potassium uptake and histamine release from rat peritoneal mast cells. Author(s): Department of Pharmacology, Odense University, Denmark.

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Source: Knudsen, T FerJanuary, I Johansen, T FEBS-Lett. 1993 April 26; 321(2-3): 127-31 0014-5793 •

Effect of PSC 833, a P-glycoprotein modulator, on the disposition of vincristine and digoxin in rats. Author(s): Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. Source: Song, S Suzuki, H Kawai, R Sugiyama, Y Drug-Metab-Dispos. 1999 June; 27(6): 689-94 0090-9556

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Effect of quinidine on the hepatic uptake of digoxin in guinea pigs. Author(s): Faculty of Pharmaceutical Sciences, University of Tokyo, Japan. Source: Okudaira, K Sawada, Y Sugiyama, Y Iga, T Hanano, M J-Pharmacobiodyn. 1989 January; 12(1): 24-30 0386-846X

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Effects of AN-132 and quinidine, antiarrhythmic agents, on plasma digoxin concentrations in rats. Author(s): Department of Pharmacology, Chugai Pharmaceutical Co., Ltd., Japan. Source: Sakai, K Yamazaki, T Hinohara, Y J-Pharm-Pharmacol. 1988 January; 40(1): 68-9 0022-3573

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Effects of nicorandil and verapamil, antianginal agents, on plasma digoxin concentrations in rats and dogs. Source: Hinohara, Y Yamazaki, T Kuromaru, O Homma, N Sakai, K J-Pharm-Pharmacol. 1987 July; 39(7): 512-6 0022-3573

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Familial hypodigoxinemic membrane Na(+)-K(+) ATPase upregulatory syndrome relation between digoxin status and cerebral dominance. Author(s): Department of Neurology, Medical College Hospital, Trivandrum, Kerala, India. Source: KuMarch, A R Kurup, P A Neurol-India. 2002 September; 50(3): 340-7 0028-3886

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Growth and digoxin content in Digitalis lanata in controlled conditions and natural environment. Source: Brugidou, C Jacques, M Cosson, L Jarreau, F X Ogerau, T Planta-Med. 1988 June; 54(3): 262-5 0032-0943

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Influence of wheat bran and of a bulk-forming ispaghula cathartic on the bioavailability of digoxin in geriatric in-patients. Source: Nordstrom, M Melander, A Robertsson, E Steen, B Drug-Nutr-Interact. 1987; 5(2): 67-9 0272-3530

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Inhibition by basic drugs of digoxin secretion into human bile. Author(s): Department of Clinical Pharmacology, Karolinska Institute, Huddinge University Hospital, Sweden. Source: Hedman, A Eur-J-Clin-Pharmacol. 1992; 42(4): 457-9 0031-6970

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Interactions between drugs and Asian medicine: displacement of digitoxin from protein binding site by bufalin, the constituent of Chinese medicines Chan Su and Lu-Shen-Wan. Author(s): Bayer Diagnostics, E. Walpole, MA, USA. Source: Datta, P Dasgupta, A Ther-Drug-Monit. 2000 April; 22(2): 155-9 0163-4356

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Intravenous digoxin blunts the rise of inotropy induced by isometric exercise: a noninvasive study in healthy volunteers. Author(s): First Department of Medicine, University Central Hospital, Helsinki, Finland. Source: Partanen, J Pellinen, T Nieminen, M S Ann-Clin-Res. 1987; 19(6): 383-90 00034762

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Lack of effect of captopril on serum digoxin in congestive heart failure. Author(s): Institute of Cardiovascular Diseases, University of Bologna, Italy. Source: Magelli, C Bassein, L Ribani, M A Liberatore, S Ambrosioni, E Magnani, B Eur-JClin-Pharmacol. 1989; 36(1): 99-100 0031-6970

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Prescribing digoxin in geriatric units: the unexplained variability in dosage requirements. Author(s): Medicine for the Elderly, Barnet General Hospital, Hertfordshire. Source: Dobbs, R J Royston, J P O'Neill, C J Deshmukh, A A Nicholson, P W Denham, M J Dobbs, S M Eur-J-Clin-Pharmacol. 1987; 32(6): 611-4 0031-6970

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The effect of digoxin dosage on the digoxin-quinidine interaction in the bile ductcannulated rat. Source: Hewick, D S Ostenfeld, T J-Pharm-Pharmacol. 1987 January; 39(1): 64-7 00223573

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

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

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The following is a specific Web list relating to digoxin; 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 Thiamine Alternative names: Vitamin B1 (Thiamine) Source: Integrative Medicine Communications; www.drkoop.com Vitamin B1 (Thiamine) Alternative names: Thiamine Source: Integrative Medicine Communications; www.drkoop.com

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Minerals Calcium Source: Integrative Medicine Communications; www.drkoop.com Magnesium Source: Healthnotes, Inc.; www.healthnotes.com Magnesium Source: Integrative Medicine Communications; www.drkoop.com Magnesium Hydroxide Source: Healthnotes, Inc.; www.healthnotes.com Potassium Source: Healthnotes, Inc.; www.healthnotes.com Potassium Source: Integrative Medicine Communications; www.drkoop.com Potassium Chloride Source: Healthnotes, Inc.; www.healthnotes.com

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CHAPTER 3. ALTERNATIVE MEDICINE AND DIGOXIN Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to digoxin. 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 digoxin 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 “digoxin” (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 digoxin: •

12 beta-Hydroxylation of digitoxin by suspension-cultured Digitalis lanata cells: production of digoxin in 20-litre and 300-litre air-lift bioreactors. Author(s): Kreis W, Reinhard E. Source: Journal of Biotechnology. 1992 November; 26(2-3): 257-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1369154

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A digoxin-like immunoreactive substance and atrioventricular block induced by a Chinese medicine “kyushin”. Author(s): Lin CS, Lin MC, Chen KS, Ho CC, Tsai SR, Ho CS, Shieh WH. Source: Japanese Circulation Journal. 1989 September; 53(9): 1077-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2601000

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A fluorometric determination of myocardial digoxin at autopsy, with identification of digitalis leaf, digitoxin, and gitoxin. Author(s): Jelliffe RW, Stephenson RG.

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Source: American Journal of Clinical Pathology. 1969 March; 51(3): 347-57. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5765137 •

A model for the prediction of digoxin-drug interactions at the renal tubular cell level. Author(s): Woodland C, Ito S, Koren G. Source: Therapeutic Drug Monitoring. 1998 April; 20(2): 134-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9558126

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Acetyldigoxin and acetyldigitoxin from digitalis lanata. Author(s): Gisvold O. Source: Journal of Pharmaceutical Sciences. 1972 August; 61(8): 1320-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5050388

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Activated charcoal is more effective than equilibrium dialysis in removing Chinese medicines Chan Su and Dan Shen from serum and activated charcoal also prevents further absorption of these agents from G.I. tract in mice: monitoring the effect in clinical laboratory by measuring digoxin activity in serum. Author(s): Dasgupta A, Wahed A, Culton L, Olsen M, Wells A, Actor JK. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 2002 October; 324(1-2): 51-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12204425

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Acute pediatric digoxin ingestion. Author(s): Gittelman MA, Stephan M, Perry H. Source: Pediatric Emergency Care. 1999 October; 15(5): 359-62. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10532672

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Application of high-performance liquid chromatography to the separation of cardenolides and the assay of digoxin in Digitalis lanata leaf. Author(s): Cobb PH. Source: The Analyst. 1976 October; 101(1207): 768-76. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=984421

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Beneficial effect of digoxin-specific Fab antibody fragments in oleander intoxication. Author(s): Safadi R, Levy I, Amitai Y, Caraco Y. Source: Archives of Internal Medicine. 1995 October 23; 155(19): 2121-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7575073

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Bufalin and unidentified substance(s) in traditional Chinese medicine cross-react in commercial digoxin assay. Author(s): Panesar NS.

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Source: Clinical Chemistry. 1992 October; 38(10): 2155-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1395015 •

Central role of hypothalamic digoxin in conscious perception, neuroimmunoendocrine integration, and coordination of cellular function: relation to hemispheric dominance. Author(s): Kurup RK, Kurup PA. Source: The International Journal of Neuroscience. 2002 June; 112(6): 705-39. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12325312

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Chinese medicine interfering with digoxin immunoassays. Author(s): Fushimi R, Tachi J, Amino N, Miyai K. Source: Lancet. 1989 February 11; 1(8633): 339. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2563502

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Circulatory effects of disodium edetate in digoxin-induced ventricular tachycardia. Author(s): Pavek K, Drimal J, Selecky FV. Source: Cardiology. 1967; 50(5): 297-304. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4965975

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Clinical study on chronopharmacokinetics of digoxin in patients with congestive heart failure. Author(s): Liu Z, Fang S, Wang L, Zhu T, Yang H, Yu S. Source: J Tongji Med Univ. 1998; 18(1): 21-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10806796

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Cost-effectiveness analysis of the use of digoxin immune Fab (ovine) for treatment of digoxin toxicity. Author(s): Mauskopf JA, Wenger TL. Source: The American Journal of Cardiology. 1991 December 15; 68(17): 1709-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1746476

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Current considerations in digoxin usage. Author(s): Shapiro W. Source: Crc Crit Rev Clin Lab Sci. 1978; 9(4): 321-46. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=401374

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Digoxin 1785-1985. I. Two hundred years of digitalis. Author(s): Wade OL. Source: J Clin Hosp Pharm. 1986 February; 11(1): 3-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3514682

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Digoxin immunoassay and Chinese medicine. Author(s): Fushimi R, Amino N. Source: Clinical Chemistry. 1993 October; 39(10): 2203-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8280235

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Digoxin immunoassay that avoids cross-reactivity from Chinese medicines. Author(s): Fushimi R, Yamanishi H, Inoue M, Iyama S, Amino N. Source: Clinical Chemistry. 1995 April; 41(4): 621. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7720257

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Digoxin interaction with bran and high fiber foods. Author(s): Floyd RA. Source: Am J Hosp Pharm. 1978 June; 35(6): 660. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=665675

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Digoxin radioimmunoassay: sephadex separation of free from antibody-bound digoxin. Author(s): Bundgaard Christiansen NJ, Damkjaer Nielsen M. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 1972 November; 42(1): 125-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4654848

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Digoxin toxicity and electrolytes: a correlative study. Author(s): Sundar S, Burma DP, Vaish SK. Source: Acta Cardiol. 1983; 38(2): 115-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6603084

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Digoxin toxicity in a 26-year-old woman taking a herbal dietary supplement. Author(s): Scheinost ME. Source: J Am Osteopath Assoc. 2001 August; 101(8): 444-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11526877

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Digoxin type toxicity from ingestion of Thevetia peruvila or the case of the betel nut that wasn't. Author(s): Vince JD, Salamon B, Tau G, Zilibowicz M. Source: P N G Med J. 1984 September-December; 27(3-4): 167-9. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6598939

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Digoxin up-regulates MDR1 in human colon carcinoma Caco-2 cells. Author(s): Takara K, Tsujimoto M, Ohnishi N, Yokoyama T.

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Source: Biochemical and Biophysical Research Communications. 2002 March 22; 292(1): 190-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11890691 •

Digoxin-like factors in herbal teas. Author(s): Longerich L, Johnson E, Gault MH. Source: Clinical and Investigative Medicine. Medecine Clinique Et Experimentale. 1993 June; 16(3): 210-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8395986

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Digoxin-like immunoreactive factor in rat plasma: effect of sodium and calcium intake. Author(s): Doris PA. Source: Life Sciences. 1988; 42(7): 783-90. Erratum In: Life Sci 1988; 43(6): 569. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2828804

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Digoxin-like immunoreactivity in Chinese medicine. Author(s): Fushimi R, Koh T, Iyama S, Yasuhara M, Tachi J, Kohda K, Amino N, Miyai K. Source: Therapeutic Drug Monitoring. 1990 May; 12(3): 242-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2349606

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Digoxin-specific Fab fragments in the treatment of oleander toxicity in a canine model. Author(s): Clark RF, Selden BS, Curry SC. Source: Annals of Emergency Medicine. 1991 October; 20(10): 1073-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1928877

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Distribution and excretion of -acetyldigoxin following intravenous administration to the dog. Author(s): Kraupp O. Source: Planta Medica. 1971; : Suppl 4: 91-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5154919

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Drugs for atrial fibrillation. Digoxin comes from Digitalis lanata. Author(s): Hollman A. Source: Bmj (Clinical Research Ed.). 1996 April 6; 312(7035): 912. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8611904

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Effect of a Chinese medicine “kyushin” on serum digoxin concentration measurement in dogs. Author(s): Lin CS, Lin MC, Chen KS, Liu CB.

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Source: Japanese Circulation Journal. 1989 February; 53(2): 108-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2716172 •

Effect of administration of activated charcoal and fibre on absorption, excretion and steady state blood levels of digoxin and digitoxin. Evidence for intestinal secretion of the glycosides. Author(s): Reissell P, Manninen V. Source: Acta Med Scand Suppl. 1982; 668: 88-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6963097

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Effect of antioxidants (digoxin, quercetin, and ascorbic acid) on catalytic properties of horseradish peroxidase. Author(s): Rogozhin VV, Verkhoturov VV. Source: Biochemistry. Biokhimiia. 1998 June; 63(6): 657-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9668205

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Effect of Asian and Siberian ginseng on serum digoxin measurement by five digoxin immunoassays. Significant variation in digoxin-like immunoreactivity among commercial ginsengs. Author(s): Dasgupta A, Wu S, Actor J, Olsen M, Wells A, Datta P. Source: American Journal of Clinical Pathology. 2003 February; 119(2): 298-303. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12580002

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Effect of caffeine on the lethal dose of digoxin in dogs. Author(s): Scriabine A, Bellet S. Source: Toxicology and Applied Pharmacology. 1967 July; 11(1): 199-201. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6056152

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Effect of Chinese medicines Chan Su and Danshen on EMIT 2000 and Randox digoxin immunoassays: wide variation in digoxin-like immunoreactivity and magnitude of interference in digoxin measurement by different brands of the same product. Author(s): Datta P, Dasgupta A. Source: Therapeutic Drug Monitoring. 2002 October; 24(5): 637-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12352936

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Effect of PSC 833, a P-glycoprotein modulator, on the disposition of vincristine and digoxin in rats. Author(s): Song S, Suzuki H, Kawai R, Sugiyama Y. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 1999 June; 27(6): 689-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10348798

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Effect of St John's wort dose and preparations on the pharmacokinetics of digoxin. Author(s): Mueller SC, Uehleke B, Woehling H, Petzsch M, Majcher-Peszynska J, Hehl EM, Sievers H, Frank B, Riethling AK, Drewelow B. Source: Clinical Pharmacology and Therapeutics. 2004 June; 75(6): 546-57. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15179409

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Effect of the flavonoids biochanin A and silymarin on the P-glycoprotein-mediated transport of digoxin and vinblastine in human intestinal Caco-2 cells. Author(s): Zhang S, Morris ME. Source: Pharmaceutical Research. 2003 August; 20(8): 1184-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12948016

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Effect of the traditional Chinese medicines Chan Su, Lu-Shen-Wan, Dan Shen, and Asian ginseng on serum digoxin measurement by Tina-quant (Roche) and Synchron LX system (Beckman) digoxin immunoassays. Author(s): Chow L, Johnson M, Wells A, Dasgupta A. Source: Journal of Clinical Laboratory Analysis. 2003; 17(1): 22-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12526019

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Efficacy of digoxin specific Fab fragments (Digibind) in the treatment of toad venom poisoning. Author(s): Brubacher JR, Lachmanen D, Ravikumar PR, Hoffman RS. Source: Toxicon : Official Journal of the International Society on Toxinology. 1999 June; 37(6): 931-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10340832

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Elevated serum digoxin levels in a patient taking digoxin and Siberian ginseng. Author(s): McRae S. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 1996 August 1; 155(3): 293-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8705908

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Endogenous and exogenous digoxin-like immunoreactive substances: impact on therapeutic drug monitoring of digoxin. Author(s): Dasgupta A. Source: American Journal of Clinical Pathology. 2002 July; 118(1): 132-40. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12109847

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Evidence for a non-MDR1 component in digoxin secretion by human intestinal Caco2 epithelial layers. Author(s): Lowes S, Cavet ME, Simmons NL.

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Source: European Journal of Pharmacology. 2003 January 1; 458(1-2): 49-56. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12498906 •

Extraction and quantitation of digoxin and acetyldigoxin from the Digitalis lanata leaf via near-supercritical methanol-modified carbon dioxide. Author(s): Moore WN, Taylor LT. Source: Journal of Natural Products. 1996 July; 59(7): 690-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8759168

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Fab fragments in the treatment of digoxin overdose: pediatric considerations. Author(s): Fazio A. Source: Southern Medical Journal. 1987 December; 80(12): 1553-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2892273

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Factors of importance for valid digitalis assays particularly for the determination of digoxin in plasma and urine. Author(s): Molin L. Source: Acta Pharmacol Toxicol (Copenh). 1986; 59 Suppl 4: 1-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3739734

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Familial hypodigoxinemic membrane Na(+)-K(+) ATPase upregulatory syndrome relation between digoxin status and cerebral dominance. Author(s): Kumar AR, Kurup PA. Source: Neurology India. 2002 September; 50(3): 340-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12391467

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Familial hypothalamic digoxin deficiency syndrome. Author(s): Kurup RK, Kurup PA. Source: The Journal of Neuropsychiatry and Clinical Neurosciences. 2004 Winter; 16(1): 93-101. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14990764

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Fetal supraventricular tachycardia: in utero therapy with digoxin and quinidine. Author(s): Spinnato JA, Shaver DC, Flinn GS, Sibai BM, Watson DL, Marin-Garcia J. Source: Obstetrics and Gynecology. 1984 November; 64(5): 730-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6493666

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From bench to bedside: utilization of an in vitro model to predict potential drug-drug interactions in the kidney: the digoxin-mifepristone example. Author(s): Woodland C, Koren G, Ito S.

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Source: Journal of Clinical Pharmacology. 2003 July; 43(7): 743-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12856388 •

Growth and digoxin content in Digitalis lanata in controlled conditions and natural environment. Author(s): Brugidou C, Jacques M, Cosson L, Jarreau FX, Ogerau T. Source: Planta Medica. 1988 June; 54(3): 262-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3174863

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High-performance liquid chromatographic determination of alpha-acetyldigoxin in Digitalis lanata leaves. Author(s): Ikeda Y, Fujii Y, Yamazaki M. Source: Analytical Biochemistry. 1991 August 1; 196(2): 451-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1776696

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Human placental transport of vinblastine, vincristine, digoxin and progesterone: contribution of P-glycoprotein. Author(s): Ushigome F, Takanaga H, Matsuo H, Yanai S, Tsukimori K, Nakano H, Uchiumi T, Nakamura T, Kuwano M, Ohtani H, Sawada Y. Source: European Journal of Pharmacology. 2000 November 10; 408(1): 1-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11070177

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Hypothalamic digoxin, cerebral dominance, and mitochondrial function/free radical metabolism. Author(s): Kurup RK, Kurup PA. Source: The International Journal of Neuroscience. 2002 December; 112(12): 1409-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12652894

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Hypothalamic digoxin, hemispheric chemical dominance, and spirituality. Author(s): Kurup RK, Kurup PA. Source: The International Journal of Neuroscience. 2003 March; 113(3): 383-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12803140

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Hypothalamic digoxin, hemispheric chemical dominance, and the tridosha theory. Author(s): Kurup RK, Kurup PA. Source: The International Journal of Neuroscience. 2003 May; 113(5): 657-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12745626

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Hypothalamic digoxin--central role in conscious perception, neuroimmunoendocrine integration and coordination of cellular function--relation to hemispheric dominance. Author(s): Kurup RK, Kurup PA.

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Source: Medical Hypotheses. 2003 February; 60(2): 243-57. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12606243 •

Impact of ginkgo biloba on the pharmacokinetics of digoxin. Author(s): Mauro VF, Mauro LS, Kleshinski JF, Khuder SA, Wang Y, Erhardt PW. Source: American Journal of Therapeutics. 2003 July-August; 10(4): 247-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12845387

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Impaired protein binding of Chinese medicine DanShen in uremic sera and sera with hyperbilirubinemia: rapid assessment of total and free DanShen concentrations using the fluorescence polarization immunoassay for digoxin. Author(s): Wahed A, Pollard J, Wells A, Dasgupta A. Source: Journal of Clinical Laboratory Analysis. 2003; 17(5): 179-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12938147

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Improvements to the SYVA fluorescence energy transfer immunoassay for digoxin. Author(s): Lehmann DR. Source: Clinical Biochemistry. 1985 October; 18(5): 300-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3902286

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In vivo digoxin-like immunoreactivity in mice and interference of Chinese medicine Danshen in serum digoxin measurement: elimination of interference by using a chemiluminescent assay. Author(s): Dasgupta A, Actor JK, Olsen M, Wells A, Datta P. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 2002 March; 317(1-2): 231-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11814480

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Influence of kaolin--pectin suspension on digoxin bioavailability. Author(s): Albert KS, Ayres JW, DiSanto AR, Weidler DJ, Sakmar E, Hallmark MR, Stoll RG, DeSante KA, Wagner JG. Source: Journal of Pharmaceutical Sciences. 1978 November; 67(11): 1582-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=712596

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Influence of potassium depletion on myocardial concentration of tritiated digoxin. Author(s): Cohn KE, Kleiger RE, Harrison DC. Source: Circulation Research. 1967 May; 20(5): 473-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6057680

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Influence of wheat bran and of a bulk-forming ispaghula cathartic on the bioavailability of digoxin in geriatric in-patients. Author(s): Nordstrom M, Melander A, Robertsson E, Steen B.

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Source: Drug Nutr Interact. 1987; 5(2): 67-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3038494 •

Interaction of herbal drugs with digoxin. Author(s): Cheng TO. Source: Journal of the American College of Cardiology. 2002 August 21; 40(4): 838-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12204525

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Interaction study between digoxin and a preparation of hawthorn (Crataegus oxyacantha). Author(s): Tankanow R, Tamer HR, Streetman DS, Smith SG, Welton JL, Annesley T, Aaronson KD, Bleske BE. Source: Journal of Clinical Pharmacology. 2003 June; 43(6): 637-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12817526

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Lethal quercetin-digoxin interaction in pigs. Author(s): Wang YH, Chao PD, Hsiu SL, Wen KC, Hou YC. Source: Life Sciences. 2004 January 23; 74(10): 1191-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14697403

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Metabolism of digoxin in relation to therapy in the elderly. Author(s): Caird FI. Source: Gerontol Clin (Basel). 1974; 16(1): 68-74. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4604761

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Morning-evening administration time differences in digoxin kinetics in healthy young subjects. Author(s): Erol K, Kilic FS, Batu OS, Yildirim E. Source: Chronobiology International. 2001 September; 18(5): 841-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11763991

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Neutralization of free digoxin-like immunoreactive components of oriental medicines Dan Shen and Lu-Shen-Wan by the Fab fragment of antidigoxin antibody (Digibind). Author(s): Dasgupta A, Szelei-Stevens KA. Source: American Journal of Clinical Pathology. 2004 February; 121(2): 276-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14983943

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Oleander interference in the digoxin radioimmunoassay in a fatal ingestion. Author(s): Osterloh J, Herold S, Pond S.

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Source: Jama : the Journal of the American Medical Association. 1982 March 19; 247(11): 1596-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7038154 •

Pharmacokinetic interaction of digoxin with an herbal extract from St John's wort (Hypericum perforatum). Author(s): Johne A, Brockmoller J, Bauer S, Maurer A, Langheinrich M, Roots I. Source: Clinical Pharmacology and Therapeutics. 1999 October; 66(4): 338-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10546917

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Positive and negative in vitro interference of Chinese medicine dan shen in serum digoxin measurement. Elimination of interference by monitoring free digoxin concentration. Author(s): Wahed A, Dasgupta A. Source: American Journal of Clinical Pathology. 2001 September; 116(3): 403-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11554169

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Positive and negative interference of the Chinese medicine Chan Su in serum digoxin measurement. Elimination of interference by using a monoclonal chemiluminescent digoxin assay or monitoring free digoxin concentration. Author(s): Dasgupta A, Biddle DA, Wells A, Datta P. Source: American Journal of Clinical Pathology. 2000 August; 114(2): 174-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10941331

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Preparation of beta-methyldigoxin by hydroxylation of beta-methyldigitoxin in fermenter cultures of Digitalis ianata. Author(s): Heins M, Wahl J, Lerch H, Kaiser F, Reinhard E. Source: Planta Medica. 1978 February; 33(1): 57-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=635038

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Quantitative analysis of natural drugs II. Quantitative TLC determination of digoxin and other glycosides in pretreated Digitalis lanata extracts. Author(s): Horvath P. Source: Acta Pharm Hung. 1982 May; 52(3): 133-40. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7090839

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Quinidine enhances digitalis toxicity at therapeutic serum digoxin levels. Author(s): Mordel A, Halkin H, Zulty L, Almog S, Ezra D. Source: Clinical Pharmacology and Therapeutics. 1993 April; 53(4): 457-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8477562

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Renal function and digoxin clearance during quinidine therapy. Author(s): Schenck-Gustafsson K, Juhlin-Dannfelt A, Dahlqvist R.

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Source: Clinical Physiology (Oxford, England). 1982 October; 2(5): 401-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6890426 •

Should digoxin be the drug of first choice after diuretics in chronic congestive heart failure? Author(s): Parmley WW. Source: Journal of the American College of Cardiology. 1988 July; 12(1): 265-73. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3288677

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St John's wort interaction with digoxin. Author(s): Cheng TO. Source: Archives of Internal Medicine. 2000 September 11; 160(16): 2548. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10979073

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The digoxin-propafenone interaction: characterization of a mechanism using renal tubular cell monolayers. Author(s): Woodland C, Verjee Z, Giesbrecht E, Koren G, Ito S. Source: The Journal of Pharmacology and Experimental Therapeutics. 1997 October; 283(1): 39-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9336306

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The Fab fragment of anti-digoxin antibody (digibind) binds digitoxin-like immunoreactive components of Chinese medicine Chan Su: monitoring the effect by measuring free digitoxin. Author(s): Dasgupta A, Lopez AE, Wells A, Olsen M, Actor J. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 2001 July 5; 309(1): 91-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11408010

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The hemodynamic response to digoxin and proscillaridin during rest and exercise in patients with a fixed rate artificial pacemaker. Author(s): Johansson BW. Source: Cardiology. 1972; 57(3): 126-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5064964

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The kinetics of red blood cell electrolyte alterations following digoxin administration. A report of two pediatric cases. Author(s): Loes MW, Lock JE, Singh S, Mirkin BL. Source: Dev Pharmacol Ther. 1981; 3(1): 50-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7307868

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The MDR1 gene product, P-glycoprotein, mediates the transport of the cardiac glycoside, digoxin. Author(s): de Lannoy IA, Silverman M. Source: Biochemical and Biophysical Research Communications. 1992 November 30; 189(1): 551-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1360207

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The use of serum digoxin levels in clinical practice. Author(s): Goldman RH. Source: Jama : the Journal of the American Medical Association. 1974 July 15; 229(3): 331-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4406800

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Treatment of foxglove extract poisoning with digoxin-specific Fab fragments. Author(s): Rich SA, Libera JM, Locke RJ. Source: Annals of Emergency Medicine. 1993 December; 22(12): 1904-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8239114

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Treatment of toad venom poisoning with digoxin-specific Fab fragments. Author(s): Brubacher JR, Ravikumar PR, Bania T, Heller MB, Hoffman RS. Source: Chest. 1996 November; 110(5): 1282-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8915235

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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WebMDHealth: 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 digoxin; 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 Amyloidosis Source: Integrative Medicine Communications; www.drkoop.com Athletic Performance Source: Healthnotes, Inc.; www.healthnotes.com Colds and Flus Source: Prima Communications, Inc.www.personalhealthzone.com Congestive Heart Failure Source: Healthnotes, Inc.; www.healthnotes.com Congestive Heart Failure 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

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Alternative Therapy Naturopathy Source: Integrative Medicine Communications; www.drkoop.com

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Herbs and Supplements Acanthopanax Senticosus Alternative names: Siberian Ginseng Source: Integrative Medicine Communications; www.drkoop.com Albuterol Source: Healthnotes, Inc.; www.healthnotes.com Aloe Alternative names: Aloe vera, Aloe barbadensis, Aloe ferox , Aloe Vera Source: Integrative Medicine Communications; www.drkoop.com

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Aloe Vera Source: Integrative Medicine Communications; www.drkoop.com Aloe Vera Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10001,00.html Asian Ginseng Alternative names: Ginseng, Asian Source: Integrative Medicine Communications; www.drkoop.com Azithromycin Source: Healthnotes, Inc.; www.healthnotes.com Cardiac Glycosides Source: Integrative Medicine Communications; www.drkoop.com Clarithromycin Source: Healthnotes, Inc.; www.healthnotes.com Crataegus Alternative names: Hawthorn; Crataegus oxyacantha L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Crataegus Laevigata Source: Integrative Medicine Communications; www.drkoop.com Crataegus Monogyna Source: Integrative Medicine Communications; www.drkoop.com Cyclosporine Source: Healthnotes, Inc.; www.healthnotes.com Digoxin Source: Healthnotes, Inc.; www.healthnotes.com Digoxin Alternative names: Crystodigin, Lanoxicaps, Lanoxin Source: Prima Communications, Inc.www.personalhealthzone.com Eleuthero Alternative names: Siberian Ginseng, Eleuthero; Acanthopanax/Eleutherococcus senticosus Rupr. & Maxim. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Eleuthero Alternative names: Eleutherococcus senticosus, Acanthopanax senticosus Source: Healthnotes, Inc.; www.healthnotes.com

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Eleuthero Alternative names: Siberian Ginseng Source: Integrative Medicine Communications; www.drkoop.com Eleutherococcus Senticosus Alternative names: Siberian Ginseng Source: Integrative Medicine Communications; www.drkoop.com Ephedra Alternative names: Ephedra sinica, Ephedra intermedia, Ephedra equisetina Source: Healthnotes, Inc.; www.healthnotes.com Erythromycin Source: Healthnotes, Inc.; www.healthnotes.com Fiber Source: Integrative Medicine Communications; www.drkoop.com Ginseng Source: Prima Communications, Inc.www.personalhealthzone.com Glycyrrhiza glabra Alternative names: Licorice Source: Integrative Medicine Communications; www.drkoop.com Glycyrrhiza Alternative names: Licorice; Glycyrrhiza glabra L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Hawthorn Alternative names: Crataegus monogyna, Crataegus laevigata Source: Integrative Medicine Communications; www.drkoop.com Hawthorn Source: Prima Communications, Inc.www.personalhealthzone.com Hawthorn Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10035,00.html Heparin Source: Healthnotes, Inc.; www.healthnotes.com Huperzine A Source: Prima Communications, Inc.www.personalhealthzone.com Hypericum Perforatum Alternative names: St. John's Wort Source: Integrative Medicine Communications; www.drkoop.com

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Klamathweed Alternative names: St. John's Wort Source: Integrative Medicine Communications; www.drkoop.com Licorice Alternative names: Glycyrrhiza glabra Source: Integrative Medicine Communications; www.drkoop.com Licorice Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,801,00.html Loop Diuretics Source: Healthnotes, Inc.; www.healthnotes.com Nefazodone Source: Healthnotes, Inc.; www.healthnotes.com Panax Alternative names: Ginseng; Panax ginseng Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Panax Ginseng Alternative names: Asian Ginseng Source: Integrative Medicine Communications; www.drkoop.com Penicillamine Source: Healthnotes, Inc.; www.healthnotes.com Penicillin V Source: Healthnotes, Inc.; www.healthnotes.com Plantago Major Alternative names: Plantain; Plantago major/lanceolata Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Senna Source: Healthnotes, Inc.; www.healthnotes.com Siberian Ginseng Alternative names: Acanthopanax senticosus Source: Integrative Medicine Communications; www.drkoop.com Spanish Licorice Alternative names: Licorice Source: Integrative Medicine Communications; www.drkoop.com St. John's Wort Alternative names: Hypericum perforatum Source: Integrative Medicine Communications; www.drkoop.com

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St. John's Wort Source: Prima Communications, Inc.www.personalhealthzone.com Theophylline/Aminophylline Source: Healthnotes, Inc.; www.healthnotes.com Thiazide Diuretics Source: Healthnotes, Inc.; www.healthnotes.com Trazodone Source: Healthnotes, Inc.; www.healthnotes.com Tricyclic Antidepressants Source: Healthnotes, Inc.; www.healthnotes.com Valeriana Alternative names: Valerian; Valeriana officinalis Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Warfarin Source: Healthnotes, Inc.; www.healthnotes.com Warfarin Alternative names: Coumadin Source: Prima Communications, Inc.www.personalhealthzone.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 DIGOXIN Overview In this chapter, we will give you a bibliography on recent dissertations relating to digoxin. 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 “digoxin” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on digoxin, we have not necessarily excluded non-medical dissertations in this bibliography.

Dissertations on Digoxin 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 digoxin. 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: •

Correlation of the subcellular distribution of digoxin with the positive inotropic effect in the guinea pig heart by Kim, Nak Doo; PhD from THE UNIVERSITY OF MANITOBA (CANADA), 1971 http://wwwlib.umi.com/dissertations/fullcit/NK10352

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Development of a high-performance liquid chromatographic assay for digoxin in plasma using post-column fluorogenic derivatization by Kwong, Elizabeth; PhD from THE UNIVERSITY OF BRITISH COLUMBIA (CANADA), 1984 http://wwwlib.umi.com/dissertations/fullcit/NL20629

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Development of a sensitive, quantitative high-performance liquid chromatographic assay for the measurement of digoxin in patient groups with high levels of digoxinlike immunoreactive substances by Embree, Leanne; PhD from THE UNIVERSITY OF BRITISH COLUMBIA (CANADA), 1989 http://wwwlib.umi.com/dissertations/fullcit/NL50704

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HPLC analysis of digoxin and digitoxin development of methods for dosage form assay and separation of potential impurities and metabolites by Desta, Belachew; PhD from THE UNIVERSITY OF BRITISH COLUMBIA (CANADA), 1982 http://wwwlib.umi.com/dissertations/fullcit/NK63041

Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.

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CHAPTER 5. PATENTS ON DIGOXIN Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.8 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “digoxin” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on digoxin, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Digoxin By performing a patent search focusing on digoxin, 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

8Adapted

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 digoxin: •

Antidigoxin antibodies Inventor(s): Lingwood; Clifford A. (Toronto, CA) Assignee(s): HSC Research Development Corporation (Toronto, CA) Patent Number: 4,767,720 Date filed: September 10, 1985 Abstract: A digoxin derivative/immunogenic protein conjugate is disclosed which has the carbohydrate moiety of digoxin intact. Antibodies raised against this conjugate show minimal cross-reactivity to digoxin metabolites enabling the use as an antibody in the diagnostic analysis for digoxin when measured in the presence of its metabolites found in serum isolated from a human. Excerpt(s): This invention relates to an immunoassay for digoxin in the presence of its metabolites in serum and the development of antibodies for use in such diagnostic tests. Digoxin is widely used in the treatment of cardiac irregularities. Efficacy of a digoxin dose, as administered to a patient, is dependent on many factors. A narrow therapeutic index necessitates an accurate and reliable means for the measurement of serum digoxin concentration. The measurement for digoxin concentrations in the serum is complicated by the metabolites of digoxin in the serum. There is considerable variation between patients regarding the manner in which digoxin is metabolized in vivo. Digoxin is a steroid-carbohydrate conjugate. A major route of metabolism is the sequential loss of glycose units and/or saturation of the steroid lactone ring. The resulting metabolites retain various degrees of biological and toxic activities of the native digoxin. The presence of metabolites have prevented the accurate measurement of digoxin by standard radioimmunoassay techniques. Serum levels of digoxin have been routinely measured by immunoassay using an antidigoxin antibody raised against a bovine serum albumin-digoxin conjugate immunogen. As described in Butler et al, (1967) Digoxin Specific Antibodies, Proc. Natl. Acad. Sci, 57:71-78, the bovine serum albumin (BSA)digoxin conjugate is prepared by periodate oxidation of the vicinal hydroxyyl groups of the terminal sugar. The generated aldehyde groups are coupled to the amino groups of BSA. Thus the conjugate linkage is through the carbohydrate moiety of digoxin. The antibodies generated in vivo against this conjugate are, therefore, for the most part directed against the steroid moiety of digoxin. Thus, the metabolites, such as digoxigenin bis and monodigitoxide and digoxigenin all react with the antibodies whilst other metabolites such as dihydrodigoxigenin and dihydrodigoxin, where the C22 carbon is reduced, show little or no cross-reactivity with the antibodies. The crossreactivity of the metabolites of digoxin with the antidigoxin antibodies is an appreciated fact and the specifications of most commercial antidigoxin sera state the degree of crossreactivity. It has been found that for some antisera, the carbohydrate metabolites are more potent antigens than digoxin itself, the additional carbohydrate units in some way reducing the antibody binding activity of native digoxin. As a result, there is considerable variation in the anticipated extent to which the glycosidic metabolites may account for the measured digoxin concentration in serum samples. As reported in Soldin, S; Papanastasion-Diamand, A; Heyes, J; Lingwood, C. A. and Olley, P, (1984) Are Immonuassays for Digoxin Reliable? Clin Biochem, 17 317-320, a detailed study of the specificity of the radioimmune assay for digoxin reveals that, in addition to the cross-

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reactivity of the metabolites, some thirty additional cross-reactive, often unrelated compounds have been identified in various serums. Web site: http://www.delphion.com/details?pn=US04767720__ •

Apparatus and method for therapeutic immunodepletion Inventor(s): Halbert; Seymour P. (Miami, FL) Assignee(s): Cordis Laboratories, Inc. (Miami, FL) Patent Number: 4,637,880 Date filed: June 1, 1984 Abstract: A therapeutic apparatus for the removal of a harmful agent from blood is provided in the form of an array of hollow fiber bundles connected in parallel, wherein the interior surfaces of the individual hollow fibers are coated with a covalently bound proteinaceous or other immunoadsorbent selected for specific removal of the harmful agent. In the disclosed method the apparatus is optionally connected as an extracorporeal shunt between the artery and vein of a patient to be treated and the blood is alternately routed through one fiber bundle while the remaining fiber bundles undergo regeneration. Specific embodiments include the removal of rheumatoid factor by covalently bound immunoglobulin G and the removal of digoxin by covalently bound anti-digoxin. Excerpt(s): (2) Abnormal auto-antibodies which are directed against normal tissue constituents, such as rheumatoid factor, anti-DNA, etc. In some of these disturbances, particularly the latter group, recent studies have indicated that plasmapheresis exerts a beneficial therapeutic effect, apparently as a cleansing mechanism. However, plasmapheresis is a relatively crude method of removing unwanted deleterious substances, since it results in the depletion of virtually all plasma constituents, including many essential beneficial ones, in addition to the removal of the harmful agent. Ideally, a highly selective system is required which removes only the unwanted harmful agent, and leaves all the other plasma constituents unchanged in the patient. The resultant therapeutic effects would presumably be considerably more efficient and thorough, with no side effects due to the treatment. Only one approach with the required high degree of selectivity is presently known. This approach involves immunological reagents (antibodies, antigens or haptens), which have been shown to possess remarkable degrees of specificity. The use of such reagents in solid phase has proven feasible in numerous demonstrations during the last 10 to 20 years. Thus, it has been established in the art that antibodies and antigens can be bound covalently to solid supports in a fully reactive state while retaining complete specificity. This "solid phase" technology is the basis for a large proportion of the sensitive radio-immunoassays and enzymeimmunoassays currently used in diagnostic laboratories. Web site: http://www.delphion.com/details?pn=US04637880__

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Assaying of digoxin by means of bioluminescence and inhibition of NA.sup.+ -.sup.+ -ATPase Inventor(s): Kolehmainen; Seppo (Ganzenstraat 11, 3540 Zolder, BE), Tarrkkanen; Veikko (Breulsweg, Wylre 1, NL) Assignee(s): none reported Patent Number: 4,264,727 Date filed: July 24, 1979 Abstract: A method is described for quantitative measurement of digoxin and other digitaloids in serum. The method is based on the inhibition of Na.sup.+, K.sup.+ -specific ATPase enzyme by digitaloids as a result of receptor binding principle and the measurement of this inhibition with the firefly luceferin--luciferase bioluminescence assay of APT. Method is specific and has similar sensitivity to that of the commonly used radioimmunoassay, but simpler and can be performed with low-cost instrumentation. Excerpt(s): The invention relates to a new method for measuring digoxin in serum. Digoxin is a derivative of digitaloids and commonly used for treating patients with heart condition. The action of digoxin and other digitaloids, such as drugs obtained from Digitalis vulgaris plant, inhibit the activity of sodium-potassium specific ATPase enzyme. This ATPase enzyme operates the so called sodium-potassium pump that controls the cell wall permeability of muscle cells and takes part to the constriction of muscle fibres. In the wall of blood vessels there are smooth muscles that are operated by the ATPase. The effect of digitaloid drugs is supposed to be based on the reversible inactivation of sodium-potassium specific ATPase. The inhibition of this enzyme reduces the constriction of the Coronary artery and thus decreasing the possibility of blockage of this vital artery supplying oxygen rich blood to the heart muscle by tromboembolism. Digoxin is presently a most commonly applied drug to prevent thrombosis. This drug is a cardiac glycoside. It has to be applied in narrowly controlled dosage as its mirror is narrow, that is the minimum effective treatment concentration and the toxic concentration, are close to each other. Effective treatment level varies from 0.4-2 ng/cm.sup.3 and concentration over 2 ng are toxic. Web site: http://www.delphion.com/details?pn=US04264727__

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Compounds, compositions and method of treatments for improving circulatory performance Inventor(s): Maroko; Peter R. (1765 Garwood Dr., Cherry Hill, NJ 08003) Assignee(s): none reported Patent Number: 4,761,417 Date filed: October 18, 1985 Abstract: A method of increasing the contractility of the mammalian heart as shown by a positive inotropic affect is disclosed, employing protoberberine alkaloids such as berberrubine or tetrahydropalmitane, alone or in combination with cardiac glycosides such as ouabain, digoxin, digitoxin or delanoside. Excerpt(s): This invention relates to berberine-type alkaloids, particularly protoberberine drug compositions and their use in the treatment and diagnosis of circulatory disorders. The compounds of the invention are of special interest in

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prophylactic, therapeutic and other applications to prevent, minimize, control, alleviate, corect, remedy and so on, various disorders or symptoms of circulatory disorders, including cardiovascular origins or types. The invention relates in terms of subjects (or patients) to the field of mammals, i.e. human and veterinary fields. The invention also encompasses distinct and valuable embodiments like compositions (and compounds and methods of use) for chronic and acute heart failure and other pathologic states that will benefit from an improvement in cardiac performance; for the treatment of shock (cardiogenic and non-cardiogenic shock); for the treatment of arrythmias (whether of natural causes or caused by a drug); for increasing the usefulness of cardiac glycosides (like of the digitalis types) including broadening their usually limited therapeutic index; for controlling or correcting A-V (atrio-ventricular blocks, to be defined later herein) block in mammals. The unique, unobvious and remarkable aspects of the invention are quite numerous and will become apparent hereinafter, but at the outset it is most noteworthy that the compounds of the invention are antiarrhythmogenic, a remarkable utility in and by itself. Another aspect, is that the compounds of the invention have a remarkable combination of beneficial properties, such as, concurrently, having a positive inotropic effect and being antiarrythmogenic. Another unusual aspect is that the compounds of the invention are useful both in acute ventricular failure and also in chronic congestive heart failure. These aspects are of course described in greater detail hereinafter. Web site: http://www.delphion.com/details?pn=US04761417__ •

Coupling agents and products produced therefrom Inventor(s): Allen; Stephen D. (Park City, UT), Thompson; Michael (Evansville, IN) Assignee(s): Becton Dickinson & Company (Paramus, NJ) Patent Number: 4,595,656 Date filed: January 6, 1984 Abstract: Isocyanate or isothiocyanate substituted lactone or thiolactone is employed for coupling one organic compound to another. For example, such coupling agents can be employed for coupling thyroxine or digoxin to a fluorescent compound for use as a tracer in an assay. Excerpt(s): This invention relates to compounds useful for coupling one organic material to another, intermediates useful in producing coupled products, and uses therefor. In many cases, there is a need to couple one organic material to another, and in many cases, such coupling is accomplished by use of a bifunctional compound, often referred to as a coupling agent or spacer compound. For example, in an assay such as an immunoassay, one of the components of the assay is a tracer which is comprised of a ligand such as an antigen, coupled to a suitable marker; e.g., a chromogen, such as a fluorescent dye. In producing such a tracer, in many cases, the antigen is coupled to the fluorescent dye by use of a bifunctional coupling agent or spacer compound. Web site: http://www.delphion.com/details?pn=US04595656__

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Diagnostic immunoassay by solid phase separation for digoxin Inventor(s): Grenier; Frank C. (Libertyville, IL), Kolaczkowski; Lawrence (Vernon Hills, IL), Pry; Terry A. (Libertyville, IL) Assignee(s): Abbott Laboratories (Abbott Park, IL) Patent Number: 4,788,136 Date filed: April 7, 1987 Abstract: A method for performing a diagnostic immunoassay by solid phase separation for digoxin. To a reaction mixture of a test sample and labeled anti-digoxin antibody, which forms a complex of any digoxin present in the test sample, is added a solid phase material having an immobilized ouabain triacetate derivative compound capable of binding any excess labeled antibody. The solid phase material is chosen to rapidly settle whereby a solid and liquid phase is formed. The liquid phase can then be extracted to measure the amount of digoxin-labeled antibody present therein. Ouabain triacetate derivative compounds possess sufficient affinity for anti-digoxin antibodies, and are therefore useful in a solid phase separation based digoxin immunoassay for settling out such antibodies without contributing to undesired background interference. These compounds are also less deleterious to assay performance because of low recognition when leached from the solid phase matrix thereby providing solid phase material with extended shelf life. Excerpt(s): The present invention is directed toward a method and reagents for performing a diagnostic immunoassay for digoxin in biological fluids by a solid-phase separation. The assay employs a solid-phase material having an ouabain triacetate compound immobilized thereon. This method is especially suitable for use in automated systems. Many diagnostic immunoassays are known which generally employ the specific binding characteristics that exist between an analyte or protein with a specific antibody tagged with some traceable substituent. One problem which has long been associated with this method is how to remove excess antibody from the biological fluid being tested for analyte in a manner whereby the analyte concentrations can be accurately measured. Various attempts to remove excess antibody include U.S. Pat. No. 4,298,682 which discloses the absorption of unreacted antibody on a solid phase consisting of a polyacrylamide gel sensitized to the specific antibody. Web site: http://www.delphion.com/details?pn=US04788136__

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Digitalis antibodies, process for the preparation thereof and the use thereof for the therapy of digitalis intoxications Inventor(s): Batz; Hans-Georg (Tutzing, DE), Jungfer; Herbert (Tutzing, DE), Lenz; Helmut (Tutzing, DE), Roder; Albert (Seeshaupt, DE) Assignee(s): Boehringer Mannheim GmbH (Mannheim, DE) Patent Number: 4,742,159 Date filed: December 19, 1983 Abstract: The present invention provides a process for the preparation of digitalis antibodies in which appropriate mammals are immunized with a digoxin bound to protein, the animal serum is obtained, the immune globulin-containing protein fraction is separated in known manner, the immunologically-active globulins are adsorbed on an immunologically-active column and separated from the other proteins, the antibodies

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are again eluted from the column and the Fab fractions are split with papain and purified, wherein, as immunologically-active adsorbent, there is used an inorganic matrix of large surface area to which digitoxin aldehyde is bound via a spacer which cannot be split with papain and the splitting off of the Fab fraction from the antibodies is carried out on the matrix.The present invention also provides digitalis antibodies obtained by this process, which antibodies can be used for the therapy of digitalis intoxications and for preparing immunological reagents for the determination of digitalis glycosides. Excerpt(s): The present invention is concerned with digitalis antibodies, which can be used for the therapy of digitalis intoxications, and with the preparation of such digitalis antibodies. Hitherto, the therapy of digitalis intoxications has been a problem. In the foreground, there was the treatment of the symptoms, especially of the life-threatening disturbances of the heart rhythm, and a forced elimination of glycosides. These measures required several days treatment under intensive care. Nevertheless, the degree of mortality is high: about 20% of the patients die of uncontrollable disturbances of the heart rhythm. In practice, very severe poisonings can occur if the preparations are taken in too high a dosage due to carelessness or as a result of an attempt at suicide or due to kidney failure so that the active material is not eliminated for several days and thereby accumulates in a toxic amount. Therefore, there is a need for an agent which neutralises the toxic action of glycosides in the body and eliminates these quickly and effectively from the body. Web site: http://www.delphion.com/details?pn=US04742159__ •

Digoxigenin immunogens, antibodies, labeled conjugates, and related derivatives Inventor(s): Albarella; James P. (Elkhart, IN) Assignee(s): Miles Laboratories, Inc. (Elkhart, IN) Patent Number: 4,469,797 Date filed: September 23, 1982 Abstract: Immunogen conjugates comprising N-substituted-amino-3-desoxydigoxigenin derivatives coupled to conventional immunogenic carrier materials, and antibodies raised against such conjugates. Also provided are labeled digoxigenin conjugates for use with the digoxigenin antibodies in preferred immunoassay techniques for determining digoxin in biological fluids. Excerpt(s): This invention relates to immunogen conjugates comprising digoxigenin derivatives, particularly carboxy- and amino-functionalized derivatives coupled to conventional immunogenic carrier materials, and anti-digoxin antibodies prepared against such immunogen conjugates. Such antibodies are useful in immunoassays for determining digoxin in biological fluids. The invention also relates to labeled digoxigenin conjugates useful in particularly preferred immunoassay techniques. It is of established medical value to monitor the concentration of digoxin in the bloodstream of patients under treatment with the drug. Immunoassays are the currently most common methods used to determine digoxin in blood samples, e.g., serum or plasma, and are based on the specific binding of anti-digoxin antibodies to the drug in the test sample. Digoxin is a cardiac glycoside consisting of an aglycone, digoxigenin, and three glycosidic digitoxose residues linked to the aglycone at the C-3 position. The glycoside is a hapten, that is, it is incapable of stimulating antibody production unless it is injected into the host animal in the form of a conjugate with an immunogenic carrier material,

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e.g., a protein such as albumin from an animal of a different species. The conventional immunogen conjugate for preparing anti-digoxin antibodies comprises the glycoside chemically linked through a modification of the terminal glycosidic residue to a carrier. The terminal residue is oxidized with periodate to open the ring and form a dialdehyde derivative which is readily couplable to free amino groups in the carrier [Butler and Chen, Proc. Natl. Acad. Sci. USA 57:71(1967), and Smith et al, Biochem 9:331(1970)]. The result is a digoxin-carrier conjugate. Web site: http://www.delphion.com/details?pn=US04469797__ •

Digoxin oxidized product Inventor(s): Wilkinson; Samuel (Beckenham, GB2) Assignee(s): Burroughs Wellcome Co. (Research Triangle Park, NC) Patent Number: 4,184,037 Date filed: January 12, 1978 Abstract: Reagent of value in the radioimmunoassay of digoxin. Also provided by the invention are a radioimmunoassay method utilizing such reagent and a test kit suitable for use in performing the assay. Excerpt(s): This invention relates to a reagent for the assay of a cardiac glycoside in solutions containing it, to the preparation of such reagent, to a method of performing such assays utilizing such reagent, to a test kit suitable for performing such assays, and to a method for making such a test kit. The present invention relates more particularly to a novel reagent for the radioimmunoassay of digoxin. By use of the reagent digoxin may be assayed both in aqueous solution and in solution in mammalian (for example, human) body fluids such as plasma, serum and urine. It is known in the art that the technique of radioimmunoassay may be adapted to the assay of digoxin. In this adapted technique a limiting, fixed quantity of anti-digoxin serum, prepared by standard immunological procedures, is allowed to react with test plasma (or serum or urine) or a standard digoxin solution together with a constant amount of digoxin radioactively labelled in such a manner that the antigenic properties of the molecule are substantially unaffected. Following incubation of the mixture, free digoxin is separated from that bound to anti-body by any of the available procedures and the radioactivity of one or other of the two fractions is measured in a radio-activity counter. The binding of labelled digoxin is progressively inhibited by increasing amounts of unlabelled digoxin due to competition between the two species for the specific binding sites on the antibody. The concentration of digoxin in the plasma under test may readily be determined by reference to a standard curve prepared at the same time. Web site: http://www.delphion.com/details?pn=US04184037__

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Enteric coated digoxin and therapeutic use thereof Inventor(s): Shaffer; Richard D. (Lawrence, KS), Windheuser; John J. (Lawrence, KS) Assignee(s): Interx Research Corporation (Lawrence, KS) Patent Number: 4,147,768 Date filed: May 19, 1978

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Abstract: Therapeutic and undegraded levels of digoxin in warm-blooded animals are achieved by orally admininstering thereto, a non-toxic pharmaceutical enteric-coated tablet comprising:(a) A cardiotonic effective amount of digoxin;(b) a non-toxic pharmaceutically acceptable inert diluent, and(c) a standard non-toxic pharmaceutically acceptable enteric coating.This composition is extremely useful in the treatment of cardiac insufficiency in warm-blooded animals. When administered to warm-blooded animals (e.g., humans), superior therapeutic and undegraded blood levels of digoxin are observed over that normally observed with conventional solid dosage formulations for oral administration. Excerpt(s): The present invention is directed to digoxin and more particularly, a novel and unique solid dosage form for orally administering digoxin to warm-blooded animals, e.g., humans. Digoxin is a cardiotonic drug, used in the field of medicine to achieve an increase in the force of myocardial contraction. Essentially, digoxin is a conduction system depressant which acts in such a manner as to decrease cardiac rate. Digoxin is used in the treatment of cardiac failure, atrial fibrillation and flutter, paroxysinal tachycardia, cardiac insufficiency, etc. This compound has the advantage as compared to digitoxin, and that its onset of action is quite more rapid, and further, its duration of action is relatively shorter. This compound has an additional advantage in that in the event of an overdose, the symptoms associated therewith are more readily dissipated. Web site: http://www.delphion.com/details?pn=US04147768__ •

Heterogeneous immunoassay for digoxin using ouabain as a separation means Inventor(s): Chang; Shung-Ho (Encinitas, CA), Freytag; William J. (Wilmington, DE) Assignee(s): E. I. Du Pont de Nemours and Company (Wilmington, DE) Patent Number: 4,551,426 Date filed: January 18, 1984 Abstract: A heterogeneous immunoassay for digoxin. An excess of labeled anti-digoxin antibody is added to a test sample and the resulting reaction mixture is contacted with a solid phase having ouabain immobilized thereon. All the free, labeled antibody binds to the oubain. The eluted digoxin anti-digoxin antibody complex is measured for label activity. A competitive mode is also disclosed. Excerpt(s): This invention relates to an improved immunoassay for digoxin and, more specifically, to a noncompetitive heterogeneous immunoassay employing a labeled, monovalent or divalent anti-digoxin antibody as the indicator reagent and a column of immobilized ouabain as the means for effecting a separation. A large and expanding market exists for clinical laboratory diagnostic tests capable of determining rapidly and accurately the concentration of digoxin present in biological fluids. Digoxin frequently is present at concentrations of nanomolar or less. In recent years, a number of immunoassay techniques have been developed for the measurement of clinically important ligands. Typically, a competitive binding immunoassay consists of a conjugate of a labeling substance linked to a binding component which participates in a binding reaction to produce two species of the labeled conjugate, a bound species and a free species. The relative amounts of the labeled conjugate that result in the bound species and the free species are a function of the concentration of the ligand to be detected in the test sample. Web site: http://www.delphion.com/details?pn=US04551426__

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Homogeneous amperometric immunoassay Inventor(s): Aizawa; Masuo (2-19-4 Amanuma, Suginami-ku, Tokyo 167, JP), Hidaka; Miki (2040 Pelham Ave., Los Angeles, CA 90025), Manning; Brenda D. (158 Canton St., North Easton, MA 02356), Uretsky; Laura S. (9-1 Shadowbrook La., Milford, MA 01757) Assignee(s): none reported Patent Number: 5,198,367 Date filed: June 9, 1989 Abstract: A method is described for measuring the amount of analyte present in a sample containing the analyte using a homogeneous amperometric immunoassay. The analyte is covalently bonded to a suitable carrier molecule, which is also covalently bonded to an electroactive molecule. The electroactive molecule, such as ferrocene carboxylic acid, contains a redox center which is capable of transferring a charge to an electrode. A preferred carrier molecule is bovine serum albumin (BSA), while suitable analytes include digoxin, theophylline and HCG. The immunoassay is conveniently performed by applying a voltage to a set of electrodes. Excerpt(s): The present invention relates to an electrochemical immunoassay which can be used for detecting the presence of analytes such as digoxin, theophylline, creatine kinase (CKMB) and human chorionic gonadotrophin (HC). The improvement of this invention involves the use of a complex comprising an electroactive molecule, a carrier molecule and the analyte of interest, in a homogeneous immunoassay. Electrochemical detection methods are widely employed in the clinical diagnostic market since these methods are relatively inexpensive and simple to use. Heterogeneous electrochemical immunoassay systems frequently require a high degree of operator involvement, due to extensive washing steps and multiple reagent additions, when sensitivities of better than 10.sup.-6 M are desired. Even this level of sensitivity is insufficient for the detection of smaller analytes of clinical significance, such as digoxin, and the detection of most larger analytes such as CKMB and HCG. For instance, digoxin, which is a cardiac glycoside widely used for treating congestive heart failure and other acute cardiac conditions, is a potent drug having a therapeutic effect at concentrations as low as 1 nmol/L with a small therapeutic index. However, digoxin can also be toxic at low concentrations, with the dosage required to produce therapeutic effects and the sensitivity to toxicity being dependent on the particular patient undergoing treatment. Rapid detection of digoxin in the nanomolar range is required for treating cardiac patients, and any useful detection method for digoxin must be capable of measuring nanomolar concentrations with a rapid response time. These problems could be solved by employing a homogeneous system of higher sensitivity, but to date the development of such a system has been elusive. The difficulty in developing such systems based on nonenzymatic electroactive labelling for electrochemical immunoassays is described by W. R. Heineman et al in Methods of Biochemical Analysis, 32, pages 345-393 (1986). The use of homogeneous electrochemical immunoassays for detecting the presence of theophylline has been reported in M. Haga et al in Analytical Biochemistry, 118, pages 286-293 (1981), using a liposome immunosensor employing liposomes which contain entrapped enzymes whose activity is directly proportional to the lysis of the liposome and inversely proportional to the concentration of free antigen in the sample. When a current pulse is introduced into the sample, the enzyme catalyzes the depletion of oxygen which is detected by an oxygen electrode, and the current registered. The incorporation of electroactive molecules within liposomes is reported in R. M. Kannuck et al in Analytical Chemistry, 60, pages 142-147 (1988), which describes the encapsulation of potassium ferrocyanide within liposomes for signal amplification. The

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liposome binds with an antibody present in the sample, releasing the encapsulated potassium ferrocyanide, which transmits a charge to the electrode surface. Electroactive liposome technology, while of theoretical interest, is difficult to utilize in practice and can produce false readings due to the instability of the liposomes employed in such systems. Web site: http://www.delphion.com/details?pn=US05198367__ •

Medication and method for treating heartworms in dogs Inventor(s): Tisdale; John W. (935 S. 3 Notch St., Andalusia, AL 36420) Assignee(s): none reported Patent Number: 4,789,548 Date filed: April 24, 1986 Abstract: A medication and method for treating heartworms in dogs, which medication includes a time release capsule or tablet dosage structure which is characterized either by discrete elements (capsule) or an outer layer or layers (tablet) of vasoconstricting and bronchial dilating medications and an inner, time-released layer or pellets of diethylcarbamazine. The vasoconstrictors and bronchial dilators are designed to counteract life-threatening vasodilation and bronchial constriction resulting from the release of acetylcholine by the dog when the heartworms are attacked by the diethylcarbamazine. The solid dosage structure can be constructed by layering such vasoconstrictors and bronchial dilators as prednisone, ephedrine, digoxin and dextroamphetamine sulfate in separate layers or combining these ingredients in a single layer separated from the diethylcarbamazine by a time-release substance such as gelatin. The capsule dosage structure includes discrete beads or elements of the medications in a capsule containing a time release, therapeutic dosage of the diethylcarbamazine. Alternatively, the vasoconstrictors and bronchial dilator medications can be injected or administered orally prior to treatment with the diethylcarbamazine according to the method of this invention. Excerpt(s): This invention relates to the treatment of heartworms or adult filaria in the heart and circulatory systems of dogs. More particularly, the invention relates to a combined preventative treatment and therapeutic treatment for dogs infested with adult filaria by using vasoconstrictors and bronchial dilators, as well as cardiac and sympathetic stimulants to counteract the effects of therapeutic treatment with diethylcarbamazine. Since it is speculated that the treatment of adult filaria with diethylcarbamazine results in the release of a toxin which causes the body to secrete acetylcholine, a chemical which acts to produce massive vasodilation and bronchial constriction in the animal, treatment of the adult filaria requires application of both preventative and therapeutic medicine. The preventative treatment is designed to use certain vasoconstricting, bronchial dilating and/or cardiac and sympathetic stimulant medication such as prednisone, ephedrine, digoxin and dextroamphetamine sulfate to counteract the undesirable vasodilation and bronchial constriction with resulting cardiac weakening in dogs which are treated with the diethylcarbamazine. The adult heart worm parasite or "filaria" slowly and painfully kills hundreds of thousands of dogs annually. The parasite is particularly prolific in the coastal states, where it is estimated that at least 80 percent of all dogs which remain outside in mosquito-infested areas will have an infestation of heartworms before they reach three years of age. None of the currently used veterinary treatments are highly effective and safe, and most cause severe pain, swelling and in some cases, necroses of the tissues. Diethylcarbamazine has

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been used for years under a variety of trademarks such as "Caricide", a trademark of the American Cyanimid Company, for the treatment of adult filaria or "filiariasis" in dogs. Caricide was used during Word War II to treat filiariasis in human patients in the south pacific theatre where infestation became a problem in American troops in that area. Diethylcarbamazine was used throughout the 1950's and 1960's by veterinarians as a successful treatment of healthy dogs for infestations of dirofilaria immitis, which is the most common species of adult filaria infecting dogs in the coastal United States. Sometime after the era of the 1960's, Caricide was discontinued due to complaints that various side effects and occasional deaths occurred from its use in heavily affected dogs having large numbers of worms in the heart. This supposed drug-sensitivity reaction was noted to be more prevalent in weak and emaciated dogs which were subjected to long-standing stress from the infestataions and it was observed to only occurr in a small percentage of those dogs treated. Web site: http://www.delphion.com/details?pn=US04789548__ •

Method and kit for determining total digoxin levels involving agent to dissociate digoxin-protein complex Inventor(s): Farrenkopf; Bruce C. (Clifton, NJ), Kaufman; Richard A. (Belleville, NJ) Assignee(s): Hoffmann-La Roche Inc. (Nutley, NJ) Patent Number: 4,698,315 Date filed: April 22, 1985 Abstract: A method for determining total digoxin levels in a biological fluid sample containing digoxin-protein complex which method comprises disrupting the digoxinprotein complex by treating said sample solution with an effective amount of a dissociation agent selected from one or more members of the group consisting of a C.sub.3 -C.sub.26 saturated or unsaturated fatty acid, a C.sub.2-7 lower alkanol, quinidine and.alpha.-tocopherol so as to release the bound digoxin from serum protein, passing the treated sample solution through a centrifugal ultrafilter so as to selectively pass digoxin containing sample solution through said filter and retaining said serum proteins and determining the digoxin contents in said sample solution in a fluorescence polarization assay. A kit for carrying out the method is provided. Excerpt(s): For an assay to be accurate, where the analyte concentration is read off a standard curve, the standards and patient samples must behave indentically in the assay. Perhaps one of the most critical factors between the standards and the patient samples is that the recovery of analyte from the standards must be identical to the recovery of the analyte from the patient samples or erroneous values will result. This is particularly true if the total quantity of analyte in the patient sample is being measured. In fluorescent polarizaton assays of analytes in serum, one of the undesirable features of this methodology is the high fluorescence background of the serum. This becomes particularly troublesome when low levels of analytes like digoxin are being measured. In this case, the assay is not feasible using serum directly with a fluorescein-labeled digoxin tracer since the serum background fluorescence far exceeds the fluorescence signal emitted by the fluorescein-labeled digoxin tracer. In order to overcome the high background fluorescence of the serum, protein-free filtrates have typically been made using perchloric or trichloroacetic acids. Although the methods are effective in producing a protein-free filtrate relatively free of background fluorescence, they suffer from other disadvantages. In the case of digoxin, relatively poor recovery is obtained in

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the supernatant, and in addition the recovery is dependent on the protein concentration in the sample. See for example Porter et al., Clin. Chem. 30, 1826-1829 (1984). Web site: http://www.delphion.com/details?pn=US04698315__ •

Method and preparation for increasing bioavailability of digoxin Inventor(s): Cresswell; Ronald M. (Raleigh, NC), Holstius; Elvin A. (Greenville, NC) Assignee(s): Burroughs Wellcome Co. (Research Triangle Park, NC) Patent Number: 4,088,750 Date filed: January 28, 1976 Abstract: Method and preparation for increasing the bioavailability of digoxin to treat cardiac insufficiency in a human, said method comprising the administration of a preparation comprising a capsule adapted to release a solution of digoxin in an amount sufficient to treat cardiac insufficiency. Excerpt(s): The present invention is directed to the discovery of a new and improved method of increasing the bioavailability (concentration) of digoxin in the blood by administering a soft gelatin capsule containing a solution of digoxin. With the present invention substantially higher concentrations of digoxin in the blood are achieved in comparison with using tablets containing the same amount of digoxin or the same solution of digoxin as in the capsule given orally without being encapsulated. This invention also relates to pharmaceutical preparations containing a solution of digoxin in a capsule which will rapidly release digoxin for uptake preferably in the upper gastrointestinal tract of a human. The glycoside digoxin, chemically named 3.alpha.-tri(.beta.-D-digitoxosyl)oxy-12.alpha.,14.beta.-dihydroxy-5.beta.-card-20(22)-enolide, has found extensive use in the treatment of human patients with cardiac insufficiency. As used herein the term cardiac insufficiency is intended to include congestive heart failure, atrial fibrillation, atrial flutter, supraventricular tachycardia and premature extrasystoles. Web site: http://www.delphion.com/details?pn=US04088750__

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Method for improving morbidity and/or mortality Inventor(s): Cropp; Anne Barbara (Madison, CT) Assignee(s): Pfizer Inc. (New York, NY) Patent Number: 5,948,799 Date filed: March 12, 1997 Abstract: This invention relates to a method for reducing morbidity and/or mortality in a mammal with congestive heart failure due to non-ischemic etiology comprising administering amlodipine or a pharmaceutically acceptable amlodipine acid addition salt, and, optionally, a diuretic and/or digoxin. The invention further relates to methods for treating patients with congestive heart failure due to non-ischemic etiology, comprising administering a non-ischemic congestive heart failure treating amount of amlodipine or a pharmaceutically acceptable amlodipine salt and, optionally, a diuretic and/or digoxin. The invention also provides a kit which comprises a container means and a) amlodipine and a diuretic, b) amlodipine and digoxin, or c) amlodipine, digoxin and a diuretic; and a kit which comprises a container means and a) amlodipine, an

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angiotensin converting enzyme (ACE) inhibitor and a diuretic, b) amlodipine, an ACE inhibitor and digoxin, or c) amlodipine, an ACE inhibitor, digoxin and a diuretic. Further, this invention relates to compositions comprising amlodipine or a pharmaceutically acceptable salt thereof and one or both of digoxin and/or a diuretic. Excerpt(s): This invention relates to: a method for reducing morbidity and/or mortality in a mammal with congestive heart failure due to non-ischemic etiology comprising administering amlodipine or a pharmaceutically acceptable amlodipine acid addition salt, and, optionally, a diuretic and/or digoxin; methods for treating patients with congestive heart failure due to non-ischemic etiology, comprising administering a nonischemic congestive heart failure treating amount of amlodipine or a pharmaceutically acceptable amlodipine salt and, optionally, a diuretic and/or digoxin; compositions comprising a) amlodipine and a diuretic, b) amlodipine and digoxin, or c) amlodipine, digoxin and a diuretic; a kit which comprises a container means and a) amlodipine and a diuretic, b) amlodipine and digoxin, or c) amlodipine, digoxin and a diuretic; and a kit which comprises a container means and a) amlodipine, an angiotensin converting enzyme (ACE) inhibitor and a diuretic, b) amlodipine, an ACE inhibitor and digoxin, or c) amlodipine, an ACE inhibitor, digoxin and a diuretic. Congestive heart failure, regardless of its etiology, is characterized by a weakness of the myocardial tissue of the left and/or right ventricle of the heart to pump and thereby circulate blood into systemic and/or pulmonary circulations. It is accompanied by circulatory and neurohumoral changes which result in failure to deliver sufficient blood and oxygen supply to peripheral tissues and vital organs. If left untreated, the health of a patient with congestive heart failure could progress to the point where the disease would be fatal. Survival data from patients with overt congestive heart failure in the Framingham Heart Study indicate persisting high lethality without significant temporal prognostic improvement during the 40 year period 1948-1988 (Ho K K L, Anderson K M, Kannel W B, Grossman W, Levy D. Survival after the onset of congestive heart failure in Framingham Heart Study subjects. Circulation 1993; 88: 107-115). Over the years a precise definition of heart failure has remained elusive. Heart failure is generally characterized by an inadequacy of the heart, usually in association with elevated central cardiac filling pressures, to meet the metabolic demands of peripheral organs and tissues either at rest or during stress. The lack of a uniformly accepted definition of heart failure and the myriad of patient subsets within this heterogenous diagnosis present a considerable challenge to the practicing physician selecting therapy. Web site: http://www.delphion.com/details?pn=US05948799__ •

Methods and reagents for performing ion-capture digoxin assays Inventor(s): Adamczyk; Janina (Gurnee, IL), Berry; Daniel S. (Libertyville, IL), Fico; Rosario M. (Zion, IL), Jou; Yi-Her (Libertyville, IL), Kline; Steven (Grayslake, IL), Markese; James J. (Downers Grove, IL), Stroupe; Stephen D. (Libertyville, IL) Assignee(s): Abbott Laboratories (Abbott Park, IL) Patent Number: 5,459,078 Date filed: June 9, 1993 Abstract: The present invention includes novel digoxin assays employing a capture reagent, involving a first binding member conjugated to a polymeric anion substance, and a solid phase material containing a reaction site comprising a polymeric cation substance having a nitrogen content of at least about two percent. A test sample suspected of containing the analyte of interest may be contacted with the capture

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reagent to form a charged capture reagent/analyte complex. The complex is then contacted to the oppositely charged solid phase to attract, attach, and immobilize the capture reagent/analyte complex. Excerpt(s): This invention relates generally to the field of binding assay devices and methods. In particular, the present invention relates to novel devices useful in the performance of homogeneous immunoassays. Various analytical procedures and devices are commonly employed in assays to determine the presence and/or concentration of substances of interest or clinical significance which may be present in biological liquids or other materials. Such substances are commonly termed "analytes" and can include antibodies, antigens, drugs, hormones, etc. Immunoassay techniques take advantage of the mechanisms of the immune systems of higher organisms, wherein antibodies are produced in response to the presence of antigens which are pathogenic or foreign to the organisms. These antibodies and antigens, i.e., immunoreactants, are capable of binding with one another, thereby creating a highly specific reaction mechanism which can be used in vitro to determine the presence or concentration of that particular antigen in a biological sample. Web site: http://www.delphion.com/details?pn=US05459078__ •

Monoclonal antibody with a high affinity for digoxin Inventor(s): Struck; Carl-Julius (Wiesbaden, DE) Assignee(s): Boehringer Ingelheim KG (Ingelheim am Rhein, DE) Patent Number: 4,703,003 Date filed: August 13, 1984 Abstract: A hybridoma which produces monoclonal antibodies having a high affinity and selectivity for digoxin is produced by immunizing mice with digoxin, fusing the spleen cells from the treated mice with mice myeloma cells, separating hybrids from non-fused cells, selecting the hybrids which produce monoclonal antibodies directed against digoxin and isolating the hybrids. Excerpt(s): This invention relates to a monoclonal antibody with a high affinity for the digitalis glycoside digoxin and a low sensitivity to related glycosides and sprionolactone, to the cell lines which produce this monoclonal antibody, to processes for the preparation thereof, to the use of this antibody, and to a test system containing this monoclonal antibody. At present, millions of coronary patients throughout the world are treated with digitalis glycosides [J. R. Ochs, G. Bodem, Med. Welt 30, 602 (1978)]. Thus, this group of preparations are among the drugs most frequently prescribed. Within the entire group, digoxin plays the most important part, having a share of over 90%. However, the wide distribution and frequent use of the digitalis glycosides should not conceal the fact that these are potentially dangerous substancestheir therapeutic range is extremely small. Therefore, in order to achieve an effective and safe therapy, it is essential to monitor the digitalis level continuously. A series of different test procedures have been developed for this purpose wherein the antibodies formed against the glycoside by the body are used as test reagents. These antibodies are obtained from the serum of host animals immunized with digitalis. In this way, antisera of a polyclonal nature are obtained, that is, these sera contain different antibodies. Web site: http://www.delphion.com/details?pn=US04703003__

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Pharmaceutical compositions containing cardiac glycoside Inventor(s): Fadda; Carlo (Rome, IT) Assignee(s): R. P. Scherer Limited (EN) Patent Number: 4,067,960 Date filed: December 1, 1976 Abstract: A cardiotonic dosage unit form comprises a soft gelatine capsule containing a liquid cardiotonic composition comprising (a) a cardiac glycoside, preferably digitoxin or digoxin; (b) dimethyl formamide or dimethyl acetamide; and (c) a liquid polyethylene glycol and also, optionally, (d) propylene glycol or glycerin.The weight ratio of dimethyl acetamide or dimethyl formamide to cardiac glyceride is preferably at least 5:1 and the polyethylene glycol preferably forms at least 75% by weight of the total composition contained in the gelatine capsule. Excerpt(s): This invention is concerned with improvements in and relating to pharmaceutical compositions and, more particularly, relates to cardiotonic compositions containing, as active ingredient, a cardiac glycoside derived from Digitalis purpurea or Digitalis lanarta or a derivative thereof. For the sake of convenience such materials will hereinafter be simply referred to as "cardiac glycosides". Cardiac glycosides are widely used cardiotonic agents and are commonly formulated as tablets for oral administration. Of necessity, each tablet must contain a very small amount of the active ingredient, (e.g. 250 micrograms or less) since these particular active agents are administered in such very small doses, almost always less than 0.5 mg. The fact that each tablet has to contain so little of the active ingredient gives rise to problems in formulation and, in particular, makes it very difficult to ensure perfect compounding of the tableting mix so that each tablet contains the same amount, with tolerable limits, of the active ingredient, (see, for example, Thomas et al, The Lancet, December 1, 1973, pp 1267-8; Fraser et al, 5, Pharm. Pharmac., 1973, 25, pp 268-973; and Shaw et al, British Medical Journal, 1973, 4, pp 763766). It is an object of the present invention to provide an improved dosage unit suitable for the oral administration of a cardiac glycoside. Web site: http://www.delphion.com/details?pn=US04067960__

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Precipitation of interfering proteins in fluorescence polarization immunoassay for digoxin Inventor(s): Hockerman; Gloria J. (Kenosha, WI), Wang; Philip P. (Libertyville, IL) Assignee(s): Abbott Laboratories (North Chicago, IL) Patent Number: 4,734,378 Date filed: June 26, 1985 Abstract: Interfering proteins are precipitated and digoxin extracted in a fluorescence polarization immunoassay for digoxin with a protein precipitating reagent. The reagent contains about 3 to 4% 5-sulfosalicyclic acid in an aqueous solution including about 40 to 60% of a straight or branch chained organic alcohol having from 1 to 4 carbon atoms. Excerpt(s): This invention relates generally to fluorescence polarization immunoassays and reagents useful therein, and particularly to such an assay for the analyte digoxin in a biological fluid, wherein the assay is improved by the use of a novel precipitation reagent which is effective to extract both the analyte and to precipitate interfering proteins. Digoxin is a potent cardiac glycoside widely prescribed for the treatment of

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patients suffering from congestive heart failure, as well as some types of cardiac arrhythmias. Digoxin intoxication is a common and serious problem in the clinical setting. This is, in part, because cardiac glycosides have a low therapeutic ratio (a very small difference between therapeutic and toxic tissue levels). Coupled with the low therapeutic ratio is a marked patient variability in response to the same dosage of drug, resulting in often unpredictable drug serum levels. Intoxication symptoms are often indistinguishable from the original condition for which the drug was prescribed, and it may not be readily apparent whether the patient has been under- or over-dosed. Monitoring of serum or plasma digoxin levels combined with other clinical data can provide the physician with useful information to aid in adjusting patient dosage, achieving optimal therapeutic effect while avoiding useless subtherapeutic or harmful toxic dosage levels. Conventional monitoring of digoxin levels in biological fluids such as serum, plasma, urine, spinal and amniotic fluid and the like, has typically depended on commercially available radioimmunoassays (RIA) and nonisotopic assays such as fluorescence polarization immunoassays (FPIA). Certain methodological problems with various commercially-available RIA for digoxin have produced inconsistencies in results from these methods. It has been theorized that variations in the albumin concentration of individual patient serum or plasma samples and in the digoxin standards used, as well as the presence of digoxin-like immunoreactive and/or other presently unidentified substances (especially in patients with renal failure), may account for discrepencies observed between different types of RIA (See W. H. Porter, et al., Effect of Protein Concentration on the Determination of Digoxin in Serum by Fluorescence Polarization Immunoassay, Clin. Chem. 30/11, 1826-1829 (1984)). Web site: http://www.delphion.com/details?pn=US04734378__ •

Process for the preparation of.beta.-methyldigoxin Inventor(s): Franzmair; Rudolf (Linz, AT) Assignee(s): Chemie Linz Aktiengesellschaft (Linz, AT) Patent Number: 4,603,196 Date filed: May 21, 1984 Abstract: The invention relates to a process for the preparation of.beta.-methyldigoxin by the selective methylation of digoxin with dimethyl sulfate in the presence of a basic strontium compound and, if appropriate, of an inert inorganic adsorbent. Strontium hydroxide octahydrate, strontium methylate or strontium hydroxymethylate is used as the basic strontium compound, and an oxide, silicate or phosphate of magnesium, calcium, aluminum, silicon or titanium, with a water content in the range of 0 to 20% by weight, is used as the inorganic adsorbent. The reaction is carried out at temperatures of -15.degree. to 15.degree. C. in the presence of 3 to 24 moles of water per mole of digoxin, the water being introduced in the reaction mixture by the water content of strontium hydroxide octahydrate and/or the inorganic adsorbent used and purification of the methylation product so formed by column chromatography on SiO.sub.2 with a mixture of chlorohydrocarbon and a lower aliphatic alcohol. Excerpt(s): The invention relates to a process for the preparation of 4"'-O-methyldigoxin (.beta.-methyldigoxin) by the partial methylation of digoxin. The preparation of digoxin monoalkyl ethers by the monoalkylation of digoxin is known from the patent literature. In the process of British patent specification 1,168.970 the partial monomethylation of the 3"'- or 4"'-hydroxy group on the terminal digitoxose can be carried out with the customary methylating agents, such as diazomethane or dimentyl sulfate, under the

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process conditions which are in themselves known. However, in the methylation with dimethyl sulfate, diagoxin polyethers are formed in amounts of 20 to 30% by weight as by-products, and these can no longer be demethylated to give digoxin or monomethyldigoxin. These by-products must be separated off chromatographically and represent a considerable loss of expensive starting material. The use of the poisonous and explosive diazomethane for the monomethylation of digoxin is not suitable for a large-scale manufacturing process. Web site: http://www.delphion.com/details?pn=US04603196__ •

Process of determining an immunogenic substance by competition with an antibody in a microcapsule Inventor(s): Lim; Franklin (Richmond, VA), Moss; Richard D. (Chester, VA) Assignee(s): Damon Corporation (Needham Heights, MA) Patent Number: 4,255,411 Date filed: November 27, 1978 Abstract: A process for determining an immunogenic substance present in a sample wherein the immunogenic substance in the sample competes with a distinguishable analog of such substance for available binding sites on an antibody which is highly specific for the immunogenic substance in the sample. The antibody is encapsulated in a semi-permeable microcapsule.A specific example of the foregoing procedure is the determination of digoxin present in serum wherein the digoxin in the serum competes with radioiodine labeled digoxin for available binding sites on an antibody which is highly specific for digoxin and has been previously encapsulated in semi-permeable microcapsules. The concentration of digoxin in the sample is determined from a standard curve by relating digoxin concentration inversely to the percent of radioiodine labeled digoxin that is complexed to the antibody. Excerpt(s): A common known procedure for determining the amount of an antigen in a sample is to allow the antigen in the sample to compete with a distinguishable analog of the antigen for sites on an antibody which is highly specific for the antigen. This general method of determining the amount of antigen present is known as a competitive system. For example, if the amount of digoxin present in the serum is to be determined, an aliquot of the serum and an aliquot of radioactively labeled digoxin is allowed to react with an antibody specific for digoxin. The labeled and unlabeled digoxin compete for sites on the antibody. Thus, the greater the amount of digoxin in the sample, the lower will be the radioactive reading on the antibody. Two common methods of performing such competitive determinations are known as "liquid phase radioimmunoassay" and "solid phase radioimmunoassay". In each system the immunogenic substance which is bound to an antibody must be removed from unbound immunogenic substance in order to make a measurement of the amount of labeled analog on the antibody. From this measurement, the amount of immunogenic substance in the sample is determined. In "liquid" phase radioimmunoassay systems, the antibody, labeled analog and immunogenic substance to be determined are incubated in solution. A number of antibody binding sites are available and reaction time is rapid. To separate the antibody complexed immunogenic substance from the uncomplexed immunogenic substance, the antibody immunogenic complex is precipitated, centrifuged, and the supernatant is decanted. Web site: http://www.delphion.com/details?pn=US04255411__

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Serum pretreatment for digoxin assay Inventor(s): Ernst; Roberta D. (Sunnyvale, CA), Khanna; Pyare (San Jose, CA), Stone; Anne J. (Los Altos, CA) Assignee(s): Syntex (U.S.A.) Inc. (Palo Alto, CA) Patent Number: 4,654,311 Date filed: June 15, 1984 Abstract: Serum is passed through a column containing silica gel alkylated with lower alkyl groups. The column is then washed with diluted acid and water, and the digoxin eluted with aqueous methanol at a volume less than about the volume of the serum to provide a digoxin concentrate that may be used in assay determinations. Excerpt(s): Digoxin, and derivatives of digoxin, find wide use in cardiac treatment, frequently as a component of digitalis. Digoxin is highly potent in its activity and has a narrow therapeutic range. In addition, the drug can produce serious side effects, so that monitoring the digoxin level in blood is important for the well-being of the patient. Since the therapeutic range is from about 0.8 to 2.0 ng/ml, it is necessary no only to measure extremely small amounts of digoxin in serum, but also to be able to distinguish between small differences in concentrations. Depending upon the sensitivity of the assay, the digoxin concentration in serum may be insufficient for detection when diluted into the assay medium. Also, naturally occurring materials in the serum sample may modify the observed signal so as to give false results. It would therefore be desirable to provide for a simple means for pretreatment of a serum sample for a digoxin assay. The pretreatment method should be rapid and efficient and provide an assay sample containing the drug in a concentrated amount free of interfering substances. A radioimmunoassay for determining the digoxin content of a sample is disclosed in U.S. Pat. No. 3,981,982. An enzyme amplification assay is described in U.S. Pat. No. 3,817,837. Web site: http://www.delphion.com/details?pn=US04654311__

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Serum pretreatment in digoxin immunoassay Inventor(s): Khanna; Pyare (Fremont, CA), Pearlman; Fred (Union City, CA) Assignee(s): Syntex (U.S.A.) Inc. (Palo Alto, CA) Patent Number: 4,798,804 Date filed: February 5, 1987 Abstract: A method is disclosed for preparing a sample suspected of containing digoxin for determination of digoxin in the sample during an assay. The method comprises contacting the sample with.beta.-cyclodextrin in an amount and under conditions sufficient to allow a substantial portion of digoxin in the sample to bind to the.beta.cyclodextrin. The.beta.-cyclodextrin with bound digoxin is separated from at least one other component of the medium. Next, the digoxin is released from the.beta.cyclodextrin to provide a sample containing digoxin which may be analyzed by any of a number of assay techniques. Excerpt(s): Digoxin, and derivatives of digoxin, find wide use in cardiac treatment, frequently as a component of digitalis. Digoxin is highly potent in its activity and has a narrow therapeutic range. In addition, the drug can produce serious side effects, so that monitoring the digoxin level in blood is important for the well-being of the patient.

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Since the therapeutic range is from about 0.8 to 2.0 ng/ml, it is necessary not only to measure extremely small amounts of digoxin in serum, but also to be able to distinguish between small differences in concentrations. Depending upon the sensitivity of the assay, the digoxin concentration in serum may be insufficient for detection when diluted into the assay medium. Also, naturally occurring materials in the serum sample may modify the observed signal so as to give false results. It would therefore be desirable to provide for a simple means for pretreatment of a serum sample for a digoxin assay. The pretreatment method should be rapid and efficient and provide an assay sample containing the drug in a concentrated amount free of interfering substances. A radiommunoassay for determining the digoxin content of a sample is disclosed in U.S. Pat. No. 3,981,982. An enzyme amplification assay is described in U.S. Pat. No. 3,817,837. Web site: http://www.delphion.com/details?pn=US04798804__

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

19-norbufalin derivatives, their preparation and pharmaceutical compositions containing them Inventor(s): Deutsch, Joseph; (Jerusalem, IL), Lichstein, David; (Jerusalem, IL) Correspondence: Lerner, David, Littenberg,; Krumholz & Mentlik; 600 South Avenue West; Westfield; NJ; 07090; US Patent Application Number: 20030162701 Date filed: April 10, 2003 Abstract: A 19-norbufalin derivative compound of formula (I) and isomers pharmaceutically acceptable salts thereof. Compounds of formula (I) are Na.sup.+,K.sup.+-ATPase inhibitors and can be used in the treatment of cardiac and/or vascular malfunction, renal malfunction, as digoxin antagonists, for treatment of CNS disorders and for the treatment of malignant and proliferative cell diseases. Excerpt(s): The invention relates to novel 19-norbufalin derivatives and processes for their preparation. The novel norbufalin derivatives are inhibitors of Na.sup.+, K.sup.+ATPase activity and can be used in the treatment of cardiovascular, kidney and malignant and proliferative cell diseases. Endogenous bufodienolides having digitalislike activity were identified in material extracted and purified from human cataractous lenses by chemical ionization mass spectroscopy, together with UV spectroscopy and biological characterization, as 19-norbufalin and 19-norbufalin peptide conjugate [Lichtstein D., et al., Eur. J. Biochem. 216:261-268 (1993); U.S. Pat. No. 5,874,423]. Since 1969 several attempts to synthesize bufodienolides were reported [Soncheimer F., et al., J. Am. Chem. Soc. 91:1228-1230 (1969); Stache U., et al., Tetrahedron Lett., 35:3033-3038 (1969); Pettit G. R., et al., Can. J. Chem., 47:2511 (1969); Pettit G. R., et al., J. Org. Chem., 35:1367-9 (1970)]. In all reports the starting material was a steroid compound in which

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

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the functional groups were altered in order to produce the active bufadienolide molecule. The transformation of digoxin to a bufodienolide compound was also reported [Pettit G. R., et al., ibid.]. In the early 1970, it was already established that for a biologically active cardiolide the C/D cis ring junction, the 17.beta.-butenolide moiety and the 3.beta., 14.beta.-dihydroxy are the main prerequisites. The A/B ring junction can be cis and trans without a dramatic change of activity [N. Almirante, et al., Synthetic Letters, 22:1234-1236 (1998)]. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Cardiotonic composition Inventor(s): Dharmadhikari, Nitin Bhalachandra; (Maharashtra, IN), Dhavse, Vaishali Vijay; (Maharashtra, IN) Correspondence: Armstrong, Kratz, Quintos, Hanson & Brooks, Llp; 1725 K Street, NW; Suite 1000; Washington; DC; 20006; US Patent Application Number: 20040048809 Date filed: April 30, 2003 Abstract: The present invention discloses a cardiotonic composition comprising micronized digoxin, hydrophilic polymer(s) and optionally pharmaceutically acceptable excipient(s) in the form of a tablet that releases not more than 50% digoxin in 5 minutes and at least 85% digoxin in 60 minutes. Excerpt(s): The present invention relates to a cardiotonic composition. More specifically, the present invention relates to a cardiotonic composition that releases digoxin reproducibly at a specified rate over a duration of 1 hour. Digoxin, one of the cardiac (or digitalis) glycosides, is known for use in the treatment of congestive heart failure. When administered at the proper therapeutic dosage level, digoxin exerts a direct cardiotonic effect on the myocardium to increase the force of contraction and improve cardiac tone. It has a narrow therapeutic index, i.e. the dose producing the toxic or other undesirable side effects is not much greater than the therapeutically effective dose. Several side effects encountered in the treatment with cardiac glycosides are related to a peak in plasma concentration often occurring a few hours after administration of a dose. Very rapid initial rate of release results in higher peak plasma levels and therefore more side effects. On the other hand, if digoxin is released too slowly from tablets into gastrointestinal fluids then incomplete absorption occurs. The United States Pharmacopoeia [USP XXIV & NF XIX (The United States Pharmacopoeia Convention, Inc., Rockville, Md. 1999)] sets a specification for digoxin tablets requiring that at least 85% digoxin be released in 60 minutes. German Patent DE 1467788 discloses compositions that contain digoxin in solution, sodium alginate and polyacryahnide for gradual and controlled release of digoxin. The patent relates to a liquid composition and does not teach or disclose the preparation of a tablet dosage form providing the desired release profile of the present invention. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Method for controlling preeclampsia and eclampsia Inventor(s): Adair, Charles David; (Signal Mountain, TN) Correspondence: Husch & Eppenberger, Llc; 190 Carondelet Plaza; Suite 600; ST. Louis; MO; 63105-3441; US Patent Application Number: 20040018201 Date filed: July 25, 2002 Abstract: A method of controlling preeclampsia includes the steps of providing a supply of digoxin immune Fab (ovine), calculating an appropriate dosage of the digoxin immune Fab (ovine) based on a patient's weight and using an assumed endogenous digitalis-like factor level, administering the appropriate dosage as an intravenous bolus, and repeating the administration of the appropriate dosage on a fixed schedule. Excerpt(s): The present invention relates generally to the field of medicine and, more particularly, to a method of controlling preeclampsia and eclampsia. Preeclampsia is a rapidly progressive condition occurring during pregnancy characterized by high blood pressure, swelling and protein in the urine. It is specifically defined as the presence of hypertension or pregnancy-induced hypertension ("PIH") accompanied by proteinuria, edema, or both after 20 weeks gestation. Preeclampsia occurs in 5 to 10 percent of all pregnancies and is most common in first-time pregnancies or in first pregnancies with a new partner or husband. Typically, preeclampsia occurs in the late second or third trimesters of pregnancy. Complications of preeclampsia include eclamptic seizures, hemolysis, elevated liver function tests, low platelet count (HELLP) syndrome, hepatic rupture, DIC pulmonary edema, acute renal failure, placental abruption, intrauterine fetal demise (IUFD), cerebral hemorrhage, cortical blindness, and retinal detachment. Preeclampsia causes vasospasm, which constricts and damages the smooth lining of the blood vessels. This leads to the accumulation of platelets in the damaged blood vessels, which form small clots along the blood vessel wall and further narrow the blood vessel. This damage to blood vessels can also lead to edema, including cerebral edema. Vasospasm can occur throughout the body, damaging the heart, kidneys and liver. Vasospasm can also develop in the placenta, decreasing the blood supply to the fetus. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Method of treatment for decreasing mortality resulting from congestive heat failure Inventor(s): Lukas-Laskey, Mary Ann; (Philadelphia, PA), Ruffolo, Robert JR.; (Spring City, PA), Shusterman, Neil Howard; (Wynnewood, PA), Sponer, Gisbert; (Laudenbach, DE), Strein, Klaus; (Hemsbach, DE) Correspondence: Smithkline Beecham Corporation; Corporate Intellectual Property Uw2220; P.O. Box 1539; King OF Prussia; PA; 19406-0939; US Patent Application Number: 20010044455 Date filed: May 23, 2001 Abstract: A method of treatment using a compound of Formula I: 1wherein:R.sub.1 is hydrogen, lower alkanoyl of up to 6 carbon atoms or aroyl selected from benzoyl and naphthoyl;R.sub.2 is hydrogen, lower alkyl of up to 6 carbon atoms or arylalkyl selected from benzyl, phenylethyl and phenylpropyl;R.sub.3 is hydrogen or lower alkyl of up to 6 carbon atoms;R.sub.4 is hydrogen or lower alkyl of up to 6 carbon atoms, or when X is oxygen, R.sub.4 together with R.sub.5 can represent --CH.sub.2--O--;X is a valency bond,

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--CH.sub.2, oxygen or sulfur;Ar is selected from phenyl, naphthyl, indanyl and tetrahydronaphthyl;R.sub.5 and R.sub.6 are individually selected from hydrogen, fluorine, chlorine, bromine, hydroxyl, lower alkyl of up to 6 carbon atoms, a -CONH.sub.2-- group, lower alkoxy of up to 6 carbon atoms, benzyloxy, lower alkylthio of up to 6 carbon atoms, lower alkysulphinyl of up to 6 carbon atoms and lower alkylsulphonyl of up to 6 carbon atoms; orR.sub.5 and R.sub.6 together represent methylenedioxy; or a pharmaceutically acceptable salt thereof, alone or in conjunction with one or more other therapeutic agents, said agents being selected from the group consisting of ACE inhibitors, diuretics, and digoxin for decreasing mortality resulting from congestive heart failure (CHF) in mammals, particularly humans. Excerpt(s): The present invention relates to a new method of treatment using compounds which are dual non-selective.beta.-adrenoceptor and.beta.sub.1adrenoceptor antagonists, in particular the carbazolyl-(4)-oxypropanolamine compounds of Formula I, preferably carvedilol, for decreasing the mortality of patients suffering from congestive heart failure (CHF). The invention also relates to a method of treatment using compounds which are dual non-selective.beta.-adrenoceptor and.alpha.sub.1-adrenoceptor antagonists, in particular the carbazolyl-(4)oxypropanolamine compounds of Formula I, preferably carvedilol, in conjunction with one or more other therapeutic agents, said agents being selected from the group consisting of angiotensin converting enzyme (ACE) inhibitors, diuretics, and digoxin, for decreasing the mortality of patients suffering from CHF. Congestive heart failure occurs as a result of impaired pumping capability of the heart and is associated with abnormal retention of water and sodium. Traditionally, treatment of chronic mild failure has included limitation of physical activity, restriction of salt intake, and the use of a diuretic. If these measures are not sufficient, digoxin, which is an agent that increases the force of mycardial contraction, is typically added to the treatment regiment. Subsequently, angiotensin converting enzyme inhibitors, which are compounds that prevent the conversion of angiotensin I into the pressor-active angiotensin II, are prescribed for chronic treatment of congestive heart failure, in conjunction with a diuretic, digoxin, or both. Congestive heart failure is a condition that is associated with activation of both the renin-angiotensin system (RAS) and the sympathetic nervous system (SNS). Modulation of the RAS by angiotensin converting enzyme inhibitors has been shown to improve the symptoms associated with CHF. Sharpe, D. N., Murphy, J., Coxon, R. & Hannan S. F. (1984) Circulation, 70, 271-278. However, ACE inhibitors appear to have little effect on the enhanced SNS in CHF. Cohn, J. N., Johnson, G. & Ziesche, S., (1991) N. Engl. J. Med., 325, 293-302 and Francis, G. S., Rector, T. S. & Cohn, J. N. (1988) Am. Heart J., 116, 1464-1468. Therefore, there is a need for an agent that would be effective in blocking the activation of the SNS in CHF patients. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Novel formulations of digitalis glycosides for treating cell-proliferative and other diseases Inventor(s): Singh, Chandra U.; (San Antonio, TX) Correspondence: Daniel S. Hodgins; Suite 2100; 112 East Pecan Street; San Antonio; TX; 78205; US Patent Application Number: 20040082521 Date filed: March 31, 2003

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Abstract: The present invention provides methods, preparations, and uses of a variety of liposomal-digitalis glycoside compositions. The present invention also provides proteinstabilized nanoparticle formulations containing liposomal-digitalis glycosides such as Oleandrin, digitoxin, and digoxin with reduced toxicity, high drug to lipid ratio, long circulating time in the bloodstream and the ability to deliver the drug to tumor sites. In another aspect, the present invention provides an effective method to reduce the growth of cancers or reduce the incidence of metastases. Excerpt(s): The present invention is generally directed to the fields of medicine and pharmacology and is specifically related to a pharmaceutical compositions, containing Oleandrin derived from the plant Nerium Oleander L. and other cardiac glycosides, for use in the treatment of the cell-proliferative diseases including cancer, AIDS and other diseases such as diabetes and cardiac disorders. In another aspect, the present invention provides method, preparation and use of a variety of protein microspheres, liposomal and protein stabilized liposomal formulations of Oleandrin and cardiac glycosides with reduced toxicity, high drug to lipid ratio, long-circulating time in the bloodstream and able to deliver the drug to the desired sites such as tumor sites. The present invention also provides an effective method to reduce the growth of cancers or reducing the incidence of metastases. Nerium Oleander is an evergreen shrub reaching four meters in height. Leaves are 10 to 22 cm long, narrow, untoothed and short-stalked, dark or greygreen in color. Some cultivars have leaves variegated with white or yellow. All leaves have a prominent mid rib, are "leathery" in texture and usually arise in groups of three from the stem. The plant produces terminal flower heads, usually pink or white, however, 400 cultivars have been bred and these display a wide variety of different flower color: deep to pale pink, lilac, carmine, purple, salmon, apricot, copper, orange and white (Huxley 1992). Each flower is about 5 cm in diameter and five-petalled. The throat of each flower is fringed with long petal-like projections. Occasionally double flowers are encountered amongst cultivars. The fruit consists of a long narrow capsule 10 to 12 cm long and 6 to 8 mm in diameter; they open to disperse fluffy seeds. Fruiting is uncommon in cultivated plants. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Triple therapy of angiotensin converting enzyme inhibitor epoxy-steroidal aldosterone antagonist and diuretic or digoxin for treatment of cardiovascular disease Inventor(s): Alexander, John C.; (Princeton, NJ), Desai, Subhash; (Wilmette, IL), Roniker, Barbara; (Chicago, IL) Correspondence: Pharmacia Corporation; Corporate Patent Department; P.O. Box 1027; Chesterfield; MO; 63006; US Patent Application Number: 20040077611 Date filed: May 19, 2003 Abstract: Combinations of an ACE inhibitor and an epoxy-steroidal aldosterone receptor antagonist are described for use in treatment of circulatory disorders. Of particular interest are therapies using epoxy-steroidal-type aldosterone receptor antagonist compounds, such as eplerenone, in combination with an angiotensin converting enzyme inhibitor. This co-therapy would be particularly useful to treat congestive heart failure while avoiding or reducing aldosterone-antagonist-induced side effects such as hyperkalemia.

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Excerpt(s): This application claims priority of U.S. provisional application Ser. No. 60/122,997 filed Mar. 05, 1999 and U.S. provisional application Ser. No. 60/122,998 filed Mar. 05, 1999. Combinations of an angiotensin converting enzyme inhibitor and an epoxy-steroidal aldosterone receptor antagonist are described for use in treatment of circulatory disorders, including cardiovascular diseases such as heart failure, hypertension and congestive heart failure. Of particular interest are therapies using epoxy-steroidal-type aldosterone receptor antagonist compound eplerenone in combination with an angiotensin converting enzyme inhibitor. Myocardial (or cardiac) failure, whether a consequence of previous myocardial infarction(s), heart disease associated with hypertension, or primary cardiomyopathy, is a major health problem of worldwide proportions. The incidence of symptomatic heart failure has risen steadily over the past several decades. 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 digoxin, 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 “digoxin” (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 digoxin. You can also use this procedure to view pending patent applications concerning digoxin. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

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CHAPTER 6. BOOKS ON DIGOXIN Overview This chapter provides bibliographic book references relating to digoxin. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on digoxin include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.

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 area, simply type “digoxin” (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:10 •

Digitoxin and digoxin in serum: a review with special reference to the binding of digitoxin and digoxin to the serum proteins. Author: by Axel Brock; Year: 1976

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Digitoxin und Digoxin: eine Darstellung des aktuellen Wissenstandes. Author: KnutOlaf Haustein; Year: 1996

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Factors of importance for valid digitalis assays particularly for the determination of digoxin in plasma and urine. Author: Lilian Molin; Year: 1986

10

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

Drug Monitoring Source: in Catto, G.R.D. New Clinical Applications-Nephrology: Drugs and the Kidney. Hingham, MA: Kluwer Academic Publishers. p. 113-151. 1990. Contact: Available from Kluwer Academic Publishers. P.O. Box 358, Accord Station, Hingham, MA 02018-0358. (617) 871-6600. PRICE: $54. ISBN: 0792389182. Summary: This review aims to cover aspects of drug monitoring with particular emphasis on the problems in patients with renal disease. Since an understanding of therapeutic drug monitoring requires a basic knowledge of drug disposition and pharmacokinetics, some important aspects of these topics are discussed first. Following consideration of therapeutic drug concentration monitoring, the final section of this review briefly discusses aspects of monitoring drugs by use of measurable pharmacodynamic end points. Topics include: the effect of renal disease on drug disposition and pharmacokinetics (absorption and bioavailability, distribution and protein binding, metabolism, excretion); the effect of renal disease on drug pharmacodynamics; and therapeutic drug monitoring (assay methods, individual drugs (digoxin, gentamicin, lithium, anticonvulsant drugs (phenytoin, carbamazepine, sodium valproate, other anticonvulsants), theophylline, cyclosporin), drug overdose, compliance with drug therapy, cost-effectiveness, pharmacodynamics). It is concluded that therapeutic drug monitoring has a limited, though important, role to play in the overall strategy for drug use in renal disease, and that, for a small number of drugs, such monitoring is essential to help minimize problems of both sub-therapeutic dosing and adverse effects. 33 references.

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CHAPTER 7. PERIODICALS AND NEWS ON DIGOXIN Overview In this chapter, we suggest a number of news sources and present various periodicals that cover digoxin.

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

Protherics reports FDA approval for antidote to digoxin toxicity Source: Reuters Industry Breifing Date: September 18, 2001

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FDA contends Jerome Stevens' Digoxin formulation change was not validated Source: Reuters Industry Breifing Date: September 26, 2000

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Incidence of digoxin toxicity on the decline Source: Reuters Medical News Date: December 17, 1998

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IV propafenone superior to IV digoxin for termination of atrial fibrillation Source: Reuters Medical News Date: September 07, 1998

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Impact of St. John's wort on digoxin levels may vary Source: Reuters Industry Breifing Date: June 30, 2004

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Carvedilol plus digoxin better than either alone in heart failure with atrial fib Source: Reuters Industry Breifing Date: December 24, 2003

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Colour vision deficiency can occur with therapeutic levels of digoxin in elderly Source: Reuters Medical News Date: November 05, 2002

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Long-term Digoxin Therapy Indicated For Subset Of Heart Failure Patients Source: Reuters Medical News Date: March 19, 1998

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Mild Heart Failure Worsens Upon Digoxin Withdrawal Source: Reuters Medical News Date: July 08, 1997

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Low-Dose And Moderate-Dose Digoxin Comparable In Patients With Mild To Moderate CHF Source: Reuters Medical News Date: May 09, 1997

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Debate Over Digoxin Use For Atrial Fibrillation Continues Source: Reuters Medical News Date: April 28, 1997

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Toad-Venom Toxicity Is Treatable With Digoxin Fab Fragments Source: Reuters Medical News Date: November 19, 1996

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Safety Of Digoxin For Heart Failure Patients In Sinus Rhythm Questioned Source: Reuters Medical News Date: August 02, 1996

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Short-Term Effects Of Digoxin On Autonomic Function In CHF Patients Sustained With Long-Term Administration Source: Reuters Medical News Date: February 08, 1995 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

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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 “digoxin” (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 “digoxin” (or synonyms). If you know the name of a company that is relevant to digoxin, 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 “digoxin” (or synonyms).

Academic Periodicals covering Digoxin Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to digoxin. In addition to these sources, you can search for articles covering digoxin 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.”

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If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”

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CHAPTER 8. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.

U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for digoxin. 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 digoxin. 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 digoxin: Digitalis Medicines •

Systemic - U.S. Brands: Lanoxicaps; Lanoxin; Lanoxin Elixir Pediatric; Lanoxin Injection; Lanoxin Injection Pediatric http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202194.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. If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.

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APPENDICES

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

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

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

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

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

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

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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

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

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

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

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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

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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

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

12

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

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•

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

•

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

The NLM Gateway14 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.15 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “digoxin” (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 14209 58 998 15 75 15355

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

14

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

15

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

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

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

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

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

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

•

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

19 Adapted 20

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

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

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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on digoxin 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 digoxin. 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 digoxin. 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 “digoxin”:

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Arrhythmia http://www.nlm.nih.gov/medlineplus/arrhythmia.html Cardiomyopathy http://www.nlm.nih.gov/medlineplus/cardiomyopathy.html Congenital Heart Disease http://www.nlm.nih.gov/medlineplus/congenitalheartdisease.html Epilepsy http://www.nlm.nih.gov/medlineplus/epilepsy.html Heart Diseases http://www.nlm.nih.gov/medlineplus/heartdiseases.html Heart Failure http://www.nlm.nih.gov/medlineplus/heartfailure.html You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The NIH Search Utility The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to digoxin. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats

•

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

•

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

•

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

•

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

•

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

Patient Resources

•

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

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

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The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “digoxin” (or a synonym) into the search box, and click “Submit Query.”

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

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

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

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

22

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

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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)23: •

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

•

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

•

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

•

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

•

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

•

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

•

California: Gateway Health Library (Sutter Gould Medical Foundation)

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

23

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

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•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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

•

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

•

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

•

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

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

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

•

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

•

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

•

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

•

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

•

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

•

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

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

Basic Guidelines for Digoxin Digitoxin - test Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003577.htm Digoxin - test Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003568.htm

•

Signs & Symptoms for Digoxin Fainting Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003092.htm

•

Diagnostics and Tests for Digoxin Blood pressure Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003398.htm Therapeutic drug monitoring Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003430.htm

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Venipuncture Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003423.htm •

Background Topics for Digoxin Adolescent test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002054.htm Bleeding Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000045.htm Infant test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002055.htm Preschooler test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002057.htm Schoolage test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002058.htm Toddler test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002056.htm

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

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

•

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

•

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

•

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

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DIGOXIN DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Absolute risk: The observed or calculated probability of an event in a population under study, as contrasted with the relative risk. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] 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] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Actin: Essential component of the cell skeleton. [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] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenal Glands: Paired glands situated in the retroperitoneal tissues at the superior pole of each kidney. [NIH] 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] Adsorption: The condensation of gases, liquids, or dissolved substances on the surfaces of solids. It includes adsorptive phenomena of bacteria and viruses as well as of tissues treated with exogenous drugs and chemicals. [NIH] Adsorptive: It captures volatile compounds by binding them to agents such as activated carbon or adsorptive resins. [NIH] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [EU]

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Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Age of Onset: The age or period of life at which a disease or the initial symptoms or manifestations of a disease appear in an individual. [NIH] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] 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] Aldosterone: (11 beta)-11,21-Dihydroxy-3,20-dioxopregn-4-en-18-al. A hormone secreted by the adrenal cortex that functions in the regulation of electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. [NIH] 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] 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] 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] Aluminum: A metallic element that has the atomic number 13, atomic symbol Al, and atomic weight 26.98. [NIH] Ambulatory Care: Health care services provided to patients on an ambulatory basis, rather than by admission to a hospital or other health care facility. The services may be a part of a hospital, augmenting its inpatient services, or may be provided at a free-standing facility. [NIH]

Amine: An organic compound containing nitrogen; any member of a group of chemical

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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] Amlodipine: 2-((2-Aminoethoxy)methyl)-4-(2-chlorophenyl)-1,4-dihydro-6-methyl-3,5pyridinedicarboxylic acid 3-ethyl 5-methyl ester. A long-acting dihydropyridine calcium channel blocker. It is effective in the treatment of angina pectoris and hypertension. [NIH] Amnestic: Nominal aphasia; a difficulty in finding the right name for an object. [NIH] Amnion: The extraembryonic membrane which contains the embryo and amniotic fluid. [NIH]

Amniotic Fluid: Amniotic cavity fluid which is produced by the amnion and fetal lungs and kidneys. [NIH] Amoxicillin: A broad-spectrum semisynthetic antibiotic similar to ampicillin except that its resistance to gastric acid permits higher serum levels with oral administration. [NIH] Amphetamine: A powerful central nervous system stimulant and sympathomimetic. Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. Amphetamine is also a drug of abuse and a psychotomimetic. The l- and the d,l-forms are included here. The l-form has less central nervous system activity but stronger cardiovascular effects. The d-form is dextroamphetamine. [NIH] 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] Amyloidosis: A group of diseases in which protein is deposited in specific organs (localized amyloidosis) or throughout the body (systemic amyloidosis). Amyloidosis may be either primary (with no known cause) or secondary (caused by another disease, including some types of cancer). Generally, primary amyloidosis affects the nerves, skin, tongue, joints, heart, and liver; secondary amyloidosis often affects the spleen, kidneys, liver, and adrenal glands. [NIH]

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Anaerobic: 1. Lacking molecular oxygen. 2. Growing, living, or occurring in the absence of molecular oxygen; pertaining to an anaerobe. [EU] 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] 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]

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] Aneurysm: A sac formed by the dilatation of the wall of an artery, a vein, or the heart. [NIH] Angina: Chest pain that originates in the heart. [NIH] Angina Pectoris: The symptom of paroxysmal pain consequent to myocardial ischemia usually of distinctive character, location and radiation, and provoked by a transient stressful situation during which the oxygen requirements of the myocardium exceed the capacity of the coronary circulation to supply it. [NIH] Anginal: Pertaining to or characteristic of angina. [EU] 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] Angiotensin converting enzyme inhibitor: A drug used to decrease pressure inside blood vessels. [NIH] Angiotensin-Converting Enzyme Inhibitors: A class of drugs whose main indications are the treatment of hypertension and heart failure. They exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility. [NIH] Angiotensinogen: An alpha-globulin of which a fragment of 14 amino acids is converted by renin to angiotensin I, the inactive precursor of angiotensin II. It is a member of the serpin superfamily. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test

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new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Anisotropy: A physical property showing different values in relation to the direction in or along which the measurement is made. The physical property may be with regard to thermal or electric conductivity or light refraction. In crystallography, it describes crystals whose index of refraction varies with the direction of the incident light. It is also called acolotropy and colotropy. The opposite of anisotropy is isotropy wherein the same values characterize the object when measured along axes in all directions. [NIH] Ankle: That part of the lower limb directly above the foot. [NIH] Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Anthelmintic: An agent that is destructive to worms. [EU] Antianginal: Counteracting angina or anginal conditions. [EU] Anti-Arrhythmia Agents: Agents used for the treatment or prevention of cardiac arrhythmias. They may affect the polarization-repolarization phase of the action potential, its excitability or refractoriness, or impulse conduction or membrane responsiveness within cardiac fibers. Anti-arrhythmia agents are often classed into four main groups according to their mechanism of action: sodium channel blockade, beta-adrenergic blockade, repolarization prolongation, or calcium channel blockade. [NIH] Antiarrhythmic: An agent that prevents or alleviates cardiac arrhythmia. [EU] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Antibody Specificity: The property of antibodies which enables them to react with some antigenic determinants and not with others. Specificity is dependent on chemical composition, physical forces, and molecular structure at the binding site. [NIH] Anticholinergic: An agent that blocks the parasympathetic nerves. Called also parasympatholytic. [EU] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Anticonvulsant: An agent that prevents or relieves convulsions. [EU] Antidepressant: A drug used to treat depression. [NIH] Antidote: A remedy for counteracting a poison. [EU] Antiepileptic: An agent that combats epilepsy. [EU]

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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 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] Antihypertensive: An agent that reduces high blood pressure. [EU] Anti-inflammatory: Having to do with reducing inflammation. [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] Antineoplastic Agents: Substances that inhibit or prevent the proliferation of neoplasms. [NIH]

Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antipyretic: An agent that relieves or reduces fever. Called also antifebrile, antithermic and febrifuge. [EU] Antivirals: Drugs used to treat infections caused by viruses. [NIH] Anuria: Inability to form or excrete urine. [NIH] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Anxiolytic: An anxiolytic or antianxiety agent. [EU] Aorta: The main trunk of the systemic arteries. [NIH] Aphakia: Absence of crystalline lens totally or partially from field of vision, from any cause except after cataract extraction. Aphakia is mainly congenital or as result of lens dislocation and subluxation. [NIH] Aqueous: Having to do with water. [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Arrhythmogenic: Producing or promoting arrhythmia. [EU] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arteriolar: Pertaining to or resembling arterioles. [EU] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteriovenous: Both arterial and venous; pertaining to or affecting an artery and a vein. [EU] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH]

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Ascorbic Acid: A six carbon compound related to glucose. It is found naturally in citrus fruits and many vegetables. Ascorbic acid is an essential nutrient in human diets, and necessary to maintain connective tissue and bone. Its biologically active form, vitamin C, functions as a reducing agent and coenzyme in several metabolic pathways. Vitamin C is considered an antioxidant. [NIH] Aspergillosis: Infections with fungi of the genus Aspergillus. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Asymptomatic: Having no signs or symptoms of disease. [NIH] Atrial: Pertaining to an atrium. [EU] Atrial Fibrillation: Disorder of cardiac rhythm characterized by rapid, irregular atrial impulses and ineffective atrial contractions. [NIH] Atrial Flutter: Rapid, irregular atrial contractions due to an abnormality of atrial excitation. [NIH]

Atrial Function: The hemodynamic and electrophysiological action of the atria. [NIH] Atrioventricular: Pertaining to an atrium of the heart and to a ventricle. [EU] Atrioventricular Node: A small nodular mass of specialized muscle fibers located in the interatrial septum near the opening of the coronary sinus. It gives rise to the atrioventricular bundle of the conduction system of the heart. [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] Attenuated: Strain with weakened or reduced virulence. [NIH] Autodigestion: Autolysis; a condition found in disease of the stomach: the stomach wall is digested by the gastric juice. [NIH] Autonomic Nervous System: The enteric, parasympathetic, and sympathetic nervous systems taken together. Generally speaking, the autonomic nervous system regulates the internal environment during both peaceful activity and physical or emotional stress. Autonomic activity is controlled and integrated by the central nervous system, especially the hypothalamus and the solitary nucleus, which receive information relayed from visceral afferents; these and related central and sensory structures are sometimes (but not here) considered to be part of the autonomic nervous system itself. [NIH] Autopsy: Postmortem examination of the body. [NIH] Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [NIH] Azithromycin: A semi-synthetic macrolide antibiotic structurally related to erythromycin. It has been used in the treatment of Mycobacterium avium intracellulare infections, toxoplasmosis, and cryptosporidiosis. [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] Bacteriostatic: 1. Inhibiting the growth or multiplication of bacteria. 2. An agent that inhibits the growth or multiplication of bacteria. [EU] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located

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in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [NIH] 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] Basophil: A type of white blood cell. Basophils are granulocytes. [NIH] Berberine: An alkaloid from Hydrastis canadensis L., Berberidaceae. It is also found in many other plants. It is relatively toxic parenterally, but has been used orally for various parasitic and fungal infections and as antidiarrheal. [NIH] Beta blocker: A drug used to slow the heart rate and reduce pressure inside blood vessels. It also can regulate heart rhythm. [NIH] Beta-pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bile Acids and Salts: Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones. [NIH] Bile duct: A tube through which bile passes in and out of the liver. [NIH] 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 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] Bioluminescence: The emission of light by living organisms such as the firefly, certain mollusks, beetles, fish, bacteria, fungi and protozoa. [NIH] Bioreactors: Tools or devices for generating products using the synthetic or chemical conversion capacity of a biological system. They can be classical fermentors, cell culture perfusion systems, or enzyme bioreactors. For production of proteins or enzymes, recombinant microorganisms such as bacteria, mammalian cells, or insect or plant cells are usually chosen. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU]

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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 nonsynthetic (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] Blastocyst: The mammalian embryo in the post-morula stage in which a fluid-filled cavity, enclosed primarily by trophoblast, contains an inner cell mass which becomes the embryonic disc. [NIH] Blastomycosis: A fungal infection that may appear in two forms: 1) a primary lesion characterized by the formation of a small cutaneous nodule and small nodules along the lymphatics that may heal within several months; and 2) chronic granulomatous lesions characterized by thick crusts, warty growths, and unusual vascularity and infection in the middle or upper lobes of the lung. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blood-Brain Barrier: Specialized non-fenestrated tightly-joined endothelial cells (tight junctions) that form a transport barrier for certain substances between the cerebral capillaries and the brain tissue. [NIH] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]

Body Fluids: Liquid components of living organisms. [NIH] Bolus: A single dose of drug usually injected into a blood vessel over a short period of time. Also called bolus infusion. [NIH] Bolus infusion: A single dose of drug usually injected into a blood vessel over a short period of time. Also called bolus. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion.

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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] Bradycardia: Excessive slowness in the action of the heart, usually with a heart rate below 60 beats per minute. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] 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] Bronchitis: Inflammation (swelling and reddening) of the bronchi. [NIH] Bupivacaine: A widely used local anesthetic agent. [NIH] Bypass: A surgical procedure in which the doctor creates a new pathway for the flow of body fluids. [NIH] Cachexia: General ill health, malnutrition, and weight loss, usually associated with chronic disease. [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] 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 Blockers: A class of drugs that act by selective inhibition of calcium influx through cell membranes or on the release and binding of calcium in intracellular pools. Since they are inducers of vascular and other smooth muscle relaxation, they are used in the drug therapy of hypertension and cerebrovascular spasms, as myocardial protective agents, and in the relaxation of uterine spasms. [NIH] Canrenone: A synthetic pregnadiene compound with anti-aldosterone activity. [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]

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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] Carbamazepine: An anticonvulsant used to control grand mal and psychomotor or focal seizures. Its mode of action is not fully understood, but some of its actions resemble those of phenytoin; although there is little chemical resemblance between the two compounds, their three-dimensional structure is similar. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carboxy: Cannabinoid. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]

Cardenolides: C(23)-steroids with methyl groups at C-10 and C-13 and a five-membered lactone at C-17. They are aglycone constituents of cardiac glycosides and must have at least one double bond in the molecule. the class includes cardadienolides and cardatrienolides. Members include digitoxin and digoxin and their derivatives and the strophanthins. [NIH] Cardiac: Having to do with the heart. [NIH] Cardiac arrest: A sudden stop of heart function. [NIH] Cardiac Glycosides: Substances obtained from species of Digitalis, Strophanthus, and other plants that contain specific steroid glycosides or their semisynthetic derivatives and used in congestive heart failure. They increase the force of cardiac contraction without significantly affecting other parameters, but are very toxic at larger doses. Their mechanism of action usually involves inhibition of the Na(+)-K(+)-exchanging ATPase and they are often used in cell biological studies for that purpose. [NIH] Cardiac Output: The volume of blood passing through the heart per unit of time. It is usually expressed as liters (volume) per minute so as not to be confused with stroke volume (volume per beat). [NIH] Cardiogenic: Originating in the heart; caused by abnormal function of the heart. [EU] Cardiomyopathy: A general diagnostic term designating primary myocardial disease, often of obscure or unknown etiology. [EU] Cardiopulmonary: Having to do with the heart and lungs. [NIH] Cardiopulmonary Bypass: Diversion of the flow of blood from the entrance of the right atrium directly to the aorta (or femoral artery) via an oxygenator thus bypassing both the heart and lungs. [NIH] Cardiorespiratory: Relating to the heart and lungs and their function. [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]

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Cardiotonic Agents: Agents that have a tonic effect on the heart or increase cardiac output. They may be glycosidic steroids related to Digitalis products, sympathomimetics, or other drugs and are used after myocardial infarcts, cardiac surgery, in shock, or in congestive heart failure. [NIH] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Cardioversion: Electrical reversion of cardiac arrhythmias to normal sinus rhythm, formerly using alternatic current, but now employing direct current. [NIH] Carmine: Coloring matter from the insect Coccus cacti L. It is used in foods, pharmaceuticals, toiletries, etc., as a dye, and also has use as a microscopic stain and biological marker. [NIH] Carotene: The general name for a group of pigments found in green, yellow, and leafy vegetables, and yellow fruits. The pigments are fat-soluble, unsaturated aliphatic hydrocarbons functioning as provitamins and are converted to vitamin A through enzymatic processes in the intestinal wall. [NIH] 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] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] Causal: Pertaining to a cause; directed against a cause. [EU] Caustic: An escharotic or corrosive agent. Called also cauterant. [EU] 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 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] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Cephalexin: A semisynthetic cephalosporin antibiotic with antimicrobial activity similar to that of cephaloridine or cephalothin, but somewhat less potent. It is effective against both gram-positive and gram-negative organisms. [NIH] Cephaloridine: A cephalosporin antibiotic. [NIH]

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Cephalothin: A cephalosporin antibiotic. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Cortex: The thin layer of gray matter on the surface of the cerebral hemisphere that develops from the telencephalon and folds into gyri. It reaches its highest development in man and is responsible for intellectual faculties and higher mental functions. [NIH] Cerebral Hemorrhage: Bleeding into a cerebral hemisphere of the brain, including lobar, subcortical white matter, and basal ganglia hemorrhages. Commonly associated conditions include hypertension; intracranial arteriosclerosis; intracranial aneurysm; craniocerebral trauma; intracranial arteriovenous malformations; cerebral amyloid angiopathy; and cerebral infarction. [NIH] Cerebral Infarction: The formation of an area of necrosis in the cerebrum caused by an insufficiency of arterial or venous blood flow. Infarcts of the cerebrum are generally classified by hemisphere (i.e., left vs. right), lobe (e.g., frontal lobe infarction), arterial distribution (e.g., infarction, anterior cerebral artery), and etiology (e.g., embolic infarction). [NIH]

Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Chin: The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. [NIH] 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] 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] Cholinesterase Inhibitors: Drugs that inhibit cholinesterases. The neurotransmitter acetylcholine is rapidly hydrolyzed, and thereby inactivated, by cholinesterases. When cholinesterases are inhibited, the action of endogenously released acetylcholine at cholinergic synapses is potentiated. Cholinesterase inhibitors are widely used clinically for their potentiation of cholinergic inputs to the gastrointestinal tract and urinary bladder, the eye, and skeletal muscles; they are also used for their effects on the heart and the central nervous system. [NIH] Chorea: Involuntary, forcible, rapid, jerky movements that may be subtle or become confluent, markedly altering normal patterns of movement. Hypotonia and pendular reflexes are often associated. Conditions which feature recurrent or persistent episodes of chorea as a primary manifestation of disease are referred to as choreatic disorders. Chorea is also a frequent manifestation of basal ganglia diseases. [NIH] Choreatic Disorders: Acquired and hereditary conditions which feature chorea as a primary

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manifestation of the disease process. [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 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] Chymopapain: A cysteine endopeptidase isolated from papaya latex. Preferential cleavage at glutamic and aspartic acid residues. EC 3.4.22.6. [NIH] Circulatory system: The system that contains the heart and the blood vessels and moves blood throughout the body. This system helps tissues get enough oxygen and nutrients, and it helps them get rid of waste products. The lymph system, which connects with the blood system, is often considered part of the circulatory system. [NIH] Cirrhosis: A type of chronic, progressive liver disease. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Citalopram: A selective neuronal serotonin reuptake inhibitor and a clinically effective antidepressant with tolerable side effects. The drug is also effective in reducing ethanol uptake in alcoholics and is used in depressed patients who also suffer from tardive dyskinesia (TD) in preference to tricyclic antidepressants, which aggravate this condition. [NIH]

Clarithromycin: A semisynthetic macrolide antibiotic derived from erythromycin that is active against a variety of microorganisms. It can inhibit protein synthesis in bacteria by reversibly binding to the 50S ribosomal subunits. This inhibits the translocation of aminoacyl transfer-RNA and prevents peptide chain elongation. [NIH] Clear cell carcinoma: A rare type of tumor of the female genital tract in which the inside of the cells looks clear when viewed under a microscope. [NIH] 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] 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]

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Codeine: An opioid analgesic related to morphine but with less potent analgesic properties and mild sedative effects. It also acts centrally to suppress cough. [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] Colitis: Inflammation of the colon. [NIH] Colloidal: Of the nature of a colloid. [EU] Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus. [NIH] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [NIH] 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] Compliance: Distensibility measure of a chamber such as the lungs (lung compliance) or bladder. Compliance is expressed as a change in volume per unit change in pressure. [NIH]

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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] 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] Conduction: The transfer of sound waves, heat, nervous impulses, or electricity. [EU] Cones: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide sharp central vision and color vision. [NIH] 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] Consciousness: Sense of awareness of self and of the environment. [NIH] Constriction: The act of constricting. [NIH] Constriction, Pathologic: The condition of an anatomical structure's being constricted beyond normal dimensions. [NIH] 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] 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] Convulsions: A general term referring to sudden and often violent motor activity of cerebral or brainstem origin. Convulsions may also occur in the absence of an electrical cerebral discharge (e.g., in response to hypotension). [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Cor: The muscular organ that maintains the circulation of the blood. c. adiposum a heart

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that has undergone fatty degeneration or that has an accumulation of fat around it; called also fat or fatty, heart. c. arteriosum the left side of the heart, so called because it contains oxygenated (arterial) blood. c. biloculare a congenital anomaly characterized by failure of formation of the atrial and ventricular septums, the heart having only two chambers, a single atrium and a single ventricle, and a common atrioventricular valve. c. bovinum (L. 'ox heart') a greatly enlarged heart due to a hypertrophied left ventricle; called also c. taurinum and bucardia. c. dextrum (L. 'right heart') the right atrium and ventricle. c. hirsutum, c. villosum. c. mobile (obs.) an abnormally movable heart. c. pendulum a heart so movable that it seems to be hanging by the great blood vessels. c. pseudotriloculare biatriatum a congenital cardiac anomaly in which the heart functions as a three-chambered heart because of tricuspid atresia, the right ventricle being extremely small or rudimentary and the right atrium greatly dilated. Blood passes from the right to the left atrium and thence disease due to pulmonary hypertension secondary to disease of the lung, or its blood vessels, with hypertrophy of the right ventricle. [EU] 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 Arteriosclerosis: Thickening and loss of elasticity of the coronary arteries. [NIH] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Corpus: The body of the uterus. [NIH] Corpus Luteum: The yellow glandular mass formed in the ovary by an ovarian follicle that has ruptured and discharged its ovum. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Cortical Blindness: The inability to understand or interpret what is seen due to a disturbance in the cerebral associational areas, the retina, the sensory pathways, and the striate area being intact. [NIH] 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] Creatine: An amino acid that occurs in vertebrate tissues and in urine. In muscle tissue, creatine generally occurs as phosphocreatine. Creatine is excreted as creatinine in the urine. [NIH]

Creatine Kinase: A transferase that catalyzes formation of phosphocreatine from ATP + creatine. The reaction stores ATP energy as phosphocreatine. Three cytoplasmic isoenzymes have been identified in human tissues: MM from skeletal muscle, MB from myocardial tissue, and BB from nervous tissue as well as a mitochondrial isoenzyme. Macro-creatine kinase refers to creatine kinase complexed with other serum proteins. EC 2.7.3.2. [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] Creatinine clearance: A test that measures how efficiently the kidneys remove creatinine and other wastes from the blood. Low creatinine clearance indicates impaired kidney function. [NIH] Cryptosporidiosis: Parasitic intestinal infection with severe diarrhea caused by a protozoan, Cryptosporidium. It occurs in both animals and humans. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cyclosporine: A drug used to help reduce the risk of rejection of organ and bone marrow transplants by the body. It is also used in clinical trials to make cancer cells more sensitive to anticancer drugs. [NIH] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cystine: A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. [NIH]

Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] 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] Daunorubicin: Very toxic anthracycline aminoglycoside antibiotic isolated from Streptomyces peucetius and others, used in treatment of leukemias and other neoplasms. [NIH]

Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Decidua: The epithelial lining of the endometrium that is formed before the fertilized ovum reaches the uterus. The fertilized ovum embeds in the decidua. If the ovum is not fertilized, the decidua is shed during menstruation. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Demethylation: Process that releases substantial amounts of carbon dioxide in the liver. [NIH]

Dental Caries: Localized destruction of the tooth surface initiated by decalcification of the enamel followed by enzymatic lysis of organic structures and leading to cavity formation. If

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left unchecked, the cavity may penetrate the enamel and dentin and reach the pulp. The three most prominent theories used to explain the etiology of the disase are that acids produced by bacteria lead to decalcification; that micro-organisms destroy the enamel protein; or that keratolytic micro-organisms produce chelates that lead to decalcification. [NIH]

Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Depressive Disorder: An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent. [NIH] DES: Diethylstilbestrol. A synthetic hormone that was prescribed from the early 1940s until 1971 to help women with complications of pregnancy. DES has been linked to an increased risk of clear cell carcinoma of the vagina in daughters of women who used DES. DES may also increase the risk of breast cancer in women who used DES. [NIH] 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] Dexmedetomidine: A selective inhibitor of receptors, adrenergic alpha-2 that has analgesic and sedative properties. Medetomidine is the other racemic form. [NIH] Dextroamphetamine: The d-form of amphetamine. It is a central nervous system stimulant and a sympathomimetic. It has also been used in the treatment of narcolepsy and of attention deficit disorders and hyperactivity in children. Dextroamphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulating release of monamines, and inhibiting monoamine oxidase. It is also a drug of abuse and a psychotomimetic. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] 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] Diastole: Period of relaxation of the heart, especially the ventricles. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Diastolic heart failure: Inability of the heart to relax properly and fill with blood as a result of stiffening of the heart muscle. [NIH] Diethylcarbamazine: An anthelmintic used primarily as the citrate in the treatment of filariasis, particularly infestations with Wucheria bancrofti or Loa loa. [NIH] Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] 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]

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Digitalis Glycosides: Glycosides from plants of the genus Digitalis. Some of these are useful as cardiotonic and anti-arrhythmia agents. Included also are semi-synthetic derivatives of the naturally occurring glycosides. The term has sometimes been used more broadly to include all cardiac glycosides, but here is restricted to those related to Digitalis. [NIH] Digitoxigenin: 3 beta,14-Dihydroxy-5 beta-card-20(22)enolide. A cardenolide which is the aglycon of digitoxin. Synonyms: Cerberigenin; Echujetin; Evonogenin; Thevetigenin. [NIH] Digoxigenin: 3 beta,12 beta,14-Trihydroxy-5 beta-card-20(22)-enolide. A cardenolide which is the aglycon of digoxin. Can be obtained by hydrolysis of digoxin or from Digitalis orientalis L. and Digitalis lanata Ehrh. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Dihydroxy: AMPA/Kainate antagonist. [NIH] Dilatation, Pathologic: The condition of an anatomical structure's being dilated beyond normal dimensions. [NIH] Dilated cardiomyopathy: Heart muscle disease that leads to enlargement of the heart's chambers, robbing the heart of its pumping ability. [NIH] Dilation: A process by which the pupil is temporarily enlarged with special eye drops (mydriatic); allows the eye care specialist to better view the inside of the eye. [NIH] Dilator: A device used to stretch or enlarge an opening. [NIH] Diltiazem: A benzothiazepine derivative with vasodilating action due to its antagonism of the actions of the calcium ion in membrane functions. It is also teratogenic. [NIH] Dilution: A diluted or attenuated medicine; in homeopathy, the diffusion of a given quantity of a medicinal agent in ten or one hundred times the same quantity of water. [NIH] Dimethyl: A volatile metabolite of the amino acid methionine. [NIH] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Dirofilaria: A genus of filarial nematodes. Various immature species have been found to infect the eyes or subcutaneous tissue in humans. [NIH] Dirofilaria immitis: A filarial parasite primarily of dogs but occurring also in foxes, wolves, and humans. The parasite is transmitted by mosquitoes. [NIH] Discrete: Made up of separate parts or characterized by lesions which do not become blended; not running together; separate. [NIH] Disopyramide: Alpha-(2-(Bis(l-methylethyl)amino)ethyl)-alpha-phenyl-2-pyridine acetamide. A class I anti-arrhythmic agent (one that interferes directly with the depolarization of the cardiac membrane and thus serves as a membrane-stabilizing agent) with a depressant action on the heart similar to that of guanidine. It also possesses some anticholinergic and local anesthetic properties. [NIH] Disposition: A tendency either physical or mental toward certain diseases. [EU] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal

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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] Dominance: In genetics, the full phenotypic expression of a gene in both heterozygotes and homozygotes. [EU] Donepezil: A drug used in the treatment of Alzheimer's disease. It belongs to the family of drugs called cholinesterase inhibitors. It is being studied as a treatment for side effects caused by radiation therapy to the brain. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Double-blind: Pertaining to a clinical trial or other experiment in which neither the subject nor the person administering treatment knows which treatment any particular subject is receiving. [EU] Doxorubicin: Antineoplastic antibiotic obtained from Streptomyces peucetics. It is a hydroxy derivative of daunorubicin and is used in treatment of both leukemia and solid tumors. [NIH] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Monitoring: The process of observing, recording, or detecting the effects of a chemical substance administered to an individual therapeutically or diagnostically. [NIH] Duct: A tube through which body fluids pass. [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] Dyskinesia: Impairment of the power of voluntary movement, resulting in fragmentary or incomplete movements. [EU] Eclampsia: Onset of convulsions or coma in a previously diagnosed pre-eclamptic patient. [NIH]

Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH]

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Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Elastic: Susceptible of resisting and recovering from stretching, compression or distortion applied by a force. [EU] Electrocardiogram: Measurement of electrical activity during heartbeats. [NIH] Electrode: Component of the pacing system which is at the distal end of the lead. It is the interface with living cardiac tissue across which the stimulus is transmitted. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] 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]

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] Emphysema: A pathological accumulation of air in tissues or organs. [NIH] Enalapril: An angiotensin-converting enzyme inhibitor that is used to treat hypertension. [NIH]

Enalaprilat: The active metabolite of enalapril and a potent intravenously administered angiotensin-converting enzyme inhibitor. It is an effective agent for the treatment of essential hypertension and has beneficial hemodynamic effects in heart failure. The drug produces renal vasodilation with an increase in sodium excretion. [NIH] Encapsulated: Confined to a specific, localized area and surrounded by a thin layer of tissue. [NIH]

Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endometrium: The layer of tissue that lines the uterus. [NIH] Endoscopic: A technique where a lateral-view endoscope is passed orally to the duodenum for visualization of the ampulla of Vater. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH]

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Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Enhancer: Transcriptional element in the virus genome. [NIH] Enteric-coated: A term designating a special coating applied to tablets or capsules which prevents release and absorption of their contents until they reach the intestines. [EU] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. [NIH] Ephedrine: An alpha- and beta-adrenergic agonist that may also enhance release of norepinephrine. It has been used in the treatment of several disorders including asthma, heart failure, rhinitis, and urinary incontinence, and for its central nervous system stimulatory effects in the treatment of narcolepsy and depression. It has become less extensively used with the advent of more selective agonists. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Epoprostenol: A prostaglandin that is biosynthesized enzymatically from prostaglandin endoperoxides in human vascular tissue. It is a potent inhibitor of platelet aggregation. The sodium salt has been also used to treat primary pulmonary hypertension. [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] Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Ethnic Groups: A group of people with a common cultural heritage that sets them apart from others in a variety of social relationships. [NIH] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Excipient: Any more or less inert substance added to a prescription in order to confer a suitable consistency or form to the drug; a vehicle. [EU]

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Excitability: Property of a cardiac cell whereby, when the cell is depolarized to a critical level (called threshold), the membrane becomes permeable and a regenerative inward current causes an action potential. [NIH] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Excrete: To get rid of waste from the body. [NIH] Exercise Test: Controlled physical activity, more strenuous than at rest, which is performed in order to allow assessment of physiological functions, particularly cardiovascular and pulmonary, but also aerobic capacity. Maximal (most intense) exercise is usually required but submaximal exercise is also used. The intensity of exercise is often graded, using criteria such as rate of work done, oxygen consumption, and heart rate. Physiological data obtained from an exercise test may be used for diagnosis, prognosis, and evaluation of disease severity, and to evaluate therapy. Data may also be used in prescribing exercise by determining a person's exercise capacity. [NIH] Exercise Tolerance: The exercise capacity of an individual as measured by endurance (maximal exercise duration and/or maximal attained work load) during an exercise test. [NIH]

Exocytosis: Cellular release of material within membrane-limited vesicles by fusion of the vesicles with the cell membrane. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Extracellular: Outside a cell or cells. [EU] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extracorporeal: Situated or occurring outside the body. [EU] Extraction: The process or act of pulling or drawing out. [EU] Extrarenal: Outside of the kidney. [EU] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]

Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] 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] Femoral: Pertaining to the femur, or to the thigh. [EU] Femoral Artery: The main artery of the thigh, a continuation of the external iliac artery. [NIH] Fentanyl: A narcotic opioid drug that is used in the treatment of pain. [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] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Filariasis: Infections with nematodes of the superfamily Filarioidea. The presence of living

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worms in the body is mainly asymptomatic but the death of adult worms leads to granulomatous inflammation and permanent fibrosis. Organisms of the genus Elaeophora infect wild elk and domestic sheep causing ischaemic necrosis of the brain, blindness, and dermatosis of the face. [NIH] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fluorescence Polarization: Measurement of the polarization of fluorescent light from solutions or microscopic specimens. It is used to provide information concerning molecular size, shape, and conformation, molecular anisotropy, electronic energy transfer, molecular interaction, including dye and coenzyme binding, and the antigen-antibody reaction. [NIH] Fluorescence Polarization Immunoassay: Fluoroimmunoassay where detection of the hapten-antibody reaction is based on measurement of the increased polarization of fluorescence-labeled hapten when it is combined with antibody. The assay is very useful for the measurement of small haptenic antigens such as drugs at low concentrations. [NIH] Fluorine: A nonmetallic, diatomic gas that is a trace element and member of the halogen family. It is used in dentistry as flouride to prevent dental caries. [NIH] Fluoxetine: The first highly specific serotonin uptake inhibitor. It is used as an antidepressant and often has a more acceptable side-effects profile than traditional antidepressants. [NIH] Flutter: A rapid vibration or pulsation. [EU] Foetoplacental: Pertaining to the fetus and placenta. [EU] Fold: A plication or doubling of various parts of the body. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Formulary: A book containing a list of pharmaceutical products with their formulas and means of preparation. [NIH] Free Radicals: Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. [NIH] Fructose: A type of sugar found in many fruits and vegetables and in honey. Fructose is used to sweeten some diet foods. It is considered a nutritive sweetener because it has calories. [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] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gastric: Having to do with the stomach. [NIH] Gastric Acid: Hydrochloric acid present in gastric juice. [NIH] Gastric Juices: Liquids produced in the stomach to help break down food and kill bacteria.

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[NIH]

Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

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] 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 Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Geriatric: Pertaining to the treatment of the aged. [EU] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Ginkgo biloba: Exclusive species of the genus Ginkgo, family Ginkgoacea. It produces extracts of medicinal interest. Ginkgo may refer to the genus or species. [NIH] 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] 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] Glucose Oxidase: An enzyme of the oxidoreductase class that catalyzes the conversion of beta-D-glucose and oxygen to D-glucono-1,5-lactone and peroxide. It is a flavoprotein,

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highly specific for beta-D-glucose. The enzyme is produced by Penicillium notatum and other fungi and has antibacterial activity in the presence of glucose and oxygen. It is used to estimate glucose concentration in blood or urine samples through the formation of colored dyes by the hydrogen peroxide produced in the reaction. (From Enzyme Nomenclature, 1992) EC 1.1.3.4. [NIH] Glucose tolerance: The power of the normal liver to absorb and store large quantities of glucose and the effectiveness of intestinal absorption of glucose. The glucose tolerance test is a metabolic test of carbohydrate tolerance that measures active insulin, a hepatic function based on the ability of the liver to absorb glucose. The test consists of ingesting 100 grams of glucose into a fasting stomach; blood sugar should return to normal in 2 to 21 hours after ingestion. [NIH] Glucose Tolerance Test: Determination of whole blood or plasma sugar in a fasting state before and at prescribed intervals (usually 1/2 hr, 1 hr, 3 hr, 4 hr) after taking a specified amount (usually 100 gm orally) of glucose. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [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] Glycosidic: Formed by elimination of water between the anomeric hydroxyl of one sugar and a hydroxyl of another sugar molecule. [NIH] Gonadal: Pertaining to a gonad. [EU] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Gram-negative: Losing the stain or decolorized by alcohol in Gram's method of staining, a primary characteristic of bacteria having a cell wall composed of a thin layer of peptidoglycan covered by an outer membrane of lipoprotein and lipopolysaccharide. [EU] Gram-positive: Retaining the stain or resisting decolorization by alcohol in Gram's method of staining, a primary characteristic of bacteria whose cell wall is composed of a thick layer of peptidologlycan with attached teichoic acids. [EU] Guanidine: A strong organic base existing primarily as guanidium ions at physiological pH. It is found in the urine as a normal product of protein metabolism. It is also used in laboratory research as a protein denaturant. (From Martindale, the Extra Pharmacopoeia, 30th ed and Merck Index, 12th ed) It is also used in the treatment of myasthenia and as a fluorescent probe in HPLC. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] 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] Haemoperfusion: 1. The act of pouring over or through, especially the passage of blood through the vessels of a specific organ. 2. Blood poured over or through an organ or tissue. [EU]

Hair follicles: Shafts or openings on the surface of the skin through which hair grows. [NIH] Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. [NIH]

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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] 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] Helminths: Commonly known as parasitic worms, this group includes the acanthocephala, nematoda, and platyhelminths. Some authors consider certain species of leeches that can become temporarily parasitic as helminths. [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] Hemolysis: The destruction of erythrocytes by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity. [NIH] Hepatic: Refers to the liver. [NIH] Hepatocellular: Pertaining to or affecting liver cells. [EU] 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]

Heterogenic: Derived from a different source or species. Also called heterogenous. [NIH] Heterogenous: Derived from a different source or species. Also called heterogenic. [NIH] Heterozygotes: Having unlike alleles at one or more corresponding loci on homologous chromosomes. [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]

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Histamine Release: The secretion of histamine from mast cell and basophil granules by exocytosis. This can be initiated by a number of factors, all of which involve binding of IgE, cross-linked by antigen, to the mast cell or basophil's Fc receptors. Once released, histamine binds to a number of different target cell receptors and exerts a wide variety of effects. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] 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] Homozygotes: An individual having a homozygous gene pair. [NIH] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Horseradish Peroxidase: An enzyme isolated from horseradish which is able to act as an antigen. It is frequently used as a histochemical tracer for light and electron microscopy. Its antigenicity has permitted its use as a combined antigen and marker in experimental immunology. [NIH] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridoma: A hybrid cell resulting from the fusion of a specific antibody-producing spleen cell with a myeloma cell. [NIH] Hydralazine: A direct-acting vasodilator that is used as an antihypertensive agent. [NIH] Hydrocodone: Narcotic analgesic related to codeine, but more potent and more addicting by weight. It is used also as cough suppressant. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] 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] Hyperbilirubinemia: Pathologic process consisting of an abnormal increase in the amount of bilirubin in the circulating blood, which may result in jaundice. [NIH]

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Hyperkalaemia: Pathology: an abnormally high concentration of potassium in the blood. [EU]

Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hyperthyroidism: Excessive functional activity of the thyroid gland. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hypnotic: A drug that acts to induce sleep. [EU] Hypothalamic: Of or involving the hypothalamus. [EU] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH] Hypoxic: Having too little oxygen. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Iloprost: An eicosanoid, derived from the cyclooxygenase pathway of arachidonic acid metabolism. It is a stable and synthetic analog of epoprostenol, but with a longer half-life than the parent compound. Its actions are similar to prostacyclin. Iloprost produces vasodilation and inhibits platelet aggregation. [NIH] Imaging procedures: Methods of producing pictures of areas inside the body. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]

effects

of

foreign

Immunoassay: Immunochemical assay or detection of a substance by serologic or immunologic methods. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance. [NIH] Immunogen: A substance that is capable of causing antibody formation. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Incubated: Grown in the laboratory under controlled conditions. (For instance, white blood cells can be grown in special conditions so that they attack specific cancer cells when

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returned to the body.) [NIH] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Indinavir: A potent and specific HIV protease inhibitor that appears to have good oral bioavailability. [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] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infections: The illnesses caused by an organism that usually does not cause disease in a person with a normal immune system. [NIH] Infestation: Parasitic attack or subsistence on the skin and/or its appendages, as by insects, mites, or ticks; sometimes used to denote parasitic invasion of the organs and tissues, as by helminths. [NIH] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Inflammatory bowel disease: A general term that refers to the inflammation of the colon and rectum. Inflammatory bowel disease includes ulcerative colitis and Crohn's disease. [NIH]

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] Inorganic: Pertaining to substances not of organic origin. [EU] Inotropic: Affecting the force or energy of muscular contractions. [EU] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Intensive Care: Advanced and highly specialized care provided to medical or surgical patients whose conditions are life-threatening and require comprehensive care and constant monitoring. It is usually administered in specially equipped units of a health care facility. [NIH]

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]

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Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intracellular Membranes: Membranes of subcellular structures. [NIH] Intracranial Aneurysm: A saclike dilatation of the walls of a blood vessel, usually an artery. [NIH]

Intracranial Arteriosclerosis: Vascular diseases characterized by thickening, hardening, and remodeling of the walls of intracranial arteries. There are three subtypes: (1) atherosclerosis, marked by fatty depositions in the innermost layer of the arterial walls, (2) Monckeberg's sclerosis, which features calcium deposition in the media and (3) arteriolosclerosis, which refers to sclerosis of small caliber arteries. Clinically, this process may be associated with transient ischemic attack, brain infarction, intracranial embolism and thrombosis, or intracranial aneurysm. [NIH] Intrahepatic: Within the liver. [NIH] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Involuntary: Reaction occurring without intention or volition. [NIH] Ion Transport: The movement of ions across energy-transducing cell membranes. Transport can be active or passive. Passive ion transport (facilitated diffusion) derives its energy from the concentration gradient of the ion itself and allows the transport of a single solute in one direction (uniport). Active ion transport is usually coupled to an energy-yielding chemical or photochemical reaction such as ATP hydrolysis. This form of primary active transport is called an ion pump. Secondary active transport utilizes the voltage and ion gradients produced by the primary transport to drive the cotransport of other ions or molecules. These may be transported in the same (symport) or opposite (antiport) direction. [NIH] Ionization: 1. Any process by which a neutral atom gains or loses electrons, thus acquiring a net charge, as the dissociation of a substance in solution into ions or ion production by the passage of radioactive particles. 2. Iontophoresis. [EU] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Isoenzyme: Different forms of an enzyme, usually occurring in different tissues. The isoenzymes of a particular enzyme catalyze the same reaction but they differ in some of their properties. [NIH] Isoprenoid: Molecule that might anchor G protein to the cell membrane as it is hydrophobic. [NIH]

Isosorbide Dinitrate: A vasodilator used in the treatment of angina. Its actions are similar to nitroglycerin but with a slower onset of action. [NIH] Itraconazole: An antifungal agent that has been used in the treatment of histoplasmosis, blastomycosis, cryptococcal meningitis, and aspergillosis. [NIH] Jaundice: A clinical manifestation of hyperbilirubinemia, consisting of deposition of bile pigments in the skin, resulting in a yellowish staining of the skin and mucous membranes. [NIH]

Jejunostomy: Surgical formation of an opening through the abdominal wall into the jejunum, usually for enteral hyperalimentation. [NIH] Jejunum: That portion of the small intestine which extends from the duodenum to the ileum; called also intestinum jejunum. [EU]

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Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Kidney Failure: The inability of a kidney to excrete metabolites at normal plasma levels under conditions of normal loading, or the inability to retain electrolytes under conditions of normal intake. In the acute form (kidney failure, acute), it is marked by uremia and usually by oliguria or anuria, with hyperkalemia and pulmonary edema. The chronic form (kidney failure, chronic) is irreversible and requires hemodialysis. [NIH] Kidney Failure, Acute: A clinical syndrome characterized by a sudden decrease in glomerular filtration rate, often to values of less than 1 to 2 ml per minute. It is usually associated with oliguria (urine volumes of less than 400 ml per day) and is always associated with biochemical consequences of the reduction in glomerular filtration rate such as a rise in blood urea nitrogen (BUN) and serum creatinine concentrations. [NIH] Kidney Failure, Chronic: An irreversible and usually progressive reduction in renal function in which both kidneys have been damaged by a variety of diseases to the extent that they are unable to adequately remove the metabolic products from the blood and regulate the body's electrolyte composition and acid-base balance. Chronic kidney failure requires hemodialysis or surgery, usually kidney transplantation. [NIH] Kinetic: Pertaining to or producing motion. [EU] Lactation: The period of the secretion of milk. [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] Lectin: A complex molecule that has both protein and sugars. Lectins are able to bind to the outside of a cell and cause biochemical changes in it. Lectins are made by both animals and plants. [NIH] Lenses: Pieces of glass or other transparent materials used for magnification or increased visual acuity. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] Leukemia: Cancer of blood-forming tissue. [NIH] Levofloxacin: A substance used to treat bacterial infections. It belongs to the family of drugs called quinolone antibiotics. [NIH] Levothyroxine: Levo isomer of the thyroid hormone thyroxine. It is used for replacement therapy in reduced or absent thyroid function. [NIH] Lidocaine: A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of procaine but its duration of action is shorter than that of bupivacaine or prilocaine. [NIH] Ligaments: Shiny, flexible bands of fibrous tissue connecting together articular extremities of bones. They are pliant, tough, and inextensile. [NIH] Ligands: A RNA simulation method developed by the MIT. [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lipid: Fat. [NIH] Liposomal: A drug preparation that contains the active drug in very tiny fat particles. This

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fat-encapsulated drug is absorbed better, and its distribution to the tumor site is improved. [NIH]

Liposome: A spherical particle in an aqueous medium, formed by a lipid bilayer enclosing an aqueous compartment. [EU] 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] Loa: A genus of parasitic nematodes found throughout the rain-forest areas of the Sudan and the basin of the Congo. L. loa inhabits the subcutaneous tissues, which it traverses freely. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH] Luciferase: Any one of several enzymes that catalyze the bioluminescent reaction in certain marine crustaceans, fish, bacteria, and insects. The enzyme is a flavoprotein; it oxidizes luciferins to an electronically excited compound that emits energy in the form of light. The color of light emitted varies with the organism. The firefly enzyme is a valuable reagent for measurement of ATP concentration. (Dorland, 27th ed) EC 1.13.12.-. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]

Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphedema: Edema due to obstruction of lymph vessels or disorders of the lymph nodes. [NIH]

Lymphocytes: White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each); those with characteristics of neither major class are called null cells. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Maintenance therapy: Treatment that is given to help a primary (original) treatment keep working. Maintenance therapy is often given to help keep cancer in remission. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH]

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Malignant tumor: A tumor capable of metastasizing. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]

Manic: Affected with mania. [EU] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] 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] 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] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. [NIH] Meningitis: Inflammation of the meninges. When it affects the dura mater, the disease is termed pachymeningitis; when the arachnoid and pia mater are involved, it is called leptomeningitis, or meningitis proper. [EU] Menopause: Permanent cessation of menstruation. [NIH] Menstrual Cycle: The period of the regularly recurring physiologic changes in the endometrium occurring during the reproductive period in human females and some primates and culminating in partial sloughing of the endometrium (menstruation). [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Health: The state wherein the person is well adjusted. [NIH] Mental Processes: Conceptual functions or thinking in all its forms. [NIH] Mesenteric: Pertaining to the mesentery : a membranous fold attaching various organs to the body wall. [EU] Mesentery: A layer of the peritoneum which attaches the abdominal viscera to the abdominal wall and conveys their blood vessels and nerves. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Methanol: A colorless, flammable liquid used in the manufacture of formaldehyde and acetic acid, in chemical synthesis, antifreeze, and as a solvent. Ingestion of methanol is toxic

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and may cause blindness. [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] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [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] Microspheres: Small uniformly-sized spherical particles frequently radioisotopes or various reagents acting as tags or markers. [NIH]

labeled

with

Midazolam: A short-acting compound, water-soluble at pH less than 4 and lipid-soluble at physiological pH. It is a hypnotic-sedative drug with anxiolytic and amnestic properties. It is used for sedation in dentistry, cardiac surgery, endoscopic procedures, as preanesthetic medication, and as an adjunct to local anesthesia. Because of its short duration and cardiorespiratory stability, it is particularly useful in poor-risk, elderly, and cardiac patients. [NIH]

Milk Thistle: The plant Silybum marianum in the family Asteraceae containing the bioflavonoid complex silymarin. For centuries this has been used traditionally to treat liver disease. [NIH] 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 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] Miosis: Pupillary constriction. This may result from congenital absence of the dilatator pupillary muscle, defective sympathetic innervation, or irritation of the conjunctiva or cornea. [NIH] Miotic: 1. Pertaining to, characterized by, or producing miosis : contraction of the pupil. 2. An agent that causes the pupil to contract. 3. Meiotic: characterized by cell division. [EU] Mitotic: Cell resulting from mitosis. [NIH] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Modulator: A specific inductor that brings out characteristics peculiar to a definite region. [EU]

Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecular Structure: The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. [NIH] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration,

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pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoamine: Enzyme that breaks down dopamine in the astrocytes and microglia. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monoclonal antibodies: Laboratory-produced substances that can locate and bind to cancer cells wherever they are in the body. Many monoclonal antibodies are used in cancer detection or therapy; each one recognizes a different protein on certain cancer cells. Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to a tumor. [NIH] Mucosa: A mucous membrane, or tunica mucosa. [EU] Multidrug resistance: Adaptation of tumor cells to anticancer drugs in ways that make the drugs less effective. [NIH] Multiple Myeloma: A malignant tumor of plasma cells usually arising in the bone marrow; characterized by diffuse involvement of the skeletal system, hyperglobulinemia, Bence-Jones proteinuria, and anemia. [NIH] Muscle Contraction: A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments. [NIH] Muscle relaxant: An agent that specifically aids in reducing muscle tension, as those acting at the polysynaptic neurons of motor nerves (e.g. meprobamate) or at the myoneural junction (curare and related compounds). [EU] Muscle Spindles: Mechanoreceptors found between skeletal muscle fibers. Muscle spindles are arranged in parallel with muscle fibers and respond to the passive stretch of the muscle, but cease to discharge if the muscle contracts isotonically, thus signaling muscle length. The muscle spindles are the receptors responsible for the stretch or myotactic reflex. [NIH] Myeloma: Cancer that arises in plasma cells, a type of white blood cell. [NIH] Myocardial Contraction: Contractile activity of the heart. [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] Myopia: That error of refraction in which rays of light entering the eye parallel to the optic axis are brought to a focus in front of the retina, as a result of the eyeball being too long from front to back (axial m.) or of an increased strength in refractive power of the media of the eye (index m.). Called also nearsightedness, because the near point is less distant than it is in emmetropia with an equal amplitude of accommodation. [EU] Myosin: Chief protein in muscle and the main constituent of the thick filaments of muscle fibers. In conjunction with actin, it is responsible for the contraction and relaxation of

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muscles. [NIH] Narcolepsy: A condition of unknown cause characterized by a periodic uncontrollable tendency to fall asleep. [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] Natriuresis: The excretion of abnormal amounts of sodium in the urine. [EU] 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] Nephrotoxic: Toxic or destructive to kidney cells. [EU] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Niacinamide: An important compound functioning as a component of the coenzyme NAD. Its primary significance is in the prevention and/or cure of blacktongue and pellagra. Most animals cannot manufacture this compound in amounts sufficient to prevent nutritional deficiency and it therefore must be supplemented through dietary intake. [NIH] Nicorandil: A derivative of the niacinamide that is structurally combined with an organic nitrate. It is a potassium-channel opener that causes vasodilatation of arterioles and large coronary arteries. Its nitrate-like properties produce venous vasodilation through stimulation of guanylate cyclase. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide

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activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]

Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Nitroglycerin: A highly volatile organic nitrate that acts as a dilator of arterial and venous smooth muscle and is used in the treatment of angina. It provides relief through improvement of the balance between myocardial oxygen supply and demand. Although total coronary blood flow is not increased, there is redistribution of blood flow in the heart when partial occlusion of coronary circulation is effected. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Normotensive: 1. Characterized by normal tone, tension, or pressure, as by normal blood pressure. 2. A person with normal blood pressure. [EU] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Occupational Medicine: Medical specialty concerned with the promotion and maintenance of the physical and mental health of employees in occupational settings. [NIH] Oestrogen: A generic term for oestrus-producing steroid compounds; the female sex hormones. In humans, oestrogen is formed in the ovary, possibly the adrenal cortex, the testis, and the foetoplacental unit; it has various functions in both sexes. It is responsible for the development of the female secondary sex characteristics, and during the menstrual cycle it acts on the female genitalia to produce an environment suitable for the fertilization, implantation, and nutrition of the early embryo. Oestrogen is used in oral contraceptives and as a palliative in cancer of the breast after menopause and cancer of the prostate; other uses include the relief of the discomforts of menopause, inhibition of lactation, and treatment of osteoporosis, threatened abortion, and various functional ovarian disorders. [EU]

Oliguria: Clinical manifestation of the urinary system consisting of a decrease in the amount of urine secreted. [NIH] Omeprazole: A highly effective inhibitor of gastric acid secretion used in the therapy of gastric ulcers and Zollinger-Ellison syndrome. The drug inhibits the H(+)-K(+)-ATPase (H(+)-K(+)-exchanging ATPase) in a pH-dependent manner. This ATPase is considered the proton pump in the secretory membrane of the parietal cell. [NIH] On-line: A sexually-reproducing population derived from a common parentage. [NIH] Oocytes: Female germ cells in stages between the prophase of the first maturation division and the completion of the second maturation division. [NIH] Opsin: A protein formed, together with retinene, by the chemical breakdown of meta-

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rhodopsin. [NIH] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] 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] Ouabain: A cardioactive glycoside consisting of rhamnose and ouabagenin, obtained from the seeds of Strophanthus gratus and other plants of the Apocynaceae; used like digitalis. It is commonly used in cell biological studies as an inhibitor of the NA(+)-K(+)-exchanging atpase. [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] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Overdose: An accidental or deliberate dose of a medication or street drug that is in excess of what is normally used. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). [NIH] Oxycodone: Semisynthetic derivative of codeine that acts as a narcotic analgesic more potent and addicting than codeine. [NIH] Oxygenator: An apparatus by which oxygen is introduced into the blood during circulation outside the body, as during open heart surgery. [NIH] Pacemaker: An object or substance that influences the rate at which a certain phenomenon occurs; often used alone to indicate the natural cardiac pacemaker or an artificial cardiac pacemaker. In biochemistry, a substance whose rate of reaction sets the pace for a series of interrelated reactions. [EU] 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] 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

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associated with hyperlipaemia, hyperparathyroidism, abdominal trauma (accidental or operative injury), vasculitis, or uraemia. [EU] Papain: A proteolytic enzyme obtained from Carica papaya. It is also the name used for a purified mixture of papain and chymopapain that is used as a topical enzymatic debriding agent. EC 3.4.22.2. [NIH] Parasite: An animal or a plant that lives on or in an organism of another species and gets at least some of its nutrition from that other organism. [NIH] Parasitic: Having to do with or being a parasite. A parasite is an animal or a plant that lives on or in an organism of another species and gets at least some of its nutrients from it. [NIH] Parietal: 1. Of or pertaining to the walls of a cavity. 2. Pertaining to or located near the parietal bone, as the parietal lobe. [EU] Parotid: The space that contains the parotid gland, the facial nerve, the external carotid artery, and the retromandibular vein. [NIH] Paroxetine: A serotonin uptake inhibitor that is effective in the treatment of depression. [NIH]

Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Particle: A tiny mass of material. [EU] Pathogen: Any disease-producing microorganism. [EU] Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pepsin: An enzyme made in the stomach that breaks down proteins. [NIH] Peptic: Pertaining to pepsin or to digestion; related to the action of gastric juices. [EU] Peptic Ulcer: An ulceration of the mucous membrane of the esophagus, stomach or duodenum, caused by the action of the acid gastric juice. [NIH] 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] Perception: The ability quickly and accurately to recognize similarities and differences among presented objects, whether these be pairs of words, pairs of number series, or multiple sets of these or other symbols such as geometric figures. [NIH] 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] Perinatal: Pertaining to or occurring in the period shortly before and after birth; variously defined as beginning with completion of the twentieth to twenty-eighth week of gestation and ending 7 to 28 days after birth. [EU] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH]

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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] Peroxide: Chemical compound which contains an atom group with two oxygen atoms tied to each other. [NIH] P-Glycoprotein: A 170 kD transmembrane glycoprotein from the superfamily of ABC transporters. It serves as an ATP-dependent efflux pump for a variety of chemicals, including many antineoplastic agents. Overexpression of this glycoprotein is associated with multidrug resistance. [NIH] Pharmaceutical Preparations: Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form. [NIH] Pharmacodynamic: Is concerned with the response of living tissues to chemical stimuli, that is, the action of drugs on the living organism in the absence of disease. [NIH] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharmacotherapy: A regimen of using appetite suppressant medications to manage obesity by decreasing appetite or increasing the feeling of satiety. These medications decrease appetite by increasing serotonin or catecholamine—two brain chemicals that affect mood and appetite. [NIH] Phenyl: Ingredient used in cold and flu remedies. [NIH] Phenytoin: An anticonvulsant that is used in a wide variety of seizures. It is also an antiarrhythmic and a muscle relaxant. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, active transport, and general membrane stabilization. The mechanism of its muscle relaxant effect appears to involve a reduction in the sensitivity of muscle spindles to stretch. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Physical Therapy: The restoration of function and the prevention of disability following disease or injury with the use of light, heat, cold, water, electricity, ultrasound, and exercise. [NIH]

Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized

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by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma 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] Plasmapheresis: Procedure whereby plasma is separated and extracted from anticoagulated whole blood and the red cells retransfused to the donor. Plasmapheresis is also employed for therapeutic use. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelet Count: A count of the number of platelets per unit volume in a sample of venous blood. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Pneumonia: Inflammation of the lungs. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Pollen: The male fertilizing element of flowering plants analogous to sperm in animals. It is 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]

Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [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] 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

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health care and delivery. [NIH] Precipitation: The act or process of precipitating. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] 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] Preeclampsia: A toxaemia of late pregnancy characterized by hypertension, edema, and proteinuria, when convulsions and coma are associated, it is called eclampsia. [EU] Pre-eclamptic: A syndrome characterized by hypertension, albuminuria, and generalized oedema, occurring only in pregnancy. [NIH] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] 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] Probenecid: The prototypical uricosuric agent. It inhibits the renal excretion of organic anions and reduces tubular reabsorption of urate. Probenecid has also been used to treat patients with renal impairment, and, because it reduces the renal tubular excretion of other drugs, has been used as an adjunct to antibacterial therapy. [NIH] Procaine: A local anesthetic of the ester type that has a slow onset and a short duration of action. It is mainly used for infiltration anesthesia, peripheral nerve block, and spinal block. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1016). [NIH] 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] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Propafenone: An antiarrhythmia agent that is particularly effective in ventricular arrhythmias. It also has weak beta-blocking activity. The drug is generally well tolerated. [NIH]

Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Propranolol: A widely used non-cardioselective beta-adrenergic antagonist. Propranolol is used in the treatment or prevention of many disorders including acute myocardial infarction, arrhythmias, angina pectoris, hypertension, hypertensive emergencies, hyperthyroidism, migraine, pheochromocytoma, menopause, and anxiety. [NIH]

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Propylene Glycol: A clear, colorless, viscous organic solvent and diluent used in pharmaceutical preparations. [NIH] Proscillaridin: A cardiotonic glycoside isolated from Scilla maritima var. alba (Squill). [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond (5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane). The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also). The effect produced by the cyclic AMP increase depends on the specific cell type. In some cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protease Inhibitors: Compounds which inhibit or antagonize biosynthesis or actions of proteases (endopeptidases). [NIH] Protective Agents: Synthetic or natural substances which are given to prevent a disease or disorder or are used in the process of treating a disease or injury due to a poisonous agent. [NIH]

Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific proteinbinding measures are often used as assays in diagnostic assessments. [NIH] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not

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working properly. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Proton Pump: Integral membrane proteins that transport protons across a membrane against a concentration gradient. This transport is driven by hydrolysis of ATP by H(+)transporting ATP synthase. [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] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychoactive: Those drugs which alter sensation, mood, consciousness or other psychological or behavioral functions. [NIH] Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Psychotomimetic: Psychosis miming. [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 Circulation: The circulation of blood through the lungs. [NIH] Pulmonary Edema: An accumulation of an excessive amount of watery fluid in the lungs, may be caused by acute exposure to dangerous concentrations of irritant gasses. [NIH] Pulmonary Embolism: Embolism in the pulmonary artery or one of its branches. [NIH] Pulmonary hypertension: Abnormally high blood pressure in the arteries of the lungs. [NIH] 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]

Pupil: The aperture in the iris through which light passes. [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

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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 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] 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] Racemic: Optically inactive but resolvable in the way of all racemic compounds. [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] Radioactivity: The quality of emitting or the emission of corpuscular or electromagnetic radiations consequent to nuclear disintegration, a natural property of all chemical elements of atomic number above 83, and possible of induction in all other known elements. [EU] Radioimmunoassay: Classic quantitative assay for detection of antigen-antibody reactions using a radioactively labeled substance (radioligand) either directly or indirectly to measure the binding of the unlabeled substance to a specific antibody or other receptor system. Nonimmunogenic substances (e.g., haptens) can be measured if coupled to larger carrier proteins (e.g., bovine gamma-globulin or human serum albumin) capable of inducing antibody formation. [NIH] Radioisotope: An unstable element that releases radiation as it breaks down. Radioisotopes can be used in imaging tests or as a treatment for cancer. [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] 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] Reaction Time: The time from the onset of a stimulus until the organism responds. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH]

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Receptors, Adrenergic: Cell-surface proteins that bind epinephrine and/or norepinephrine with high affinity and trigger intracellular changes. The two major classes of adrenergic receptors, alpha and beta, were originally discriminated based on their cellular actions but now are distinguished by their relative affinity for characteristic synthetic ligands. Adrenergic receptors may also be classified according to the subtypes of G-proteins with which they bind; this scheme does not respect the alpha-beta distinction. [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] 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] Reflex: An involuntary movement or exercise of function in a part, excited in response to a stimulus applied to the periphery and transmitted to the brain or spinal cord. [NIH] 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] 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] Reliability: Used technically, in a statistical sense, of consistency of a test with itself, i. e. the extent to which we can assume that it will yield the same result if repeated a second time. [NIH]

Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renal Artery: A branch of the abdominal aorta which supplies the kidneys, adrenal glands and ureters. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Renal tubular: A defect in the kidneys that hinders their normal excretion of acids. Failure to excrete acids can lead to weak bones, kidney stones, and poor growth in children. [NIH] Renin: An enzyme which is secreted by the kidney and is formed from prorenin in plasma and kidney. The enzyme cleaves the Leu-Leu bond in angiotensinogen to generate angiotensin I. EC 3.4.23.15. (Formerly EC 3.4.99.19). [NIH] Renin-Angiotensin System: A system consisting of renin, angiotensin-converting enzyme, and angiotensin II. Renin, an enzyme produced in the kidney, acts on angiotensinogen, an alpha-2 globulin produced by the liver, forming angiotensin I. The converting enzyme contained in the lung acts on angiotensin I in the plasma converting it to angiotensin II, the most powerful directly pressor substance known. It causes contraction of the arteriolar smooth muscle and has other indirect actions mediated through the adrenal cortex. [NIH]

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Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Resuscitation: The restoration to life or consciousness of one apparently dead; it includes such measures as artificial respiration and cardiac massage. [EU] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retinal Detachment: Separation of the inner layers of the retina (neural retina) from the pigment epithelium. Retinal detachment occurs more commonly in men than in women, in eyes with degenerative myopia, in aging and in aphakia. It may occur after an uncomplicated cataract extraction, but it is seen more often if vitreous humor has been lost during surgery. (Dorland, 27th ed; Newell, Ophthalmology: Principles and Concepts, 7th ed, p310-12). [NIH] Retinol: Vitamin A. It is essential for proper vision and healthy skin and mucous membranes. Retinol is being studied for cancer prevention; it belongs to the family of drugs called retinoids. [NIH] 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] Rhamnose: A methylpentose whose L- isomer is found naturally in many plant glycosides and some gram-negative bacterial lipopolysaccharides. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rhinitis: Inflammation of the mucous membrane of the nose. [NIH] Rhodopsin: A photoreceptor protein found in retinal rods. It is a complex formed by the binding of retinal, the oxidized form of retinol, to the protein opsin and undergoes a series of complex reactions in response to visible light resulting in the transmission of nerve impulses to the brain. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Ritonavir: An HIV protease inhibitor that works by interfering with the reproductive cycle of HIV. [NIH] Rods: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide side vision and the ability to see objects in dim light (night vision). [NIH]

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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] Saponins: Sapogenin glycosides. A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycon moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics when injected into the blood stream able to dissolve red blood cells at even extreme dilutions. [NIH] Sarcoidosis: An idiopathic systemic inflammatory granulomatous disorder comprised of epithelioid and multinucleated giant cells with little necrosis. It usually invades the lungs with fibrosis and may also involve lymph nodes, skin, liver, spleen, eyes, phalangeal bones, and parotid glands. [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] Sebaceous: Gland that secretes sebum. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Sedative: 1. Allaying activity and excitement. 2. An agent that allays excitement. [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] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] 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]

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Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]

Shunt: A surgically created diversion of fluid (e.g., blood or cerebrospinal fluid) from one area of the body to another area of the body. [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] Silicon: A trace element that constitutes about 27.6% of the earth's crust in the form of silicon dioxide. It does not occur free in nature. Silicon has the atomic symbol Si, atomic number 14, and atomic weight 28.09. [NIH] Silicon Dioxide: Silica. Transparent, tasteless crystals found in nature as agate, amethyst, chalcedony, cristobalite, flint, sand, quartz, and tridymite. The compound is insoluble in water or acids except hydrofluoric acid. [NIH] Silymarin: A mixture of flavonoids extracted from seeds of the milk thistle, Silybum marianum. It consists primarily of three isomers: silicristin, silidianin, and silybin, its major component. Silymarin displays antioxidant and membrane stabilizing activity. It protects various tissues and organs against chemical injury, and shows potential as an antihepatoxic agent. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

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] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic

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system. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Sotalol: An adrenergic beta-antagonist that is used in the treatment of life-threatening arrhythmias. [NIH] Sound wave: An alteration of properties of an elastic medium, such as pressure, particle displacement, or density, that propagates through the medium, or a superposition of such alterations. [NIH] 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] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Stabilization: The creation of a stable state. [EU] Steady state: Dynamic equilibrium. [EU] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]

Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Striate: Recurrent branch of the anterior cerebral artery which supplies the anterior limb of the internal capsule. [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] Strontium: An element of the alkaline earth family of metals. It has the atomic symbol Sr, atomic number 38, and atomic weight 87.62. [NIH]

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Strophanthins: A number of different cardioactive glycosides obtained from Strophanthus species. ouabain is from S. gratus and cymarine from S. kombe. They are used like the digitalis glycosides. [NIH] 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] Subliminal: Below the threshold of sensation, as a subliminal stimulus. [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] Sulfur: An element that is a member of the chalcogen family. It has an atomic symbol S, atomic number 16, and atomic weight 32.066. It is found in the amino acids cysteine and methionine. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Supraventricular: Situated or occurring above the ventricles, especially in an atrium or atrioventricular node. [EU] Sympathetic Nervous System: The thoracolumbar division of the autonomic nervous system. Sympathetic preganglionic fibers originate in neurons of the intermediolateral column of the spinal cord and project to the paravertebral and prevertebral ganglia, which in turn project to target organs. The sympathetic nervous system mediates the body's response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system. [NIH] Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Systemic: Affecting the entire body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tachycardia: Excessive rapidity in the action of the heart, usually with a heart rate above 100 beats per minute. [NIH] Tardive: Marked by lateness, late; said of a disease in which the characteristic lesion is late in appearing. [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] Teratogenic: Tending to produce anomalies of formation, or teratism (= anomaly of formation or development : condition of a monster). [EU]

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Testicular: Pertaining to a testis. [EU] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [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] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]

Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Ticks: Blood-sucking arachnids of the order Acarina. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tone: 1. The normal degree of vigour and tension; in muscle, the resistance to passive elongation or stretch; tonus. 2. A particular quality of sound or of voice. 3. To make permanent, or to change, the colour of silver stain by chemical treatment, usually with a heavy metal. [EU] Tonic: 1. Producing and restoring the normal tone. 2. Characterized by continuous tension. 3. A term formerly used for a class of medicinal preparations believed to have the power of restoring normal tone to tissue. [EU] Tonicity: The normal state of muscular tension. [NIH] Tonus: A state of slight tension usually present in muscles even when they are not undergoing active contraction. [NIH] Topical: On the surface of the body. [NIH]

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Torsion: A twisting or rotation of a bodily part or member on its axis. [NIH] Toxaemia: 1. The condition resulting from the spread of bacterial products (toxins) by the bloodstream. 2. A condition resulting from metabolic disturbances, e.g. toxaemia of pregnancy. [EU] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU] Toxoplasmosis: The acquired form of infection by Toxoplasma gondii in animals and man. [NIH]

Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Tracer: A substance (such as a radioisotope) used in imaging procedures. [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translocating: The attachment of a fragment of one chromosome to a non-homologous chromosome. [NIH] Translocation: The movement of material in solution inside the body of the plant. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Trichloroacetic Acid: A strong acid used as a protein precipitant in clinical chemistry and also as a caustic for removing warts. [NIH] Tricuspid Atresia: Absence of the orifice between the right atrium and ventricle, with the presence of an atrial defect through which all the systemic venous return reaches the left heart. As a result, there is left ventricular hypertrophy because the right ventricle is absent or not functional. [NIH] Tricyclic: Containing three fused rings or closed chains in the molecular structure. [EU] Tunica: A rather vague term to denote the lining coat of hollow organs, tubes, or cavities. [NIH]

Type 2 diabetes: Usually characterized by a gradual onset with minimal or no symptoms of metabolic disturbance and no requirement for exogenous insulin. The peak age of onset is 50 to 60 years. Obesity and possibly a genetic factor are usually present. [NIH] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH]

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Ulceration: 1. The formation or development of an ulcer. 2. An ulcer. [EU] Uraemia: 1. An excess in the blood of urea, creatinine, and other nitrogenous end products of protein and amino acids metabolism; more correctly referred to as azotemia. 2. In current usage the entire constellation of signs and symptoms of chronic renal failure, including nausea, vomiting anorexia, a metallic taste in the mouth, a uraemic odour of the breath, pruritus, uraemic frost on the skin, neuromuscular disorders, pain and twitching in the muscles, hypertension, edema, mental confusion, and acid-base and electrolyte imbalances. [EU]

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] Ureters: Tubes that carry urine from the kidneys to the bladder. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Uricosuric: 1. Pertaining to, characterized by, or promoting uricosuria (= the excretion of uric acid in the urine). 2. An agent that promotes uricosuria. [EU] 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] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] 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] Varicose: The common ulcer in the lower third of the leg or near the ankle. [NIH] Varicose vein: An abnormal swelling and tortuosity especially of the superficial veins of the legs. [EU] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vascular Resistance: An expression of the resistance offered by the systemic arterioles, and to a lesser extent by the capillaries, to the flow of blood. [NIH] Vasculitis: Inflammation of a blood vessel. [NIH] Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [NIH] Vasodilatation: A state of increased calibre of the blood vessels. [EU] Vasodilation: Physiological dilation of the blood vessels without anatomic change. For dilation with anatomic change, dilatation, pathologic or aneurysm (or specific aneurysm) is used. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] VE: The total volume of gas either inspired or expired in one minute. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venom: That produced by the poison glands of the mouth and injected by the fangs of poisonous snakes. [NIH]

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Venous: Of or pertaining to the veins. [EU] Venous blood: Blood that has given up its oxygen to the tissues and carries carbon dioxide back for gas exchange. [NIH] Venous Thrombosis: The formation or presence of a thrombus within a vein. [NIH] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] 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] Veterinarians: Individuals with a degree in veterinary medicine that provides them with training and qualifications to treat diseases and injuries of animals. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Vinblastine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. It is a mitotic inhibitor. [NIH] Vinca Alkaloids: A class of alkaloids from the genus of apocyanaceous woody herbs including periwinkles. They are some of the most useful antineoplastic agents. [NIH] Vincristine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Visual Acuity: Acuteness or clearness of vision, especially of form vision, which is dependent mainly on the sharpness of the retinal focus. [NIH] Vitreous: Glasslike or hyaline; often used alone to designate the vitreous body of the eye (corpus vitreum). [EU] Vitreous Humor: The transparent, colorless mass of gel that lies behind the lens and in front of the retina and fills the center of the eyeball. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Vulgaris: An affection of the skin, especially of the face, the back and the chest, due to chronic inflammation of the sebaceous glands and the hair follicles. [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]

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Warts: Benign epidermal proliferations or tumors; some are viral in origin. [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] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]

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INDEX A Abdominal, 145, 170, 176, 179, 184, 185, 186, 192 Absolute risk, 6, 11, 145 Acceptor, 145, 184 ACE, 70, 104, 113, 114, 145 Acetaminophen, 39, 145 Acetylcholine, 101, 145, 157, 182 Actin, 145, 181 Acute renal, 10, 112, 145 Adenine, 145 Adenosine, 58, 145, 147, 154, 186, 198 Adrenal Cortex, 12, 145, 146, 161, 183, 188, 192 Adrenal Glands, 145, 147, 192 Adrenergic, 145, 146, 149, 165, 167, 180, 188, 191, 192, 196, 197 Adsorption, 52, 54, 145 Adsorptive, 145 Adverse Effect, 48, 118, 145, 186, 195 Aerosol, 3, 145 Affinity, 8, 48, 96, 105, 146, 192, 195 Age of Onset, 146, 199 Agonist, 146, 165, 167 Albumin, 22, 92, 98, 107, 146, 180, 187 Aldosterone, 114, 115, 146, 154 Alertness, 146, 154 Algorithms, 146, 153 Alkaline, 146, 154, 196 Alkaloid, 146, 152, 190, 191, 198 Alprenolol, 146, 180 Alternative medicine, 121, 146 Aluminum, 107, 146 Ambulatory Care, 146 Amine, 146, 172 Amino Acid Sequence, 147, 149 Amino Acids, 147, 148, 167, 185, 189, 197, 199, 200 Amiodarone, 22, 24, 26, 49, 52, 147 Amlodipine, 3, 103, 104, 147 Amnestic, 147, 180 Amnion, 147 Amniotic Fluid, 107, 147 Amoxicillin, 3, 147 Amphetamine, 147, 163 Ampicillin, 147 Amplification, 100, 109, 110, 147 Amyloid, 6, 147, 157

Amyloidosis, 6, 83, 147 Anaerobic, 35, 148 Anaesthesia, 38, 148, 175 Analgesic, 10, 145, 148, 159, 163, 173, 184, 191 Analog, 108, 148, 174 Analytes, 48, 100, 102, 105, 148 Anatomical, 148, 151, 157, 160, 164, 174 Androgens, 145, 148 Anemia, 148, 181 Anesthesia, 148, 180, 188 Aneurysm, 148, 200 Angina, 147, 148, 149, 176, 180, 183, 188 Angina Pectoris, 147, 148, 180, 188 Anginal, 146, 148, 149 Angiopathy, 148, 157 Angiotensin converting enzyme inhibitor, 113, 114, 115, 148 Angiotensin-Converting Enzyme Inhibitors, 34, 58, 148 Angiotensinogen, 148, 192 Animal model, 9, 148 Anions, 146, 149, 176, 188, 194 Anisotropy, 149, 169 Ankle, 149, 200 Antagonism, 149, 154, 164, 198 Anthelmintic, 149, 163 Antianginal, 44, 65, 147, 149 Anti-Arrhythmia Agents, 149, 164 Antiarrhythmic, 26, 29, 44, 65, 147, 149 Antibacterial, 149, 171, 188 Antibiotic, 147, 149, 151, 154, 156, 157, 158, 162, 165, 167 Antibodies, 18, 19, 40, 58, 92, 93, 96, 97, 105, 149, 172, 181, 187 Antibody Specificity, 23, 149 Anticholinergic, 149, 164 Anticoagulant, 149, 189, 201 Anticonvulsant, 118, 149, 155, 186 Antidepressant, 9, 149, 158, 169 Antidote, 58, 119, 149 Antiepileptic, 52, 56, 149 Antifungal, 150, 176 Antigen, 45, 95, 100, 105, 108, 146, 149, 150, 159, 169, 173, 174, 179, 191 Antihypertensive, 39, 146, 150, 173 Anti-inflammatory, 145, 150, 170, 188 Antimicrobial, 21, 150, 156

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Antineoplastic, 150, 165, 186, 201 Antineoplastic Agents, 150, 186, 201 Antioxidant, 150, 151, 195 Antipyretic, 145, 150, 191 Antivirals, 9, 150 Anuria, 150, 177 Anus, 150, 154, 159 Anxiety, 150, 188 Anxiolytic, 150, 180 Aorta, 150, 155, 192, 201 Aphakia, 150, 193 Aqueous, 98, 106, 109, 150, 152, 162, 173, 178 Arachidonic Acid, 150, 174, 189 Arginine, 30, 150, 182 Arrhythmogenic, 29, 150 Arterial, 150, 155, 157, 161, 174, 176, 183, 189, 197 Arteries, 148, 150, 153, 161, 176, 181, 182, 190 Arteriolar, 150, 154, 192 Arterioles, 12, 150, 153, 154, 181, 182, 200 Arteriovenous, 150, 157 Artery, 37, 93, 94, 148, 150, 157, 161, 166, 168, 176, 185, 190, 196 Ascorbic Acid, 74, 151 Aspergillosis, 151, 176 Asymptomatic, 151, 169, 184 Atrial, 22, 24, 25, 26, 27, 31, 32, 34, 39, 43, 45, 52, 59, 73, 99, 103, 120, 147, 151, 161, 199, 201 Atrial Fibrillation, 22, 24, 25, 26, 27, 32, 39, 43, 45, 52, 59, 73, 99, 103, 120, 151, 201 Atrial Flutter, 103, 151 Atrial Function, 31, 151 Atrioventricular, 69, 151, 161, 197 Atrioventricular Node, 151, 197 Atrium, 151, 155, 161, 197, 199, 201 Attenuated, 151, 164 Autodigestion, 151, 184 Autonomic Nervous System, 151, 185, 197 Autopsy, 22, 69, 151 Axons, 13, 151 Azithromycin, 3, 84, 151 B Bacteria, 145, 149, 150, 151, 152, 158, 160, 163, 166, 168, 169, 171, 172, 178, 180, 199 Bacterial Infections, 151, 177 Bacteriostatic, 151, 167 Basal Ganglia, 151, 152, 157 Basal Ganglia Diseases, 152, 157 Base, 10, 145, 152, 171, 177, 197, 200

Basophil, 152, 173 Berberine, 94, 152 Beta blocker, 58, 152 Beta-pleated, 147, 152 Bile, 8, 65, 66, 152, 169, 176, 178, 196 Bile Acids, 152, 196 Bile Acids and Salts, 152 Bile duct, 66, 152 Biliary, 47, 50, 51, 152, 184 Biliary Tract, 152, 184 Bilirubin, 146, 152, 173 Binding Sites, 98, 108, 152 Bioavailability, 14, 17, 22, 24, 27, 49, 53, 65, 78, 103, 118, 152, 175 Biochemical, 8, 30, 73, 82, 100, 152, 177, 194 Bioluminescence, 94, 152 Bioreactors, 69, 152 Biosynthesis, 150, 152, 189 Biotechnology, 17, 20, 69, 117, 121, 129, 153 Biotransformation, 12, 153 Bladder, 153, 157, 159, 174, 189, 200 Blastocyst, 153, 160, 186 Blastomycosis, 153, 176 Blood Coagulation, 153, 154, 198 Blood Glucose, 153, 172 Blood pressure, 12, 64, 112, 143, 150, 153, 155, 156, 174, 181, 183, 190, 195 Blood-Brain Barrier, 14, 153 Blot, 17, 153 Body Fluids, 98, 153, 154, 165, 195 Bolus, 112, 153 Bolus infusion, 153 Bone Marrow, 153, 162, 178, 181, 195 Bowel, 153, 154, 175, 186, 196 Bowel Movement, 154, 196 Bradycardia, 27, 154 Bradykinin, 154, 182, 187 Broad-spectrum, 147, 154 Bromine, 113, 154 Bronchi, 154, 198 Bronchial, 35, 101, 154, 172, 198 Bronchitis, 36, 154 Bupivacaine, 154, 177 Bypass, 22, 154 C Cachexia, 56, 154 Caffeine, 74, 154 Calcium, 6, 24, 32, 35, 47, 50, 51, 55, 58, 59, 64, 67, 73, 107, 147, 149, 154, 159, 164, 176, 201

205

Calcium Channel Blockers, 6, 58, 154 Canrenone, 21, 24, 39, 154 Capillary, 25, 48, 154, 194, 201 Capsules, 155, 167 Captopril, 55, 66, 155 Carbamazepine, 9, 118, 155 Carbohydrate, 92, 155, 171, 187 Carbon Dioxide, 76, 155, 162, 186, 193, 201 Carboxy, 97, 155 Carcinogenic, 155, 188, 196 Carcinoma, 72, 155 Cardenolides, 12, 18, 70, 155 Cardiac, 6, 12, 13, 16, 19, 27, 28, 29, 31, 46, 55, 56, 60, 82, 84, 92, 94, 95, 97, 98, 99, 100, 101, 103, 104, 106, 109, 110, 111, 114, 115, 149, 151, 154, 155, 156, 161, 164, 166, 168, 177, 180, 181, 184, 190, 193, 196 Cardiac arrest, 29, 155 Cardiac Glycosides, 16, 27, 84, 94, 95, 106, 107, 111, 114, 155, 164 Cardiac Output, 155, 156 Cardiogenic, 95, 155 Cardiomyopathy, 6, 115, 134, 155 Cardiopulmonary, 34, 155 Cardiopulmonary Bypass, 34, 155 Cardiorespiratory, 155, 180 Cardioselective, 155, 188 Cardiotonic, 13, 99, 106, 111, 155, 156, 163, 164, 189 Cardiotonic Agents, 106, 156 Cardiovascular, 6, 12, 32, 46, 59, 66, 95, 110, 114, 115, 147, 156, 168, 194 Cardiovascular disease, 6, 12, 114, 115, 156 Cardioversion, 59, 156 Carmine, 114, 156 Carotene, 156, 193 Carrier Proteins, 156, 187, 191 Case report, 25, 53, 57, 156 Cataract, 150, 156, 193 Catecholamine, 156, 165, 186 Cations, 156, 176 Causal, 156, 172 Caustic, 156, 199 Cell Division, 151, 156, 180, 187, 188 Cell membrane, 154, 156, 163, 168, 176 Central Nervous System, 145, 147, 151, 154, 156, 157, 163, 167, 169, 172, 194, 198 Cephalexin, 4, 156 Cephaloridine, 156 Cephalothin, 156, 157

Cerebral, 28, 35, 36, 65, 76, 77, 112, 152, 153, 157, 160, 161, 167, 196 Cerebral Cortex, 157, 167 Cerebral Hemorrhage, 28, 112, 157 Cerebral Infarction, 157 Cerebrospinal, 157, 195 Cerebrospinal fluid, 157, 195 Cerebrovascular, 152, 154, 156, 157 Cerebrum, 157 Chin, 157, 179 Chlorine, 113, 157 Cholesterol, 51, 152, 157, 161, 196 Cholinesterase Inhibitors, 157, 165 Chorea, 34, 157 Choreatic Disorders, 157 Chromatin, 158, 178 Chromosomal, 147, 158 Chromosome, 158, 160, 172, 177, 199 Chronic Disease, 154, 158 Chronic renal, 158, 169, 200 Chymopapain, 158, 185 Circulatory system, 101, 158 Cirrhosis, 35, 158 CIS, 111, 158, 193 Citalopram, 40, 158 Clarithromycin, 9, 21, 25, 26, 27, 30, 55, 84, 158 Clear cell carcinoma, 158, 163 Clinical Medicine, 48, 57, 158, 188 Clinical trial, 4, 9, 64, 129, 158, 160, 162, 165, 191 Cloning, 14, 153, 158 Coagulation, 153, 158, 187, 201 Codeine, 159, 173, 184 Coenzyme, 151, 159, 169, 182 Cofactor, 159, 189, 198 Colitis, 159, 175 Colloidal, 146, 159, 166, 194 Colon, 72, 159, 175, 177 Combination Therapy, 56, 159 Complement, 159, 170, 187 Complementary and alternative medicine, 69, 87, 159 Complementary medicine, 69, 159 Compliance, 15, 51, 64, 118, 159 Computational Biology, 129, 160 Conception, 160, 168 Concomitant, 6, 26, 32, 160 Conduction, 99, 149, 151, 160 Cones, 160, 193 Conjugated, 3, 104, 152, 160, 162 Conjugation, 153, 160

206

Digoxin

Connective Tissue, 151, 153, 160, 168, 169, 178 Consciousness, 148, 160, 165, 190, 193 Constriction, 16, 94, 101, 160, 180, 200 Constriction, Pathologic, 160, 200 Contractility, 94, 148, 160 Contraindications, ii, 160 Control group, 4, 5, 6, 7, 160 Convulsions, 149, 160, 165, 188 Coordination, 11, 71, 77, 160 Cor, 95, 160 Coronary, 94, 105, 148, 151, 156, 161, 181, 182, 183 Coronary Arteriosclerosis, 161, 181 Coronary heart disease, 156, 161 Coronary Thrombosis, 161, 181 Corpus, 161, 188, 201 Corpus Luteum, 161, 188 Cortex, 12, 161 Cortical, 112, 161, 194 Cortical Blindness, 112, 161 Cortisol, 146, 161 Cortisone, 161, 188 Creatine, 100, 161 Creatine Kinase, 100, 161 Creatinine, 51, 53, 161, 162, 177, 200 Creatinine clearance, 51, 162 Cryptosporidiosis, 151, 162 Curative, 162, 198 Cyclic, 17, 38, 154, 162, 171, 183, 189, 198 Cyclosporine, 9, 13, 84, 162 Cysteine, 14, 158, 162, 197 Cystine, 162 Cytochrome, 9, 13, 38, 44, 162 Cytoplasm, 156, 162, 178 D Data Collection, 11, 162 Daunorubicin, 162, 165 Decarboxylation, 162, 172 Decidua, 162, 186 Degenerative, 162, 193 Demethylation, 9, 162 Dental Caries, 162, 169 Depolarization, 163, 164 Depressive Disorder, 163, 178 DES, 117, 163 Detoxification, 8, 9, 163 Deuterium, 163, 173 Dexmedetomidine, 27, 163 Dextroamphetamine, 101, 147, 163 Diabetes Mellitus, 163, 170, 172, 175 Diagnostic Errors, 163, 179

Diagnostic procedure, 91, 121, 163 Dialyzer, 163, 172 Diastole, 163 Diastolic, 57, 59, 163, 174 Diastolic heart failure, 57, 163 Diethylcarbamazine, 101, 163 Diffusion, 163, 164, 171, 176 Digestion, 152, 153, 163, 175, 178, 185, 196 Digitalis Glycosides, 97, 105, 113, 114, 164, 197 Digitoxigenin, 64, 164 Digoxigenin, 44, 92, 97, 164 Dihydrotestosterone, 164, 192 Dihydroxy, 103, 111, 146, 164, 194 Dilatation, Pathologic, 164, 200 Dilated cardiomyopathy, 43, 164 Dilation, 154, 164, 200 Dilator, 101, 164, 183 Diltiazem, 20, 22, 48, 164 Dilution, 18, 27, 164 Dimethyl, 106, 107, 108, 164 Diploid, 164, 187 Direct, iii, 24, 48, 111, 123, 156, 158, 164, 165, 173, 191, 192 Dirofilaria, 102, 164 Dirofilaria immitis, 102, 164 Discrete, 101, 164 Disopyramide, 34, 164 Disposition, 8, 9, 13, 14, 50, 65, 74, 118, 164 Dissociation, 102, 146, 164, 176 Dissociative Disorders, 164, 165 Distal, 165, 166 Diuresis, 28, 154, 165, 198 Diuretic, 56, 103, 104, 113, 114, 165, 169 Dominance, 32, 35, 36, 37, 65, 71, 76, 77, 165 Donepezil, 27, 165 Dopamine, 147, 163, 165, 181, 182 Double-blind, 15, 43, 165 Doxorubicin, 52, 165 Drive, ii, vi, 14, 63, 165, 176 Drug Interactions, 45, 70, 76, 124, 165 Drug Monitoring, 18, 21, 23, 29, 33, 38, 39, 40, 44, 45, 47, 48, 51, 56, 70, 73, 74, 75, 118, 143, 165 Duct, 165 Duodenum, 152, 165, 166, 176, 185, 196 Dyes, 147, 165, 171 Dyskinesia, 158, 165 E Eclampsia, 112, 165, 188 Edema, 112, 165, 169, 178, 188, 200

207

Effector, 145, 159, 165 Efficacy, 7, 8, 9, 13, 75, 92, 166 Elastic, 15, 166, 196 Electrocardiogram, 55, 166 Electrode, 100, 166 Electrolyte, 16, 81, 146, 166, 177, 180, 187, 195, 200 Electrons, 150, 152, 166, 176, 184, 191 Electrophoresis, 48, 166 Emboli, 166, 201 Embolism, 166, 176, 190, 201 Embolization, 166, 201 Embolus, 166, 175 Embryo, 147, 153, 166, 175, 183, 187 Emphysema, 36, 166 Enalapril, 4, 56, 166 Enalaprilat, 31, 166 Encapsulated, 101, 103, 108, 166, 178 Endogenous, 8, 12, 32, 33, 39, 47, 75, 110, 112, 165, 166, 189 Endometrium, 162, 166, 179 Endoscopic, 166, 180 Endothelial cell, 153, 166, 198 Endothelium, 167, 182 Endothelium-derived, 167, 182 Enhancer, 9, 167 Enteric-coated, 99, 167 Environmental Health, 128, 130, 167 Enzymatic, 154, 156, 159, 162, 167, 172, 185, 193 Enzyme Inhibitors, 60, 113, 167, 187 Ephedrine, 101, 167 Epithelial, 17, 75, 162, 167 Epithelial Cells, 17, 167 Epithelium, 167, 193 Epoprostenol, 167, 174 Erythrocytes, 18, 148, 153, 167, 172 Erythromycin, 13, 55, 85, 151, 158, 167 Esophagus, 167, 185, 196 Estrogen, 3, 167 Ethanol, 158, 167 Ethnic Groups, 6, 167 Evoke, 15, 167, 196 Excipient, 111, 167 Excitability, 149, 168, 190 Excitation, 151, 168, 182 Excrete, 150, 168, 177, 192 Exercise Test, 168 Exercise Tolerance, 4, 5, 168 Exocytosis, 168, 173 Exogenous, 8, 75, 145, 153, 155, 166, 168, 189, 199

Extracellular, 8, 16, 147, 160, 168, 195 Extracellular Space, 8, 168 Extracorporeal, 93, 168 Extraction, 76, 150, 168, 193 Extrarenal, 48, 168 F Family Planning, 129, 168 Fat, 148, 150, 152, 153, 156, 161, 166, 168, 177 Fatigue, 168, 172 Fatty acids, 146, 168, 189 Feces, 168, 196 Femoral, 155, 168 Femoral Artery, 155, 168 Fentanyl, 9, 168 Fetus, 112, 168, 169, 186, 200 Fibrillation, 26, 39, 58, 168 Fibrosis, 168, 169, 194 Filariasis, 163, 168 Fluorescence, 25, 78, 102, 106, 169 Fluorescence Polarization, 25, 78, 102, 106, 169 Fluorescence Polarization Immunoassay, 78, 106, 169 Fluorine, 113, 169 Fluoxetine, 3, 169 Flutter, 99, 169 Foetoplacental, 169, 183 Fold, 9, 14, 169, 179 Forearm, 153, 169 Formulary, 23, 169 Free Radicals, 150, 164, 169 Fructose, 169, 171 Furosemide, 31, 169 G Gallbladder, 145, 152, 169 Ganglia, 145, 152, 169, 182, 185, 197 Gas, 155, 157, 163, 169, 173, 182, 183, 200, 201 Gastric, 16, 147, 151, 169, 172, 183, 185 Gastric Acid, 147, 169, 183 Gastric Juices, 169, 185 Gastrin, 170, 173 Gastroenteritis, 154, 170 Gastrointestinal, 17, 103, 111, 154, 157, 167, 170, 194, 197 Gastrointestinal tract, 103, 157, 167, 170, 194 Gene, 17, 53, 82, 117, 153, 165, 170, 173 Genetic Engineering, 153, 158, 170 Genetics, 160, 165, 170 Genotype, 44, 170

208

Digoxin

Geriatric, 26, 59, 65, 66, 78, 170 Germ Cells, 170, 183, 184, 198 Gestation, 112, 170, 185, 186 Ginkgo biloba, 78, 170 Ginseng, 74, 75, 83, 84, 85, 86, 170 Gland, 145, 161, 170, 178, 184, 185, 189, 194, 196, 198 Glomerular, 170, 177, 192 Glucocorticoid, 170, 188 Glucose, 35, 38, 46, 151, 153, 163, 170, 171, 172, 175, 191, 194 Glucose Intolerance, 38, 163, 170 Glucose Oxidase, 46, 170 Glucose tolerance, 170, 171 Glucose Tolerance Test, 170, 171 Glycoprotein, 9, 13, 14, 16, 17, 18, 22, 32, 41, 42, 49, 50, 53, 65, 74, 75, 77, 82, 171, 186, 198 Glycoside, 82, 94, 97, 98, 100, 103, 105, 106, 114, 171, 184, 189, 194 Glycosidic, 92, 97, 156, 171 Gonadal, 171, 196 Governing Board, 171, 187 Gram-negative, 156, 171, 193 Gram-positive, 156, 171 Guanidine, 164, 171 Guanylate Cyclase, 171, 182, 183 H Haemodialysis, 54, 171 Haemoperfusion, 54, 171 Hair follicles, 171, 201 Half-Life, 171, 174 Haploid, 172, 187 Haptens, 93, 146, 172, 191 Headache, 154, 172 Health Services, 10, 172 Heart attack, 156, 172 Helminths, 172, 175 Hemodialysis, 59, 163, 172, 177 Hemoglobin, 51, 148, 167, 172 Hemolysis, 112, 172 Hepatic, 8, 9, 51, 65, 112, 146, 171, 172 Hepatocellular, 8, 172 Heredity, 170, 172 Heterogeneity, 146, 172 Heterogenic, 172 Heterogenous, 104, 172 Heterozygotes, 165, 172 Histamine, 64, 172, 173 Histamine Release, 64, 173 Histidine, 172, 173 Homeostasis, 8, 16, 173

Homogeneous, 44, 46, 100, 105, 173 Homologous, 8, 172, 173, 199 Homozygotes, 165, 173 Hormonal, 12, 17, 173 Hormone, 12, 30, 146, 161, 163, 170, 173, 175, 177, 179, 188, 198 Horseradish Peroxidase, 74, 173 Hybrid, 173 Hybridoma, 105, 173 Hydralazine, 58, 173 Hydrocodone, 3, 173 Hydrogen, 112, 145, 147, 152, 155, 163, 171, 173, 180, 184, 190 Hydrogen Peroxide, 171, 173 Hydrolysis, 153, 164, 173, 176, 190 Hydrophilic, 111, 173 Hydrophobic, 173, 176 Hydroxylation, 69, 80, 173 Hyperbilirubinemia, 78, 173, 176 Hyperkalaemia, 24, 174 Hypertension, 12, 58, 112, 115, 147, 148, 154, 156, 157, 166, 172, 174, 178, 180, 188, 200 Hyperthyroidism, 174, 188 Hypertrophy, 161, 174, 199 Hypnotic, 174, 180 Hypothalamic, 20, 35, 36, 37, 71, 76, 77, 174 Hypothalamus, 151, 174 Hypoxic, 50, 174 I Idiopathic, 174, 194 Iloprost, 48, 174 Imaging procedures, 174, 199 Immune response, 150, 161, 172, 174, 197, 201 Immune system, 105, 174, 175, 202 Immunity, 174 Immunoassay, 21, 23, 39, 44, 46, 48, 51, 57, 59, 72, 78, 92, 95, 96, 97, 99, 100, 105, 107, 109, 174 Immunogen, 92, 97, 174 Immunogenic, 92, 97, 108, 174, 191 Immunologic, 174 Immunology, 40, 146, 173, 174 Impairment, 11, 29, 165, 174, 188 Implantation, 160, 174, 183 In vitro, 12, 17, 18, 41, 48, 76, 80, 105, 174 In vivo, 9, 10, 13, 14, 16, 17, 64, 78, 92, 174 Incontinence, 167, 174 Incubated, 108, 174 Incubation, 98, 175

209

Indinavir, 9, 175 Induction, 9, 13, 148, 175, 191 Infancy, 52, 175 Infarction, 33, 157, 175, 176 Infections, 15, 149, 150, 151, 152, 168, 172, 175 Infestation, 101, 175 Inflammation, 146, 150, 154, 159, 168, 169, 170, 175, 179, 184, 187, 193, 200, 201 Inflammatory bowel disease, 36, 175 Infusion, 10, 175 Ingestion, 70, 72, 79, 171, 175, 179, 187 Inhalation, 145, 175, 187 Inorganic, 97, 107, 175 Inotropic, 39, 57, 89, 94, 95, 165, 175 Insight, 8, 16, 175 Insulin, 171, 175, 199 Intensive Care, 28, 33, 97, 175 Interstitial, 15, 37, 38, 168, 175, 192 Intestinal, 9, 13, 22, 31, 32, 49, 50, 74, 75, 156, 162, 171, 175 Intestine, 9, 152, 154, 175, 177 Intoxication, 18, 22, 29, 32, 33, 38, 39, 40, 46, 52, 53, 54, 70, 107, 176, 202 Intracellular, 17, 154, 176, 179, 183, 187, 189, 192 Intracellular Membranes, 176, 179 Intracranial Aneurysm, 157, 176 Intracranial Arteriosclerosis, 157, 176 Intrahepatic, 8, 176 Intravenous, 9, 32, 55, 65, 73, 112, 175, 176 Intrinsic, 146, 176 Involuntary, 152, 157, 168, 176, 181, 192 Ion Transport, 13, 176, 180 Ionization, 110, 176 Ions, 13, 152, 164, 166, 171, 173, 176, 180 Isoenzyme, 161, 176 Isoprenoid, 35, 176 Isosorbide Dinitrate, 20, 176 Itraconazole, 25, 50, 54, 176 J Jaundice, 173, 176 Jejunostomy, 43, 176 Jejunum, 176 K Kb, 14, 128, 177 Kidney Failure, 97, 177 Kidney Failure, Acute, 177 Kidney Failure, Chronic, 177 Kinetic, 14, 42, 177 L Lactation, 177, 183

Large Intestine, 175, 177, 192, 195 Lectin, 177, 179 Lenses, 110, 177 Lesion, 153, 177, 197, 199 Lethal, 14, 74, 79, 177 Leukemia, 14, 165, 177 Levofloxacin, 21, 177 Levothyroxine, 3, 177 Lidocaine, 39, 177 Ligaments, 161, 177 Ligands, 99, 177, 192 Linkage, 54, 92, 177, 185 Lipid, 114, 175, 177, 178, 180 Liposomal, 114, 177 Liposome, 100, 178 Lisinopril, 4, 178 Lithium, 118, 178 Loa, 163, 178 Localized, 147, 162, 166, 178, 187, 199 Locomotion, 178, 187 Luciferase, 94, 178 Lymph, 158, 166, 167, 178, 194 Lymph node, 178, 194 Lymphatic, 167, 178, 195, 196 Lymphatic system, 178, 196 Lymphedema, 15, 178 Lymphocytes, 9, 150, 178, 196, 202 Lymphoid, 149, 178 M Maintenance therapy, 21, 178 Malignant, 110, 150, 178, 179, 181 Malignant tumor, 179, 181 Malnutrition, 146, 154, 179 Manic, 178, 179 Mediate, 8, 165, 179 Mediator, 15, 50, 179, 194 Medical Errors, 10, 179 Medication Errors, 10, 11, 179 MEDLINE, 129, 179 Membrane Proteins, 8, 179, 190 Meningitis, 176, 179 Menopause, 179, 183, 188 Menstrual Cycle, 17, 179, 183, 188 Menstruation, 162, 179 Mental, iv, 4, 10, 128, 130, 157, 164, 168, 179, 183, 190, 194, 200 Mental Health, iv, 4, 128, 130, 179, 183 Mental Processes, 164, 179, 190 Mesenteric, 33, 37, 179 Mesentery, 179, 186 Metabolite, 21, 153, 164, 166, 179 Methanol, 76, 109, 179

210

Digoxin

Metoprolol, 22, 31, 180 Microbe, 180, 199 Microorganism, 159, 180, 185, 201 Microscopy, 173, 180 Microspheres, 114, 180 Midazolam, 9, 10, 13, 16, 180 Milk Thistle, 180, 195 Mineralocorticoids, 145, 180 Miosis, 180 Miotic, 10, 180 Mitotic, 180, 201 Modeling, 10, 45, 180 Modification, 19, 38, 98, 170, 180, 190 Modulator, 12, 65, 74, 180 Molecular, 8, 13, 16, 46, 129, 131, 148, 149, 153, 160, 169, 180, 199 Molecular Structure, 149, 180, 199 Monitor, 10, 97, 105, 162, 180, 183 Monoamine, 147, 163, 181 Monoclonal, 40, 80, 105, 181, 191 Monoclonal antibodies, 40, 105, 181 Mucosa, 17, 181 Multidrug resistance, 14, 30, 52, 181, 186 Multiple Myeloma, 37, 181 Muscle Contraction, 15, 181 Muscle relaxant, 181, 186 Muscle Spindles, 181, 186 Myeloma, 105, 173, 181 Myocardial Contraction, 99, 181 Myocardial infarction, 53, 115, 161, 181, 188, 201 Myocardial Ischemia, 55, 148, 181 Myocardium, 19, 111, 148, 181 Myopia, 181, 193 Myosin, 181 N Narcolepsy, 163, 167, 182 Narcotic, 168, 173, 182, 184 Natriuresis, 28, 148, 182 NCI, 1, 127, 158, 182 Necrosis, 157, 169, 175, 181, 182, 194 Nephrotoxic, 10, 182 Nervous System, 147, 151, 156, 179, 182, 185, 197 Neural, 15, 20, 147, 182, 193 Neuromuscular, 145, 182, 200 Neuromuscular Junction, 145, 182 Neuronal, 158, 182 Neurons, 169, 181, 182, 197 Neurotransmitter, 145, 154, 157, 165, 172, 182, 183, 197 Niacinamide, 182

Nicorandil, 65, 182 Nitric Oxide, 36, 182 Nitrogen, 104, 146, 148, 177, 183 Nitroglycerin, 176, 183 Norepinephrine, 145, 165, 167, 182, 183, 192 Normotensive, 31, 183 Nuclear, 151, 160, 166, 182, 183, 191 Nucleic acid, 183 Nucleus, 151, 152, 158, 162, 163, 178, 183, 188, 190 O Occupational Medicine, 10, 183 Oestrogen, 39, 183 Oliguria, 177, 183 Omeprazole, 3, 183 On-line, 24, 143, 183 Oocytes, 16, 183 Opsin, 183, 193 Osmotic, 146, 184, 194 Osteoporosis, 183, 184 Ouabain, 12, 14, 64, 94, 96, 99, 184, 197 Outpatient, 184 Ovary, 161, 183, 184, 187 Overdose, 76, 99, 118, 184 Ovum, 161, 162, 170, 184, 188 Oxidation, 92, 145, 150, 153, 162, 184 Oxidation-Reduction, 153, 184 Oxycodone, 9, 184 Oxygenator, 155, 184 P Pacemaker, 81, 184 Palliative, 9, 183, 184, 198 Pancreas, 145, 175, 184 Pancreatic, 184 Pancreatitis, 53, 184 Papain, 97, 185 Parasite, 101, 164, 185 Parasitic, 152, 162, 172, 175, 178, 185 Parietal, 183, 185, 186 Parotid, 185, 194 Paroxetine, 3, 185 Paroxysmal, 45, 148, 185 Particle, 178, 185, 196 Pathogen, 175, 185 Pathologic, 15, 95, 161, 173, 185 Pepsin, 185 Peptic, 37, 185 Peptic Ulcer, 37, 185 Peptide, 8, 110, 158, 185, 189, 190 Peptide Chain Elongation, 158, 185 Perception, 20, 71, 77, 185, 194

211

Perfusion, 152, 185 Perinatal, 9, 185 Peripheral Nervous System, 182, 185, 197 Peritoneal, 64, 185 Peritoneum, 179, 185, 186 Peroxide, 170, 186 P-Glycoprotein, 29, 186 Pharmaceutical Preparations, 103, 167, 186, 189 Pharmacodynamic, 10, 25, 39, 118, 186 Pharmacokinetic, 9, 11, 21, 25, 27, 32, 39, 42, 48, 50, 51, 80, 186 Pharmacologic, 13, 15, 148, 171, 186, 199 Pharmacotherapy, 26, 27, 30, 32, 34, 43, 186 Phenyl, 113, 164, 186 Phenytoin, 11, 118, 155, 186 Phosphorus, 154, 186 Phosphorylation, 14, 186 Physical Therapy, 15, 186 Physiologic, 146, 152, 171, 179, 186, 189, 191 Pigment, 152, 186, 193 Placenta, 14, 22, 41, 112, 169, 186, 188 Plants, 114, 146, 152, 155, 163, 164, 170, 171, 177, 183, 184, 186, 187, 194, 199 Plasma cells, 149, 181, 187 Plasma protein, 146, 187, 194 Plasmapheresis, 93, 187 Platelet Aggregation, 167, 174, 182, 187 Platelet Count, 112, 187 Platelets, 112, 182, 187, 194, 198 Pneumonia, 160, 187 Poisoning, 33, 56, 75, 82, 170, 176, 187 Pollen, 187, 190 Polyethylene, 106, 187 Polymorphism, 14, 53, 187 Polysaccharide, 150, 187 Potassium, 4, 12, 15, 21, 24, 48, 64, 67, 78, 94, 100, 146, 174, 180, 182, 187, 191 Practice Guidelines, 130, 187 Precipitation, 106, 188 Precursor, 12, 148, 150, 165, 167, 183, 188 Prednisolone, 188 Prednisone, 101, 188 Preeclampsia, 112, 188 Pre-eclamptic, 165, 188 Prevalence, 7, 188 Probe, 10, 13, 48, 171, 188 Probenecid, 47, 188 Procaine, 177, 188 Progesterone, 17, 77, 188, 196

Progression, 8, 148, 188 Progressive, 112, 158, 177, 182, 188, 192 Promoter, 17, 188 Propafenone, 26, 81, 120, 188 Prophase, 183, 188 Prophylaxis, 188, 201 Propranolol, 34, 188 Propylene Glycol, 106, 189 Proscillaridin, 81, 189 Prospective study, 21, 189 Prostaglandin, 148, 167, 189 Prostate, 183, 189 Protease, 9, 159, 175, 189, 193 Protease Inhibitors, 9, 189 Protective Agents, 154, 189 Protein Binding, 65, 78, 118, 189 Protein C, 16, 92, 102, 103, 107, 146, 147, 189 Protein S, 98, 114, 117, 153, 158, 167, 189 Proteinuria, 112, 181, 188, 189 Proteolytic, 159, 185, 190 Proton Pump, 183, 190 Protons, 173, 190, 191 Protozoa, 152, 160, 180, 190 Psychic, 179, 190, 194 Psychoactive, 190, 202 Psychology, 10, 164, 190 Psychotomimetic, 147, 163, 190 Public Policy, 129, 190 Publishing, 18, 190 Pulmonary, 104, 112, 153, 157, 161, 167, 168, 177, 190, 201 Pulmonary Artery, 153, 190, 201 Pulmonary Circulation, 104, 190 Pulmonary Edema, 112, 157, 177, 190 Pulmonary Embolism, 190, 201 Pulmonary hypertension, 161, 167, 190 Pulsation, 169, 190 Pulse, 100, 181, 190 Pupil, 164, 180, 190 Q Quality of Life, 4, 5, 28, 55, 190 Quercetin, 74, 79, 190 Quinidine, 18, 41, 45, 51, 52, 65, 66, 76, 80, 102, 190 Quinine, 190, 191 R Race, 163, 191 Racemic, 163, 191 Radiation, 148, 165, 169, 191 Radiation therapy, 165, 191

212

Digoxin

Radioactive, 108, 171, 173, 174, 176, 181, 183, 191 Radioactivity, 98, 191 Radioimmunoassay, 19, 48, 72, 79, 92, 94, 98, 108, 109, 191 Radioisotope, 191, 199 Randomized, 4, 5, 6, 52, 59, 166, 191 Reabsorption, 188, 191 Reaction Time, 108, 191 Reagent, 98, 99, 100, 104, 106, 157, 178, 191 Receptor, 12, 13, 18, 30, 39, 94, 114, 115, 150, 165, 191, 194 Receptors, Adrenergic, 163, 192 Recombinant, 16, 152, 192, 200 Rectum, 150, 154, 159, 169, 174, 175, 177, 189, 192 Recurrence, 34, 192 Reductase, 42, 192 Refer, 1, 159, 170, 178, 192, 199 Reflex, 15, 181, 192 Regeneration, 93, 192 Regimen, 10, 166, 186, 192 Relative risk, 145, 192 Reliability, 32, 192 Remission, 178, 192 Renal Artery, 64, 192 Renal failure, 11, 34, 107, 192 Renal tubular, 70, 81, 188, 192 Renin, 113, 148, 155, 192 Renin-Angiotensin System, 113, 148, 155, 192 Respiration, 155, 180, 193 Resuscitation, 33, 193 Retina, 160, 161, 181, 193, 201 Retinal, 112, 193, 201 Retinal Detachment, 112, 193 Retinol, 193 Reversion, 26, 156, 193 Rhamnose, 184, 193 Rheumatoid, 93, 193 Rhinitis, 167, 193 Rhodopsin, 184, 193 Ribose, 145, 193 Rigidity, 187, 193 Risk factor, 12, 56, 189, 192, 193 Ritonavir, 29, 193 Rods, 193 Rutin, 190, 194 S Saponins, 194, 196 Sarcoidosis, 37, 194 Schizoid, 194, 202

Schizophrenia, 194, 202 Schizotypal Personality Disorder, 194, 202 Screening, 12, 158, 194 Sebaceous, 194, 201 Secretion, 8, 38, 65, 74, 75, 172, 173, 177, 180, 183, 194 Secretory, 183, 194 Sedative, 159, 163, 180, 194 Seizures, 112, 155, 185, 186, 194 Semisynthetic, 147, 155, 156, 158, 184, 194 Serologic, 174, 194 Serotonin, 158, 169, 182, 185, 186, 194 Serum Albumin, 92, 100, 191, 194 Sex Characteristics, 148, 183, 195, 198 Shock, 45, 95, 156, 195, 199 Shunt, 93, 195 Side effect, 9, 93, 102, 109, 111, 114, 123, 145, 158, 165, 195, 199 Silicon, 107, 195 Silicon Dioxide, 195 Silymarin, 75, 180, 195 Skeletal, 15, 16, 23, 24, 35, 148, 157, 161, 181, 190, 195 Skeleton, 145, 189, 195 Skull, 195, 197 Small intestine, 165, 173, 175, 176, 195 Smooth muscle, 12, 94, 154, 172, 183, 192, 195, 197 Social Environment, 190, 195 Social Support, 10, 195 Sodium, 12, 21, 50, 73, 94, 111, 113, 118, 146, 149, 166, 167, 180, 182, 191, 195 Solid tumor, 165, 195 Solvent, 167, 179, 184, 189, 196 Sotalol, 52, 196 Sound wave, 160, 196 Specialist, 135, 164, 196 Species, 98, 99, 102, 155, 164, 170, 172, 173, 181, 185, 190, 191, 196, 197, 201, 202 Specificity, 8, 16, 17, 21, 92, 93, 146, 149, 196 Spinal cord, 156, 157, 182, 185, 192, 196, 197 Spleen, 105, 147, 173, 178, 194, 196 Stabilization, 186, 196 Steady state, 32, 47, 74, 196 Steroid, 13, 30, 92, 110, 152, 155, 161, 183, 194, 196 Stimulant, 101, 147, 154, 163, 172, 196 Stimulus, 160, 165, 166, 168, 191, 192, 196, 197, 198

213

Stomach, 145, 151, 167, 169, 170, 171, 173, 185, 195, 196 Stool, 18, 159, 174, 177, 196 Stress, 4, 10, 102, 104, 151, 156, 161, 170, 196 Striate, 161, 196 Stroke, 128, 155, 156, 196 Strontium, 107, 196 Strophanthins, 155, 197 Subclinical, 194, 197 Subcutaneous, 164, 165, 178, 197 Subliminal, 20, 197 Subspecies, 196, 197 Substance P, 108, 167, 179, 194, 197 Substrate, 8, 14, 17, 53, 167, 197 Sulfur, 113, 197 Suppression, 55, 57, 197 Supraventricular, 34, 52, 54, 58, 76, 103, 197 Sympathetic Nervous System, 113, 148, 151, 197 Sympathomimetic, 147, 163, 165, 183, 197 Symptomatic, 52, 115, 184, 197 Systemic, 12, 13, 14, 17, 104, 124, 147, 150, 153, 188, 191, 194, 197, 199, 200, 201 Systolic, 174, 197 T Tachycardia, 24, 34, 52, 54, 58, 71, 76, 99, 103, 197 Tardive, 158, 197 Temporal, 104, 197 Teratogenic, 164, 197 Testicular, 38, 198 Testis, 183, 198 Testosterone, 38, 192, 198 Theophylline, 87, 100, 118, 198 Therapeutics, 10, 21, 22, 25, 31, 32, 42, 49, 50, 51, 52, 53, 55, 75, 78, 80, 81, 124, 198 Thermal, 149, 164, 198 Threshold, 168, 174, 197, 198 Thrombin, 187, 189, 198 Thrombocytes, 187, 198 Thrombomodulin, 189, 198 Thrombosis, 25, 94, 176, 189, 196, 198 Thyroid, 174, 177, 198 Thyroid Gland, 174, 198 Thyroxine, 95, 146, 177, 198 Ticks, 175, 198 Tone, 12, 111, 183, 198 Tonic, 155, 156, 198 Tonicity, 172, 198 Tonus, 198

Topical, 167, 173, 185, 198 Torsion, 175, 199 Toxaemia, 188, 199 Toxic, iv, 6, 43, 92, 94, 97, 99, 100, 107, 111, 152, 155, 160, 162, 163, 174, 179, 182, 199 Toxicology, 33, 38, 43, 74, 130, 199 Toxin, 14, 101, 199 Toxoplasmosis, 151, 199 Trace element, 169, 195, 199 Tracer, 95, 102, 173, 199 Transfection, 153, 199 Translation, 167, 199 Translocating, 13, 199 Translocation, 13, 158, 167, 199 Transmitter, 145, 165, 179, 183, 199 Trauma, 152, 157, 172, 182, 185, 199 Trichloroacetic Acid, 102, 199 Tricuspid Atresia, 161, 199 Tricyclic, 87, 158, 199 Tunica, 181, 199 Type 2 diabetes, 38, 199 U Ulcer, 16, 199, 200 Ulceration, 185, 200 Uraemia, 185, 200 Uremia, 177, 192, 200 Ureters, 192, 200 Urethra, 189, 200 Uricosuric, 188, 200 Urinary, 157, 167, 174, 183, 200 Urine, 16, 18, 76, 98, 107, 112, 117, 150, 153, 161, 165, 171, 174, 177, 182, 183, 189, 200 Uterus, 161, 162, 166, 179, 188, 200 V Vagina, 163, 179, 200 Vaginal, 17, 200 Varicose, 15, 200 Varicose vein, 15, 200 Vascular, 12, 15, 110, 147, 154, 167, 175, 176, 182, 186, 198, 200 Vascular Resistance, 147, 200 Vasculitis, 185, 200 Vasoconstriction, 12, 200 Vasodilatation, 182, 200 Vasodilation, 101, 148, 166, 174, 182, 200 Vasodilator, 154, 165, 172, 173, 176, 200 VE, 7, 200 Vector, 14, 200 Vein, 93, 148, 150, 176, 183, 185, 200, 201 Venom, 56, 75, 82, 120, 200

214

Digoxin

Venous, 15, 150, 157, 182, 183, 187, 189, 199, 201 Venous blood, 157, 187, 201 Venous Thrombosis, 201 Ventricle, 104, 151, 161, 174, 190, 197, 199, 201 Ventricular, 13, 22, 24, 26, 43, 45, 58, 59, 71, 95, 147, 161, 188, 199, 201 Venules, 153, 154, 201 Verapamil, 22, 34, 41, 45, 59, 64, 65, 201 Veterinarians, 102, 201 Veterinary Medicine, 129, 201 Vinblastine, 75, 77, 201 Vinca Alkaloids, 201 Vincristine, 65, 74, 77, 201 Virulence, 151, 199, 201 Virus, 167, 170, 201

Visual Acuity, 177, 201 Vitreous, 193, 201 Vitreous Humor, 193, 201 Vitro, 17, 201 Vivo, 9, 13, 92, 201 Vulgaris, 94, 201 W Warfarin, 11, 26, 54, 87, 201 Warts, 199, 202 White blood cell, 149, 152, 174, 178, 181, 187, 202 Withdrawal, 53, 60, 61, 120, 202 X Xenograft, 149, 202 Z Zymogen, 189, 202

215

216

Digoxin