ATORVASTATIN 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 2003 by ICON Group International, Inc. Copyright 2003 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., 1960Atorvastatin: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-83752-X 1. Atorvastatin-Popular works. I. Title.
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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.
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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on atorvastatin. 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 ATORVASTATIN ........................................................................................ 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Atorvastatin .................................................................................. 4 E-Journals: PubMed Central ....................................................................................................... 17 The National Library of Medicine: PubMed ................................................................................ 17 CHAPTER 2. NUTRITION AND ATORVASTATIN .............................................................................. 67 Overview...................................................................................................................................... 67 Finding Nutrition Studies on Atorvastatin................................................................................. 67 Federal Resources on Nutrition ................................................................................................... 85 Additional Web Resources ........................................................................................................... 86 CHAPTER 3. ALTERNATIVE MEDICINE AND ATORVASTATIN ........................................................ 89 Overview...................................................................................................................................... 89 National Center for Complementary and Alternative Medicine.................................................. 89 Additional Web Resources ........................................................................................................... 91 General References ....................................................................................................................... 93 CHAPTER 4. CLINICAL TRIALS AND ATORVASTATIN ..................................................................... 95 Overview...................................................................................................................................... 95 Recent Trials on Atorvastatin...................................................................................................... 95 Keeping Current on Clinical Trials ............................................................................................. 96 CHAPTER 5. PATENTS ON ATORVASTATIN ..................................................................................... 99 Overview...................................................................................................................................... 99 Patents on Atorvastatin ............................................................................................................... 99 Patent Applications on Atorvastatin ......................................................................................... 106 Keeping Current ........................................................................................................................ 121 CHAPTER 6. PERIODICALS AND NEWS ON ATORVASTATIN ......................................................... 123 Overview.................................................................................................................................... 123 News Services and Press Releases.............................................................................................. 123 Academic Periodicals covering Atorvastatin ............................................................................. 127 CHAPTER 7. RESEARCHING MEDICATIONS .................................................................................. 129 Overview.................................................................................................................................... 129 U.S. Pharmacopeia..................................................................................................................... 129 Commercial Databases ............................................................................................................... 130 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 133 Overview.................................................................................................................................... 133 NIH Guidelines.......................................................................................................................... 133 NIH Databases........................................................................................................................... 135 Other Commercial Databases..................................................................................................... 138 APPENDIX B. PATIENT RESOURCES ............................................................................................... 139 Overview.................................................................................................................................... 139 Patient Guideline Sources.......................................................................................................... 139 Finding Associations.................................................................................................................. 141 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 143 Overview.................................................................................................................................... 143 Preparation................................................................................................................................. 143 Finding a Local Medical Library................................................................................................ 143 Medical Libraries in the U.S. and Canada ................................................................................. 143 ONLINE GLOSSARIES................................................................................................................ 149 Online Dictionary Directories ................................................................................................... 149
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ATORVASTATIN DICTIONARY.............................................................................................. 151 INDEX .............................................................................................................................................. 199
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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 atorvastatin 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 atorvastatin, 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 atorvastatin, 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 atorvastatin. 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 atorvastatin, 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 atorvastatin. 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 ATORVASTATIN Overview In this chapter, we will show you how to locate peer-reviewed references and studies on atorvastatin.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and atorvastatin, 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 “atorvastatin” (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: •
Aggressive Lipid Lowering Does Not Improve Endothelial Function in Type 2 Diabetes: The Diabetes Atorvastatin Lipid Intervention (DALI) Study: A Randomized, Double-Blind, Placebo-Controlled Trial Source: Diabetes Care. 25(7): 1211-1216. July 2002. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: Endothelial dysfunction is considered an important early marker of atherosclerosis (hardening of the arteries) and cardiovascular risk and is currently used as a surrogate end point for cardiovascular risk in clinical trials. Patients with type 2 diabetes show a characteristic dyslipidemia (abnormal blood fats, such as cholesterol). Aggressive lipid lowering might be an effective method to improve endothelial function
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in these patients. This article reports on a study of this hypothesis that featured 133 patients with type 2 diabetes without a history of cardiovascular disease. Patients were given atorvastatin (10 milligrams and 80 milligrams) during the study. Despite substantial lowering of all atherogenic lipid parameters, no improvement of endothelium-dependent vasodilation was found. The authors conclude that aggressive lipid lowering by administration of atorvastatin, resulting in substantial improvement of the lipid profile, did not reverse endothelial dysfunction. 1 figure. 2 tables. 42 references.
Federally Funded Research on Atorvastatin The U.S. Government supports a variety of research studies relating to atorvastatin. 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 atorvastatin. 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 atorvastatin. The following is typical of the type of information found when searching the CRISP database for atorvastatin: •
Project Title: ATORVASTATIN (CI-981) ADDED TO TROGLITAZONE IN TYPE II DIABETES MELLITUS Principal Investigator & Institution: Jacobs, Laurence S.; University of Rochester Orpa Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2001 Summary: The purpose of this study is to determine whether Atorvastatin treatment for hyperlipidemia can safaely be administered to Type II Diabetes Mellitus patients also taking Troglitazone. Liver enzymes changes and the effect of this combined therapy on triglyceride and other lipoprotein levels will be assessed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ATORVASTATIN AS COMPARED TO SIMVASTATIN WHEN USED TO CONTROL MIXED DY Principal Investigator & Institution: Friday, Karen E.; Tulane University of Louisiana New Orleans, La 70118 Timing: Fiscal Year 2001 Summary: This is a 54-week, open-label, randomized, parallel-group study of Atorvastatin compared to Simvastatin in mixed dyslipidemic patients with and without Type II diabetes mellitus. Patients with or without documented coronary heart disease
2
Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).
Studies
5
(CHD) and/or peripheral vascular disease will be eligible. Following dietary therapy, all patients will be randomly assigned to begin dosing at the starting dose of randomly assigned atorvastatin or simvastatin and titrate to NCEP LDL-C goal or to maximum approved doses. In addition, the study will assess the mean percent change from baseline in lipid fractions and apolipoprotein B and the proportion of patients who achieve NCEP LDL-C goals at the end of 54 weeks of treatment. Safety parameters assessed will be the percent of patients with persistent transaminase elevations, and the percent of patients developing myopathy, in addition to routine safety monitoring. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ATORVASTATIN AS SECONDARY PREVENTION OF CORONARY HEART DISEASE Principal Investigator & Institution: Buse, John B.; Associate Professor; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2001 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ATORVASTATIN, A PRENYLATION INHIBITOR IN ACUTE LEUKEMIA. Principal Investigator & Institution: Perez, Raymond P.; Medicine; Dartmouth College 11 Rope Ferry Rd. #6210 Hanover, Nh 03755 Timing: Fiscal Year 2002; Project Start 01-MAR-2002; Project End 28-FEB-2004 Summary: (provided by applicant): Ras proteins are critically involved in transformation, proliferation, and survival of malignant cells, including blasts from patients with acute leukemia and myelodysplasia. Ras proteins require posttranslational modification (prenylation) for activity, as do several other critical proteins. Prenylation involves addition of 15- (farnesyl) or 20-carbon (geranylgeranyl) groups, intermediates in de-novo cholesterol biosynthesis, to specific CAAX motifs near the Cterminus. Specific inhibitors of enzymes that catalyze prenylation, farnesyltransferase (FT) and geranylgeranyltransferase-l and -II (GGT-1, GGT-II), are currently in clinical trials or preclinical models. Efficacy of such inhibitors may be limited by the potential for some Ras proteins to be prenylated by either FT or GGT-1; inhibition of one enzyme may be circumvented by the other transferase. An alternative therapeutic strategy involves HGM-CoA reductase inhibitors (statins), such as atorvastatin, which block synthesis of both farnesyl and geranylgeranyl groups. Statins inhibit prenylation and proliferation of human leukemia, and other malignant, cell lines in-vitro. The long-range objective of our research is to determine the clinical utility of inhibiting prenylation in patients with acute leukemia, and myelodysplasia. The proposed investigations are an initial test of the hypothesis that atorvastatin inhibits Ras prenylation in malignant myeloblasts at clinically tolerable doses. Two specific aims are proposed: (1.) To define the maximal tolerated dose, pharmacokinetics, and pharmacodymamics of atorvostatin in patients with acute leukemias or myelodysplasia, in an accelerated-titration phase-I trial; (2.) To determine whether inhibition of prenylation of prelamin A in buccal mucosa, a surrogate tissue, correlates with inhibition of Ras prenylation in leukemic cells. Pharmacodynamic endpoints in specific aim 1 include effects of atorvastatin on clinical / laboratory toxicities, Ras prenylation, HMG-CoA reductase activity, and mevalonate levels. In specific aim 2, inhibition of prelamin A prenylation is compared against inhibition of prenylation in tumor tissue, as initial validation of the surrogate
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endpoint. The proposed investigations, the first clinical trial of atorvastatin in cancer patients, lay groundwork for subsequent proof-of-principle and phase II trials in cancer patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CAROTID PLAQUE COMPOSITION BY MRI DURING LIPIDLOWERING Principal Investigator & Institution: Zhao, Xue-Qiao; Medicine; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2001; Project Start 01-FEB-2000; Project End 31-JAN-2004 Summary: The hypothesis of lipid depletion for plaque and clinical stability has been established based on observations from animal studies, the relation between human coronary plaque features and unstable clinical episodes, and angiographic regression and clinical event reduction with lipid-lowering therapy. However, the effect of lipidlowering therapy on human atherosclerotic plaque composition in vivo has not been possible, to date. Magnetic resonance imaging (MRI) is ideal for longitudinal studies of atherosclerotic arteries because it is noninvasive and is superior to other imaging modalities in discriminating tissue contrast. Encouraging results from our pilot study show that prolonged intensive lipid-lowering therapy appears to be associated with a decreased lipid composition in the plaque, which is considered to predict greater plaque stability. We propose to perform carotid MRI studies in 60 CAD patients with a family history of cardiovascular disease and ApoB equal to or greater than 125 mg/dl. These patients will be randomized to triple lipid-lowering therapy (atorvastatin 10-40 mg/day, niacin 2-3 gm/day, and colestipol 20 gm/day) or to mono-statin therapy (atorvastatin 20-80 mg/day), and will undergo MRI examination of both carotid arteries annually for three years, a total of 4 examinations. We will: 1) test the hypothesis that intensive lipidlowering therapy depletes plaque lipid composition identified by MRI in carotid arteries in CAD patients and examine the relationship between depletion of plaque lipid and other plaque components and plaque regression; 2) determine the time- course of atherosclerotic plaque lipid depletion during lipid- lowering by assessing serial carotid MRI examinations; 3) continue the development of this noninvasive approach to characterize human carotid atherosclerotic plaque composition in vivo by MRI. This study employs a state-of-the art technique to assess both the magnitude and mechanisms of benefit of lipid- lowering. It will be one of the first studies to examine the effects of lipid-lowering therapy on human atherosclerotic plaques in vivo and will provide novel insights into our understanding of atherosclerotic plaque pathology and the mechanisms of lipid-lowering therapy preventing ischemic events. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CLINICAL CENTER Principal Investigator & Institution: Wofsy, David; Professor; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2008 Summary: The University of California, San Francisco (UCSF) conducts clinical trials in a wide range of autoimmune diseases. This proposal focuses on three of these diseases (SLE, MS, and IDDM), and presents detailed descriptions of two potential clinical trials that demonstrate our interests and our ability to develop collaborative multicenter clinical trials for patients with autoimmune diseases. The two proposed clinical trials are: Protocol 1: Treatment of lupus nephritis with CTLA4Ig, a fusion protein that
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inhibits T cell costimulation via the CD28 pathway. This trial represents the culmination of a comprehensive bench-to-bedside research program conducted at UCSF by the PI of the Clinical Center and the PI of Project 2 in this application. The proposed trial will determine: (i) whether CTLA4Ig augments the benefit of cyclophosphamide (CTX) therapy in patients with lupus nephritis; (ii) whether CTLA4Ig can minimize the duration of therapy with CTX; (iii) whether combined therapy with CTX and CTLA4Ig can eliminate the need for maintenance therapy (induce 'tolerance'); and (iv) whether CTLA4Ig is better tolerated/safer than CTX. Protocol 2: Treatment with atorvastatin to prevent progression to MS after a clinically isolated first attack of CNS demyelination. This trial also represents a true bench-to-bedside collaboration among basic and clinical scientists involved in this application. It arose from studies by Dr. Scott Zamvil at UCSF, demonstrating that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors ('statins') can prevent or reverse paralysis in murine models for MS. The proposed trial will determine whether atorvastatin can prevent progression to MS in patients at high risk for the developing the disease. Although it is not represented in this application by a detailed protocol, the Diabetes program at UCSF also has a very strong clinical trials component. The short-term goal of our clinical trials program in diabetes is to extend recent studies of anti-CD3 therapy to determine the potential of this approach to treat early IDDM and/or to prevent IDDM in people at high risk for the disease. We also are conducting trials to examine new strategies to facilitate islet transplantation. In addition to our studies in SLE, MS, and IDDM, investigators affiliated with our Center are currently conducting clinical trials in numerous other autoimmune diseases, including rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, Sjogren syndrome, scleroderma, and Wegener's granulomatosis. This breadth of interests and experience at UCSF provides evidence of our ability to contribute across a broad range of potential ACE trials. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CLINICAL MORPHOLOGY
IMPLICATIONS
OF
PERIPHERAL
PLAQUE
Principal Investigator & Institution: Ouriel, Kenneth; Surgery; Cleveland Clinic Lerner Col/Med-Cwru Cleveland, Oh 44195 Timing: Fiscal Year 2003; Project Start 22-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): Peripheral arterial disease (PAD) is found in almost 20% of the population aged 55 and older. It is responsible for incapacitating symptoms of leg pain when walking, culminating in amputation in a small proportion of patients. Further, the presence of PAD is a strong marker for future cardiovascular events such as myocardial infarction and stroke. Despite the clinical significance of PAD, it is under diagnosed and its pathobiology remains ill defined. While imaging studies play an integral role in the study of most disease processes, angiography, standard ultrasound examination, and even magnetic resonance imaging do not provide adequate resolution of the arterial wall to quantify and characterize the extent of vascular wall abnormalities or to track changes over time. Intravascular ultrasound (IVUS) technology is associated with spatial resolution of 80-100 fm radially and 150-200 fm circumferentially. As such, IVUS appears ideally suited to the quantification of vascular wall changes. Our group has studied IVUS in the characterization of coronary artery plaque morphology, correlating clinical signs and symptoms with atheroma burden and content. We propose similar studies in the peripheral arterial bed, quantifying the amount and composition of lower extremity arterial atheroma and relating these findings to the patients' clinical presentation and subsequent course. This goal will be accomplished through the
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completion of three separate but concurrent studies: (1) Histologic sections of fresh arterial segments from cadaver limbs and amputation specimens will be correlated with IVUS-derived radiofrequency data to quantify arterial plaque burden and composition (calcium, collagen, fibro-lipidic and necrotic components). (2) Patients undergoing standard lower extremity angiography for PAD will be studied with IVUS at the same sitting. IVUS findings will be correlated with demographic factors (age, gender, race) and symptom severity (claudication, rest pain, tissue loss). Patients will be followed for up to five years, and the occurrence of ischemic events (worsening of leg ischemia, need for intervention and re-intervention, and distant complications such as Mi and stroke) will be reconciled with the arterial wall content at the baseline examination. (3) A randomized, blinded clinical trial of high-dose atorvastatin vs. placebo will be performed in patients with intermittent claudication, based on our hypothesis that statin therapy will result in stabilization or regression of femoral artery plaque, differences best assessed with high resolution imaging studies. IVUS data will be collected at baseline and at 24 months. The primary endpoint will be the change in femoral arterial plaque volume; baseline arterial wall parameters will be assessed in the subgroup of stain responders vs. non-responders. The completion of these three investigations should yield a validated, high resolution, real time imaging study with which to assess risk and base treatment decisions in patients with PAD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CLINICAL UTILITY OF ENDOTHELIAL FUNCTION IN PAD Principal Investigator & Institution: Vita, Joseph A.; Associate Professor; Boston Medical Center Gambro Bldg, 2Nd Fl, 660 Harrison Ave, Ste a Boston, Ma 02118 Timing: Fiscal Year 2003; Project Start 22-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): Peripheral arterial disease (PAD) produces considerable morbidity and mortality, and the precise factors that determine disease progression and the responses to therapy remain largely unknown, In addition to their risk for critical limb ischemia or graft failure, PAD patients also have markedly increased risk for coronary heart disease, particularly during the stress of vascular surgery, It is clear that new approaches are needed for optimal risk assessment and therapy. Targeting endothelial function represents a major new departure from traditional methods for assessing cardiovascular disease risk. The central hypothesis of this proposal is that endothelial dysfunction is a critical mediator of both PAD and coronary heart disease events and measuring endothelial function will enhance both the risk assessment and therapy in PAD patients. Recent studies by the applicants strongly support this contention and establish the prognostic value of endothelial dysfunction in PAD patients undergoing vascular surgery. A key unresolved question is whether reversing endothelial dysfunction will directly reduce risk. This finding would more firmly establish endothelial dysfunction as a mediator of both PAD and coronary heart disease risk and further validate its clinical utility. We propose the following specific aims: 1. To determine whether reversing endothelial dysfunction ameliorates perioperative risk in PAD patients. Patients referred for elective vascular surgery will be treated with high dose atorvastatin (80 mg/day), ascorbic acid (500 mg/day), or placebo in a randomized, double blind, fashion beginning a month prior to surgery and continuing for a month after surgery. Non-invasive assessment of vascular function will be performed at baseline and immediately prior to surgery. Patients will be monitored for cardiovascular events (cardiac death, myocardial infarction, unstable angina, and stroke) in the 30-day postoperative period. The goal is to determine whether improvement in vascular function independently predicts outcome (irrespective of
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which treatment produces the improvement). 2. To determine whether endothelial dysfunction predicts long-term (2-year) PAD and coronary heart disease risk in PAD patients. 3. To determine whether systemic markers of oxidative stress and inflammation relate to endothelial dysfunction and long-term PAD and coronary heart disease risk. This work will provide novel information about the pathogenesis and management of PAD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CORONARY VASCULAR RESPONSE TO ISCHEMIA Principal Investigator & Institution: Bache, Robert J.; Professor of Medicine; Medicine; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2003; Project Start 01-JUL-1992; Project End 30-NOV-2007 Summary: (provided by applicant): The studies in this proposal will examine responses of the coronary vessels to myocardial ischemia, and determine whether alterations of nitric oxide (NO) or superoxide (O2-) influence vascular or myocardial responses in ischemic regions. Studies will be performed in chronically instrumented dogs in which coronary artery blood flow is measured with a Doppler flowmeter while regional systolic wall thickening is assessed with ultrasonic microcrystals. Myocardial perfusion is measured with microspheres; aortic and coronary venous catheters will allow measurements of coronary NO production. Three different groups of studies are planned. The first group will examine collateral vessel development in response to five daily 2-minute coronary artery occlusions; collateral development will be assessed from blood flow measurements obtained by administering microspheres during occlusion. Myocardial interstitial fluid will be collected using a chronically implanted catheter for measurement of vascular endothelial growth factor, NO metabolites and mitogenic activity in cultured endothelial and smooth muscle cells. Since NO is an important mediator for collateral vessel growth, and since superoxide (O2-) produced during ischemia and reoxygenation consumes NO, a study will determine whether scavenging O2- with a superoxide dismutase (SOD) mimetic can augment collateral growth. Since HMG CoA reductase inhibitors increase NO bioavailability in cultured endothelial cells, another study will determine whether the HMG CoA reductase inhibitor atorvastastin can augment collateral vessel development. A second group of studies will examine mechanisms responsible for endothelial dysfunction in collateral vessels and microvessels perfused through collateral channels. In vivo and in vitro studies will determine whether NO production is decreased and/or O2- production increased in coronary microvessels in collateral-dependent regions. The role of O2- will be examined by determining whether the SOD mimetic can improve endothelial function in microvessels perfused through collateral channels. A final group of studies will examine bioenergetic alterations in myocardium perfused through collateral channels. These studies will determine whether viable collateral-dependent myocardium with persistent contractile dysfunction ("hibernating myocardium") demonstrates a unique pattern of high energy phosphate (HEP) content at rest or during stress different from ischemic or stunned myocardium. Interrogation of myocardial deoxymyoglobin content will demonstrate whether contractile abnormalities in collateralized myocardium at rest or during catecholamine-induced stress are the result of oxygen insufficiency. A final study will examine the influence of NO on the energy supply/demand relationship in collateralized myocardium. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: EFFECT OF PRAVASTATIN AND ATORVASTATIN ON COENZYME Q10 Principal Investigator & Institution: Bleske, Barry E.; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 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: HYPOLIPIDEMIC THERAPY WITH ATORVASTATIN IN NIDDM Principal Investigator & Institution: Gerich, John E.; Professor of Medicine; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 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: INFLAMMATION AND INSULIN RESISTANCE IN PAD Principal Investigator & Institution: Creager, Mark A.; Associate Professor of Medicine; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 22-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): Patients with peripheral arterial disease (PAD) frequently have functional limitations and symptoms of claudication that impact adversely on their quality of life. Many progress to critical limb ischemia requiring revascularization. Vascular inflammation and insulin resistance are two important and interdependent conditions that are associated with atherosclerosis. Moreover, both inflammation and insulin resistance cause abnormalities in vascular function and insulin resistance interferes with skeletal muscle metabolism. As such, inflammation and insulin resistance provide attractive targets for therapy that could potentially ameliorate the development of symptomatic PAD or improve the function and clinical outcomes of patients with PAD. Accordingly, the applicants propose three specific aims to determine whether inflammation and insulin resistance contribute to the functional and clinical consequences of PAD. First, a prospective, nested, case-control evaluation will be performed to test the hypothesis that baseline plasma levels of inflammatory cytokines (e.g. interleukin (IL)-4, IL-6, IL-18, macrophage inhibiting cytokine-1, CD 40 ligand) among healthy men are associated with the development of future symptomatic PAD. Second, to test the hypothesis that inflammation and insulin resistance contribute to reduced walking distance in patients with intermittent claudication by impairing vascular reactivity and skeletal muscle metabolic function, plasma markers of inflammation and insulin resistance, endothelium-dependent and independent vasodilation (by vascular ultrasonography) and skeletal muscle glucose utilization (by [18F] FDG positron emission tomography) will be measured before and after 12 weeks of treatment with rosiglitazone, atorvastatin or placebo in a 2x2 factorial design protocol. Third, to test the hypothesis that inflammation and insulin resistance are associated with the incidence and progression of vein graft disease in patients undergoing lower extremity vein bypass, functional and morphologic changes in vein grafts (measured by ultrasound and magnetic resonance imaging) will be assessed and related to inflammation and insulin resistance and to a composite clinical outcome of graft occlusion, re-intervention or major amputation. It is anticipated that the findings
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from this investigation will uncover novel pathophysiologic mechanisms and foster a new paradigm for the treatment of PAD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INTERACTIONS BETWEEN PROTEASE INHIBITORS/ LIPID LOWERING Principal Investigator & Institution: Blaschke, Terrence F.; Professor; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2001 Summary: The purpose of this study was to determine whether HIV protease inhibitors affected the ability of the body to eliminate several drugs used to treat elevated cholesterol concentrations, since elevated cholesterol is one of the side effects of HIV treatment. The study was carried out in healthy volunteers who received a "statin" drug for several days, followed by a protease inhibitor (PI) combination, ritonavir and saquinavir, and finally both statin and PIs given together. Blood was taken to measure drug concentrations of the statin while administered alone and then again while given with the PIs. Three different statins were investigated: simvastatin, pravastatin and atorvastatin. This was a multicenter study done at several sites throughout the US, including Stanford. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MELANOMA CHEMOPREVENTION Principal Investigator & Institution: Dellavalle, Robert P.; Dermatology; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2007 Summary: (provided by applicant): The incidence of cutaneous malignant melanoma is rising faster than any other cancer in the US. 1 in 74 Americans will develop melanoma, more than 45,000 cases will be diagnosed, and more than 7,500 Americans will die from melanoma this year. Effective prevention of melanoma will not only save lives, but will also decrease the estimated one billion dollars spent annually treating melanoma in the US. There is currently no recognized chemoprevention for melanoma. Two large, randomized, placebo-controlled clinical trials, the VA-HIT Study utilizing gemfibrozil, and the AFCAPS Study utilizing lovastatin, have each reported an association of lipidlowering medication therapy with statistically significant lower melanoma incidence rates. Lovastatin inhibits melanoma cell growth in tissue culture, and mice Jed lovastatin develop lower lung metastases following tail vein injection with mouse B16 melanoma cells. More recently low concentrations of atorvastatin have been reported to specifically induce apoptosis and inhibit migration of human A375 melanoma cells but not cultured melanocytes. To investigate the unconventional hypothesis that lipid-lowering medications might prevent melanoma, a case-control study will be conducted utilizing Veterans Administration (VA) databases to answer the following question: Do persons who have developed cutaneous malignant melanoma have a history of less lipidlowering medication exposure than persons who are spared the disease? The answer to this question will help determine whether more expensive and labor intensive randomized prospective clinical trials of potentially teratogenic lipid-lowering medications should be initiated in persons at high risk of developing melanoma. Robert Dellavalle, MD, Ph.D., is an Assistant Professor of Dermatology at the University of Colorado Health Sciences Center and a staff dermatologist at the Denver VA medical center He is committed to a career in academic dermatology and public health. His
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current career goals are completing a Masters of Science in Public Health and becoming an independent researcher in skin cancer prevention and control. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MODULATION OF ALZHEIMER'S AMYLOIDOSIS BY STATINS Principal Investigator & Institution: Petanceska, Suzana S.; Assistant Professor; Nathan S. Kline Institute for Psych Res Psychiatric Research Orangeburg, Ny 10962 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2006 Summary: (provided by applicant): Cerebral accumulation of Amyloid beta (Abeta) peptides is an early event in establishing of Alzheimer's disease (AD) pathology. Based on the epidemiological evidence pointing to a link between cholesterol metabolism and AD and the numerous laboratory studies implicating cholesterol in the process of Abeta production and accumulation, it is now believed that cholesterol-lowering therapies will be of value as disease modifying agents. Several epidemiological studies revealed that statin use for the treatment of coronary arterial disease is associated with a decreased prevalence or a decreased risk of developing AD. The major objectives of this proposal are: to test the ability of different statins to delay the onset or retard the progression of brain Abeta deposition in the PSAPP transgenic mouse model of Alzheimer's amyloidosis, and to investigate the mechanisms by which statin treatment modulates brain Abeta accumulation. Our goal is to examine how the lipid-lowering as well as the anti-inflammatory/immunomodulatory activities of statins contribute to their effect on brain Abeta accumulation. To this end we will employ in vivo experimental paradigms using the PSAPP transgenic mouse model of Alzheimer's amyloidosis, as well as in vitro experimental paradigms using microglial and neuronal cultures. In the first specific aim we will compare the relative efficacy with which statins with different BBB permeability attenuate early as well as advanced Abeta deposition. We will then examine how statin treatments modulate APP processing and ApoE expression in brain (specific aim 2). Finally, we will evaluate the effects of statins on the inflammatory response in brain in the context of different paradigms of microglial activation and we will test their ability to prevent or attenuate Abeta-induced microglial neurotoxicity (specific aim 3). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NITRIC OXIDE METABOLISM IN STATIN-TREATED PEDIATRIC SLE Principal Investigator & Institution: Levesque, Marc C.; Assistant Professor; Medicine; Duke University Durham, Nc 27706 Timing: Fiscal Year 2003; Project Start 24-SEP-2003; Project End 30-JUN-2007 Summary: (provided by applicant): Systemic lupus erythematosus (SLE) is characterized by accelerated atherosclerosis. Macrophage-mediated vascular inflammation and endothelial dysfunction play important roles in the pathogenesis of atherosclerosis. Atherosclerotic lesions and the endothelium of SLE patients are characterized by increased expression of nitric oxide (NO) and the inducible isoform of nitric oxide synthase (NOS2). In contrast, endothelial dysfunction is characterized by diminished arterial vasodilation due to decreases in the activity of the endothelial isoform of NOS (NOS3). In animal models, the development of atherosclerosis is diminished in NOS2 deficient animals and is accelerated in NOS3 deficient animals. We believe that overexpression of endothelial and macrophage NOS2 in SLE patients leads to accelerated atherosclerosis, and over-expression of NOS2 may inhibit endothelial NOS3 activity and induce endothelial dysfunction. Statin therapy slows the progression of
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atherosclerosis and is associated with reductions in inflammation, including reductions in systemic levels of NO metabolites and NOS2 expression. In contrast, improvements in endothelial function with statin therapy are associated with increases in NOS3-mediated NO production. Because NOS2 produces quantitatively greater amounts of NO than NOS3, we believe that statin therapy in SLE patients will be associated with reductions in systemic NO metabolite levels and with reductions in endothelial and macrophage NOS2 expression. Previous studies indicated an association of NOS2 and NOS3 polymorphisms with systemic NO metabolite levels and vascular disease. Therefore, we believe that NOS2 and NOS3 polymorphisms are associated with accelerated atherosclerosis in SLE. The careful clinical measures of SLE disease activity and radiologic measures of atherosclerosis progression that will be performed as part of the Atherosclerotic Prevention in Pediatric Lupus Erythematosus (APPLE) study, provide an excellent opportunity to understand the relationship between measures of NO metabolism, progression of atherosclerosis and statin therapy in SLE patients. The APPLE trial is an NIH funded study that will determine the effect of prospectively treating 280 pediatric SLE patients with statin therapy on the progression of atherosclerosis. In addition to our proposed measures of NO metabolism in APPLE trial participants, one of the strengths of this application is our proposal to collect genetic information on the parents of pediatric SLE patients. This information will allow us to estimate haplotype relationships with greater precision and conduct genetic association tests that are robust to population substructure. In addition, these DNA samples will constitute an important resource for future genetic analyses of pediatric SLE. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PHARMACOGENETICS NETWORK FOR CARDIOVASCULAR RISK THERAPY Principal Investigator & Institution: Krauss, Ronald M.; Senior Medical Scientist; Division of Life Sciences; University of Calif-Lawrenc Berkeley Lab Lawrence Berkeley National Laboratory Berkeley, Ca 94720 Timing: Fiscal Year 2001; Project Start 27-SEP-2001; Project End 31-JUL-2002 Summary: (provided by applicant): The goal of this Pharmacogenetics Research Group is to identify common gene variants that contribute to interindividual differences in response to drugs used to reduce risk for cardiovascular disease (CVD). The Group comprises a multidisciplinary team of investigators with expertise in lipoprotein metabolism and blood pressure regulation; genomics and related computational methodology; clinical trials; human genetics and genetic epidemiology; transgenic mouse models, and database management and biostatistics. For the present study, the drugs chosen are atorvastatin, an HMG CoA reductase inhibitor that lowers plasma lipid levels, and ramipril, an ACE inhibitor that lowers blood pressure. Candidate genes are those with products in metabolic pathways that are potential targets of these drugs. DNA sequence variations in 50 genes will be determined in 24 Caucasians and 24 African-Americans, two ethnic groups with differing degrees of sequence diversity. Based on patterns of single nucleotide polymorphisms (SNPs), haplotypes will be constructed for each gene in both ethnic groups, and groups of SNP genotypes will be identified that are characteristic for the 2-4 most common haplotypes in each gene, present in at least 10 percent of the population. Haplotypes for genes related to atorvastatin effects (27 genes) will be determined in 600 individuals (300 from each ethnic group) who will receive 10 mg/day of this drug for 8 weeks. Haplotypes for genes related to ramipril effects (23 genes) will be determined in 600 individuals (300 from each ethnic group) who will receive 10 mg/day of this drug for 12 weeks. Detailed
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measurements of phenotypes related to lipoprotein and blood pressure regulation will be performed in the two respective cohorts, and associations will be sought with each of the respective candidate haplotypes. Functional effects of specific sequence variants will be tested in appropriate transgenic mouse models. Future studies will corroborate positive findings using samples from large ongoing clinical endpoint trials of atorvastatin and ACE inhibitor therapy. Data will be transmitted to the Pharmacogenetics Knowledge Base and other genomic databases. The findings will advance our fundamental understanding of the roles of specific genes and their variants in modulating biologic pathways of importance in the pathogenesis and management of CVD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PROTEASE INHIBITOR RELATED DYSLIPIDEMIA Principal Investigator & Institution: Wanke, Christine A.; Associate Professor; Family Medicine & Cmty Health; Tufts University Boston Boston, Ma 02111 Timing: Fiscal Year 2001; Project Start 12-JUL-2000; Project End 30-JUN-2005 Summary: Protease inhibitors are used as therapy in HIV patients and have been reported to cause elevations in plasma triglycerides, cholesterol, and glucose, and rarely to induce severe hypertriglyceridemia, pancreatitis, and diabetes mellitus with insulin resistance, excess fat deposition, and lipodystrophy. Our aims are to measure fasting Serum cholesterol (C), triglyceride (TG), remnant lipoprotein (RLP) C and TG, low density lipoprotein (LDL) C, high density lipoprotein C, lipoprotein(a), apolipoproteins A-I and B, apo E genotype, homocysteine, free fatty acids, glucose, insulin, and blood pressure. We will also assess smoking status, carotid artery wall thickness by ultrasound, and coronary artery calcification by computerized tomography in our prospective cohort of 400 HIV patients whose nutritional status is being evaluated and who are taking a variety of antiviral agents including protease inhibitors. Comparisons will be made on and off inhibitors and also longitudinally, and with controls. Our comparison group are participants in the Framingham Offspring Study who have had all the same parameters measured (n=3250). HIV patients who become hyperlipidemic on protease inhibitors will be treated with either gemfibrozil or atorvastatin. We will also examine the effects of protease inhibition in Hep G2 and CaCo2 cells with or without supplementation with fatty acids and cholesterol on lipoprotein assembly and secretion and apolipoprotein, LDL receptor, and microsomal transfer protein (MTP) gene expression. The effects of protease inhibition on lipoprotein metabolism and aortic foam cell formation will also be assessed in F1B hamsters on chow and on diets high in cholesterol and saturated fat. In addition, using a primed constant infusion in the constantly fed state and deuterated leucine, the secretion and catabolism of apoB-48 and apoB-100 within lipoproteins will be determined by GC/MS analysis and multicompartmental modeling in the presence or absence of protease inhibition with ritonavir in 10 males and 10 female HIV patients. We will test the following hypothesis: 1) protease inhibitors increase triglyceride and cholesterol by increasing RLP; 2) elevated RLP leads to increased carotid wall thickness and coronary calcification; 3) these increases can be ameliorated with diet, gemfibrozil and/or atorvastatin treatment; 4) in cell culture these RLP increases are elated to enhanced secretion of apo B-100 due to less intracellular degradation, and excess cellular lipid content; 5) in hamsters there are increased RLP in serum in animals on the atherogenic diet, especially with protease inhibition, and this leads to increased aortic foam cell formation; 6) in humans protease inhibition causes increased triglyceride-rich lipoprotein apo B-100 secretion. This research should define the nature of the problem, its mechanism, and methods for
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treatment wit regard to the hyperlipidemia induced by protease inhibitors in HIV patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PROTEASE INHIBITORS AND LIPID LOWERING AGENTS Principal Investigator & Institution: Lertora, Juan J L.; Professor and Head of Medical Pharmacolo; Tulane University of Louisiana New Orleans, La 70118 Timing: Fiscal Year 2001 Summary: Lipid metabolism disorders associated with protease inhibitor (PI) therapy is of growing concern and statin compounds such as simvastatin, pravastatin, and atorvastatin are increasingly being prescribed in persons taking PI-based potent antiretroviral therapy. It is important to determine whether there are significant drugdrug interactions between the statin compounds and protease inhibitors. The objectives of this study are to investigate the effect of ritonavir and saquinavir on the pharmacokinetics of pravastatin, simvastatin, and atorvastatin and to evaluate the effect of pravastatin on the disposition of nelfinavir and its M8 metabolite. This trial will be conducted in an HIV-uninfected population because of the concern about developing drug resistance in persons taking protease inhibitor monotherapy. To meet the goals of objective one, 14 evaluable subjects for each cohort of Arm A will be stabilized on a fixed regimen of pravastatin, simvastatin, or atorvastatin for four days. A baseline PK evaluation of pravastatin (or simvastatin or atorvastatin) will be completed on day 4. Pravastatin (or simvastatin or atorvastatin) dosing will cease following the day 4 dose and PK evaluation. On day 5, a ritonavir and saquinavir combination regimen will be initiated and continued through day 18 of the study. Pravastatin (or simvastatin or atorvastatin) dosing will resume on day 15 and continue through day 18. A repeat PK evaluation of pravastatin (or simvastatin or atorvastatin) in the context of combination therapy will be carried out on day 18. For objective two, a two-week regimen of nelfinavir will be initiated in 14 evaluable subjects participating in Arm B. On day 14, a baseline PK profile of nelfinavir and its M8 metabolite will be carried out. Pravastatin will then be added to this regimen for study days 15 to 18. On day 18, a repeat PK evaluation of nelfinavir and the M8 metabolite will be carried out in the context of combination therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SIMVASTATIN & ATORVASTATIN IN PT W/ TYPE II DIABETES MELLITUS & HYPER Principal Investigator & Institution: Crouse, John; Wake Forest University 2240 Reynolda Rd Winston-Salem, Nc 27106 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: STATIN LACTONES IN STATIN TOXICITY Principal Investigator & Institution: Christians, Uwe; Associate Professor; Anesthesiology; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2003; Project Start 08-APR-2003; Project End 31-MAR-2007
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Summary: (provided by applicant): 3-Hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase inhibitors (statins) have emerged as the most valuable cholesterollowering drugs. Statins have wide therapeutic indeces and are generally well tolerated. However, the combination of statins with mainly triglyceride-lowering fibrates, especially nicotinic acid or gemfibrozil, or potent cytochrome P450/p-glycoprotein inhibitors significantly increases the risk to develop myopathy such as potentially fatal rhabdomyolysis. A recent example stressing the clinical importance of statin/fibrate drug interactions is the removal of cerivastatin from the market on August 8, 2001 after at least 40 fatal cases of rhabdomyolysis were reported when cerivastatin was coadministered with the fibrate gemfibrozil. Although for each statin an equilibrium between both acid and lactone form exists in vivo, very little attention has been paid to the potential role of the lactones of statins administered as open acids (atorvastatin, cerivastatin, fluvastatin, pravastatin) in pharmacokinetic and pharmacodynamic drug interactions and toxicity.This is surprising since the lactone forms are considerably more lipophilic than the acid forms, and it seems reasonable to assume that their access and affinities to cytochrome P450 enzymes, transporters and their tissue distribution, e.g. into muscle cells, differs significantly from the acids. It is our hypothesis that the statin lactones play a key role in statin pharmacokinetics and toxicity. To identify the role of statin lactones in statin toxicity, we will assess both lactone pharmacokinetics and their pharmacodynamic effects on liver and muscle cell metabolism using magnetic resonance spectroscopy (MRS). It will be our primary goal to assess the mechanistic role of statin lactones in the pharmacokinetics, toxicity and drug-drug interactions of statins in comparison to their corresponding acids. Our secondary goal will be to compare the lactones/acids of the different statins with each other. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TACROLIMUS VS INTENSIVE PREDNISONE IN PEDIATRIC FSGS Principal Investigator & Institution: Kaskel, Frederick J.; Developmental Renal and Electrolyte Phys; Montefiore Medical Center (Bronx, Ny) Bronx, Ny 104672490 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): Focal Segmental Glomerulosclerosis (FSGS) is a major cause of chronic kidney disease in childhood. This glomerulopaty is more frequent in minority populations, and often recurs in the transplanted kidney. Despite advances particulary in molecular genetics, the cause and optimal treatment of this condition remains poorly defined. Uncontrolled studies in adults with FSGS support the use of prolonged prednisone therapy. Preliminary data in children suggests that the calcineurin inhibitor tacrolimus may be efficacious in patients who have been refractory to other therapies. The purpose of this multicenter study is to compare the relative efficacy of tacrolimus with that of intensive prednisone therapy in preventing the progression of primary FSGS. This represents the first controlled evaluation of these two promising therapies in children with FSGS. We are proposing a randomized, open-label clinical trial in patients with nephrotic range proteinuria who fail to respond to 4 weeks of oral prednisone and who are found to have FSGS on renal biopsy. Patients will be assigned to receive daily prednisone (60 mg/m2) for 3 months followed by either alternate day prednisone (40 mg/m2) for the ensuing 15 months or tacrolimus plus lowdose alternate day (10 mg/m2) for 18 months. In addition, patients will receive optimal doses of losartan and atorvostatin to control proteinuria, hypertension, and hypelipidemia. The primary outcome indicators will be: complete or partial remission of proteinuria, preservation of glomerular filtration rate, and prevention of renal scarring. Secondary outcome indicators will include correlation of response with a novel
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histopathologic classification, assessed by a centrol core pathology group. The study design will incorporate collection and storage of potentially important biological samples at the direction of the Data Coordinating Center and the Steering Committee of the NIDDK. The Eastern Regional Group for the Study of Focal Segmental Glomerulosclerosis in Children will be comprised of 41 sites under the direction of the Regional Coordinating Center at Montefiore Medical Center of the Albert Einstein College of Medicine. This project is expected to: 1) improve the outcome of children with FSGS, and, 2) create a nationwide network of clinical investigators that will facilitate future basic and clinical research in the field of pediatric nephrology, in general, and FSGS, in particular. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “atorvastatin” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for atorvastatin in the PubMed Central database: •
Do hypertensive patients with average cholesterol levels benefit from atorvastatin therapy? by Hackam DG.; 2003 Jun 24; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=161615
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Pharmacokinetic Interactions between Nelfinavir and 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitors Atorvastatin and Simvastatin. by Hsyu PH, Schultz-Smith MD, Lillibridge JH, Lewis RH, Kerr BM.; 2001 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=90851
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 3 4
Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.
With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print. 6 PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.
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number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with atorvastatin, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “atorvastatin” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for atorvastatin (hyperlinks lead to article summaries): •
A 52-week, multicenter, randomized, parallel-group, double-blind, double-dummy study to assess the efficacy of atorvastatin and simvastatin in reaching low-density lipoprotein cholesterol and triglyceride targets: the treat-to-target (3T) study. Author(s): Olsson AG, Eriksson M, Johnson O, Kjellstrom T, Lanke J, Larsen ML, Pedersen T, Tikkanen MJ, Wiklund O; 3T Study Investigators. Source: Clinical Therapeutics. 2003 January; 25(1): 119-38. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12637115&dopt=Abstract
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A comparison of simvastatin and atorvastatin up to maximal recommended doses in a large multicenter randomized clinical trial. Author(s): Illingworth DR, Crouse JR 3rd, Hunninghake DB, Davidson MH, Escobar ID, Stalenhoef AF, Paragh G, Ma PT, Liu M, Melino MR, O'Grady L, Mercuri M, Mitchel YB; Simvastatin Atorvastatin HDL Study Group. Source: Current Medical Research and Opinion. 2001; 17(1): 43-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11464446&dopt=Abstract
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A controlled, prospective study of the effects of atorvastatin on proteinuria and progression of kidney disease. Author(s): Bianchi S, Bigazzi R, Caiazza A, Campese VM. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 2003 March; 41(3): 565-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12612979&dopt=Abstract
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A double-blind trial on the effects of atorvastatin on glycemic control in Japanese diabetic patients with hypercholesterolemia. Author(s): Tanaka A, Yamada N, Saito Y, Kawakami M, Ohashi Y, Akanuma Y. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 2001 October; 312(1-2): 41-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11580908&dopt=Abstract
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A placebo-controlled trial examining atorvastatin in dyslipidemic patients undergoing CAPD. Author(s): Harris KP, Wheeler DC, Chong CC; Atorvastatin in CAPD Study Investigators. Continuous ambulatory peritoneal dialysis. Source: Kidney International. 2002 April; 61(4): 1469-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11918754&dopt=Abstract
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A preliminary evaluation of neural network analysis for pharmacodynamic modeling of the dosing of the hydroxymethylglutaryl coenzyme A-reductase inhibitors simvastatin and atorvastatin. Author(s): Moon A, Smith T. Source: Clinical Therapeutics. 2002 April; 24(4): 653-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12017409&dopt=Abstract
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A randomized, double-blind, placebo-controlled, 8-week study to evaluate the efficacy and safety of once daily atorvastatin (10 mg) in patients with elevated LDLcholesterol. Author(s): Wang KY, Ting CT. Source: Japanese Heart Journal. 2001 November; 42(6): 725-38. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11933922&dopt=Abstract
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A study of the interaction potential of azithromycin and clarithromycin with atorvastatin in healthy volunteers. Author(s): Amsden GW, Kuye O, Wei GC. Source: Journal of Clinical Pharmacology. 2002 April; 42(4): 444-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11936570&dopt=Abstract
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Acute cholestatic hepatitis after reinitiating treatment with atorvastatin. Author(s): Ridruejo E, Mando OG. Source: Journal of Hepatology. 2002 July; 37(1): 165-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12076881&dopt=Abstract
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Acute pancreatitis possibly associated with combined salicylate and atorvastatin therapy. Author(s): Miltiadous G, Anthopoulou A, Elisaf M. Source: Jop [electronic Resource] : Journal of the Pancreas. 2003 January; 4(1): 20-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12555012&dopt=Abstract
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Acute rhabdomyolysis after atorvastatin and fusidic acid therapy. Author(s): Wenisch C, Krause R, Fladerer P, El Menjawi I, Pohanka E. Source: The American Journal of Medicine. 2000 July; 109(1): 78. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10991749&dopt=Abstract
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Aggressive lipid lowering does not improve endothelial function in type 2 diabetes: the Diabetes Atorvastatin Lipid Intervention (DALI) Study: a randomized, doubleblind, placebo-controlled trial. Author(s): van Venrooij FV, van de Ree MA, Bots ML, Stolk RP, Huisman MV, Banga JD; DALI Study Group. Source: Diabetes Care. 2002 July; 25(7): 1211-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12087021&dopt=Abstract
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Alopecia associated with atorvastatin. Author(s): Segal AS. Source: The American Journal of Medicine. 2002 August 1; 113(2): 171. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12133763&dopt=Abstract
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An economic analysis of the Atorvastatin Comparative Cholesterol Efficacy and Safety Study (ACCESS). Author(s): Smith DG, McBurney CR. Source: Pharmacoeconomics. 2003; 21 Suppl 1: 13-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12648031&dopt=Abstract
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Anti-inflammatory effect of atorvastatin (80 mg) in unstable angina pectoris and nonQ-wave acute myocardial infarction. Author(s): Correia LC, Sposito AC, Lima JC, Magalhaes LP, Passos LC, Rocha MS, D'Oliveira A, Esteves JP. Source: The American Journal of Cardiology. 2003 August 1; 92(3): 298-301. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12888137&dopt=Abstract
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Apolipoprotein E genotype affects plasma lipid response to atorvastatin in a gender specific manner. Author(s): Pedro-Botet J, Schaefer EJ, Bakker-Arkema RG, Black DM, Stein EM, Corella D, Ordovas JM. Source: Atherosclerosis. 2001 September; 158(1): 183-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11500190&dopt=Abstract
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ARBITER: Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol: a randomized trial comparing the effects of atorvastatin and pravastatin on carotid intima medial thickness. Author(s): Taylor AJ, Kent SM, Flaherty PJ, Coyle LC, Markwood TT, Vernalis MN. Source: Circulation. 2002 October 15; 106(16): 2055-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12379573&dopt=Abstract
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Are antiplatelet effects of clopidogrel inhibited by atorvastatin? A research question formulated but not yet adequately tested. Author(s): Serebruany VL, Steinhubl SR, Hennekens CH. Source: Circulation. 2003 April 1; 107(12): 1568-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12668486&dopt=Abstract
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ASCOT-LLA: questions about the benefits of atorvastatin. Author(s): Drummond GA. Source: Lancet. 2003 June 7; 361(9373): 1987-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12801765&dopt=Abstract
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ASCOT-LLA: questions about the benefits of atorvastatin. Author(s): Trewby P. Source: Lancet. 2003 June 7; 361(9373): 1987. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12801764&dopt=Abstract
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ASCOT-LLA: questions about the benefits of atorvastatin. Author(s): Killestein J. Source: Lancet. 2003 June 7; 361(9373): 1986; Author Reply 1986-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12801762&dopt=Abstract
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ASCOT-LLA: questions about the benefits of atorvastatin. Author(s): Ravnskov U. Source: Lancet. 2003 June 7; 361(9373): 1986; Author Reply 1986-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12801761&dopt=Abstract
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ASCOT-LLA: questions about the benefits of atorvastatin. Author(s): Devroey D, Ginst LV. Source: Lancet. 2003 June 7; 361(9373): 1985-6; Author Reply 1986-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12801760&dopt=Abstract
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Atorvastatin activates PPAR-gamma and attenuates the inflammatory response in human monocytes. Author(s): Grip O, Janciauskiene S, Lindgren S. Source: Inflammation Research : Official Journal of the European Histamine Research Society. [et Al.]. 2002 February; 51(2): 58-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11926313&dopt=Abstract
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Atorvastatin affects C-reactive protein levels in patients with coronary artery disease. Author(s): Karaca I, Ilkay E, Akbulut M, Yavuzkir M, Pekdemir M, Akbulut H, Arslan N. Source: Current Medical Research and Opinion. 2003; 19(3): 187-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12803732&dopt=Abstract
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Atorvastatin and clopidogrel. Author(s): Damkier P. Source: Circulation. 2003 September 30; 108(13): E96; Author Reply E96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14517157&dopt=Abstract
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Atorvastatin and micronized fenofibrate alone and in combination in type 2 diabetes with combined hyperlipidemia. Author(s): Athyros VG, Papageorgiou AA, Athyrou VV, Demitriadis DS, Kontopoulos AG. Source: Diabetes Care. 2002 July; 25(7): 1198-202. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12087019&dopt=Abstract
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Atorvastatin and simvastatin in patients on hemodialysis: effects on lipoproteins, Creactive protein and in vivo oxidized LDL. Author(s): van den Akker JM, Bredie SJ, Diepenveen SH, van Tits LJ, Stalenhoef AF, van Leusen R. Source: Journal of Nephrology. 2003 March-April; 16(2): 238-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12768071&dopt=Abstract
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Atorvastatin and the ability of clopidogrel to inhibit platelet aggregation. Author(s): Shechter M. Source: Circulation. 2003 June 10; 107(22): E210; Author Reply E210. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12796420&dopt=Abstract
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Atorvastatin and the dyslipidemia of early renal failure. Author(s): Ozsoy RC, Kastelein JJ, Arisz L, Koopman MG. Source: Atherosclerosis. 2003 January; 166(1): 187-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12482566&dopt=Abstract
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Atorvastatin and thrombogenicity of the carotid atherosclerotic plaque: the ATROCAP study. Author(s): Cortellaro M, Cofrancesco E, Arbustini E, Rossi F, Negri A, Tremoli E, Gabrielli L, Camera M. Source: Thrombosis and Haemostasis. 2002 July; 88(1): 41-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12152675&dopt=Abstract
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Atorvastatin attenuates remnant lipoprotein-induced monocyte adhesion to vascular endothelium under flow conditions. Author(s): Kawakami A, Tanaka A, Nakajima K, Shimokado K, Yoshida M. Source: Circulation Research. 2002 August 9; 91(3): 263-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12169653&dopt=Abstract
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Atorvastatin decreases vascular endothelial growth factor in patients with coronary artery disease. Author(s): Franz Alber H, Dulak J, Frick M, Dichtl W, Schwarzacher SP, Pachinger O, Weidinger F. Source: Journal of the American College of Cardiology. 2002 June 19; 39(12): 1951-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12084593&dopt=Abstract
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Atorvastatin dose-dependently decreases hepatic lipase activity in type 2 diabetes: effect of sex and the LIPC promoter variant. Author(s): Berk-Planken II, Hoogerbrugge N, Stolk RP, Bootsma AH, Jansen H; DALI Study Group. Source: Diabetes Care. 2003 February; 26(2): 427-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12547874&dopt=Abstract
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Atorvastatin enhances the plasma clearance of chylomicron-like emulsions in subjects with atherogenic dyslipidemia: relevance to the in vivo metabolism of triglyceride-rich lipoproteins. Author(s): Sposito AC, Santos RD, Amancio RF, Ramires JA, Chapman MJ, Maranhao RC. Source: Atherosclerosis. 2003 February; 166(2): 311-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12535744&dopt=Abstract
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Atorvastatin for acute coronary syndromes. Author(s): Schwartz GG, Olsson AG, Ezekowitz MD, Ganz P, Oliver MF, Waters D, Zeiher A, Chaitman BR. Source: Jama : the Journal of the American Medical Association. 2001 August 1; 286(5): 533-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11476650&dopt=Abstract
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Atorvastatin for acute coronary syndromes. Author(s): Wierzbicki AS, Mikhaildis DP, Reynolds TR. Source: Jama : the Journal of the American Medical Association. 2001 August 1; 286(5): 532-3; Author Reply 533-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11476649&dopt=Abstract
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Atorvastatin improves blood rheology in patients with familial hypercholesterolemia (FH) on long-term LDL apheresis treatment. Author(s): Banyai S, Banyai M, Falger J, Jansen M, Alt E, Derfler K, Koppensteiner R. Source: Atherosclerosis. 2001 December; 159(2): 513-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11730833&dopt=Abstract
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Atorvastatin improves endothelial function in renal-transplant recipients. Author(s): Asberg A, Hartmann A, Fjeldsa E, Holdaas H. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2001 September; 16(9): 1920-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11522880&dopt=Abstract
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Atorvastatin improves metabolic control and endothelial function in type 2 diabetic patients: a placebo-controlled study. Author(s): Dalla Nora E, Passaro A, Zamboni PF, Calzoni F, Fellin R, Solini A. Source: J Endocrinol Invest. 2003 January; 26(1): 73-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12602538&dopt=Abstract
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Atorvastatin improves postprandial lipoprotein metabolism in normolipidemlic subjects. Author(s): Parhofer KG, Barrett PH, Schwandt P. Source: The Journal of Clinical Endocrinology and Metabolism. 2000 November; 85(11): 4224-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11095458&dopt=Abstract
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Atorvastatin in low-density lipoprotein apheresis-treated patients with homozygous and heterozygous familial hypercholesterolemia. Author(s): Goldammer A, Wiltschnig S, Heinz G, Jansen M, Stulnig T, Horl WH, Derfler K. Source: Metabolism: Clinical and Experimental. 2002 August; 51(8): 976-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12145769&dopt=Abstract
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Atorvastatin increases HDL cholesterol in hypercholesterolemic patients. Evidence of a relationship with baseline HDL cholesterol. Author(s): Branchi A, Fiorenza AM, Torri A, Muzio F, Berra C, Colombo E, Dalla Valle E, Rovellini A, Sommariva D. Source: Nutr Metab Cardiovasc Dis. 2002 February; 12(1): 24-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12125226&dopt=Abstract
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Atorvastatin lowers C-reactive protein and improves endothelium-dependent vasodilation in type 2 diabetes mellitus. Author(s): Tan KC, Chow WS, Tam SC, Ai VH, Lam CH, Lam KS. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 February; 87(2): 563-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11836286&dopt=Abstract
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Atorvastatin lowers lipoprotein(a) but not apolipoprotein(a) fragment levels in hypercholesterolemic subjects at high cardiovascular risk. Author(s): Gonbert S, Malinsky S, Sposito AC, Laouenan H, Doucet C, Chapman MJ, Thillet J. Source: Atherosclerosis. 2002 October; 164(2): 305-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12204802&dopt=Abstract
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Atorvastatin markedly improves type III hyperlipoproteinemia in association with reduction of both exogenous and endogenous apolipoprotein B-containing lipoproteins. Author(s): Ishigami M, Yamashita S, Sakai N, Hirano K, Hiraoka H, Nakamura T, Matsuzawa Y. Source: Atherosclerosis. 2003 June; 168(2): 359-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12801620&dopt=Abstract
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Atorvastatin plus pravastatin for the treatment of heterozygous familial hypercholesterolaemia--a pilot study. Author(s): Athyros VG, Papageorgiou AA, Demitriadis DS, Kontopoulos AG. Source: Current Medical Research and Opinion. 2001; 17(4): 267-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11922400&dopt=Abstract
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Atorvastatin preferentially reduces LDL-associated platelet-activating factor acetylhydrolase activity in dyslipidemias of type IIA and type IIB. Author(s): Tsimihodimos V, Karabina SA, Tambaki AP, Bairaktari E, Goudevenos JA, Chapman MJ, Elisaf M, Tselepis AD. Source: Arteriosclerosis, Thrombosis, and Vascular Biology. 2002 February 1; 22(2): 30611. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11834533&dopt=Abstract
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Atorvastatin reduces expression of leukocyte adhesion molecules in patients with hypercholesterolemia. Author(s): Stulc T, Vrablik M, Kasalova Z, Ceska R, Marinov I. Source: Atherosclerosis. 2003 January; 166(1): 197-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12482568&dopt=Abstract
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Atorvastatin reduces plasma levels of factor VII activity and factor VII antigen in patients with hyperlipidemia. Author(s): Morishita E, Minami S, Ishino C, Kanno M, Uotani C, Asakura H, Matsuda T, Nakao S. Source: J Atheroscler Thromb. 2002; 9(1): 72-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12238641&dopt=Abstract
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Atorvastatin reduces postprandial accumulation and cholesteryl ester transfer protein-mediated remodeling of triglyceride-rich lipoprotein subspecies in type IIb hyperlipidemia. Author(s): Guerin M, Egger P, Le Goff W, Soudant C, Dupuis R, Chapman MJ. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 November; 87(11): 4991-5000. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12414863&dopt=Abstract
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Atorvastatin reduces the ability of clopidogrel to inhibit platelet aggregation: a new drug-drug interaction. Author(s): Lau WC, Waskell LA, Watkins PB, Neer CJ, Horowitz K, Hopp AS, Tait AR, Carville DG, Guyer KE, Bates ER. Source: Circulation. 2003 January 7; 107(1): 32-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12515739&dopt=Abstract
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Atorvastatin suppresses interferon-gamma -induced neopterin formation and tryptophan degradation in human peripheral blood mononuclear cells and in monocytic cell lines. Author(s): Neurauter G, Wirleitner B, Laich A, Schennach H, Weiss G, Fuchs D. Source: Clinical and Experimental Immunology. 2003 February; 131(2): 264-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12562386&dopt=Abstract
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Atorvastatin therapy in hypercholesterolemic patients suppresses cellular uptake of oxidized-LDL by differentiating monocytes. Author(s): Fuhrman B, Koren L, Volkova N, Keidar S, Hayek T, Aviram M. Source: Atherosclerosis. 2002 September; 164(1): 179-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12119208&dopt=Abstract
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Atorvastatin treatment beneficially alters the lipoprotein profile and increases lowdensity lipoprotein particle diameter in patients with combined dyslipidemia and impaired fasting glucose/type 2 diabetes. Author(s): Pontrelli L, Parris W, Adeli K, Cheung RC. Source: Metabolism: Clinical and Experimental. 2002 March; 51(3): 334-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11887170&dopt=Abstract
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Atorvastatin treatment for hyperlipidemia in pediatric renal transplant recipients. Author(s): Argent E, Kainer G, Aitken M, Rosenberg AR, Mackie FE. Source: Pediatric Transplantation. 2003 February; 7(1): 38-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12581326&dopt=Abstract
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Atorvastatin versus four statin-fibrate combinations in patients with familial combined hyperlipidaemia. Author(s): Athyros VG, Papageorgiou AA, Athyrou VV, Demitriadis DS, Pehlivanidis AN, Kontopoulos AG. Source: Journal of Cardiovascular Risk. 2002 February; 9(1): 33-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11984215&dopt=Abstract
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Atorvastatin versus micronized fenofibrate in the treatment of patients with mixed hyperlipoproteinemia. Author(s): Milionis HJ, Bairaktari ET, Liberopoulos EN, Elisaf MS. Source: The American Journal of Cardiology. 2001 July 15; 88(2): 203. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11463061&dopt=Abstract
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Atorvastatin, diabetic dyslipidemia, and cognitive functioning. Author(s): Berk-Planken I, de Konig I, Stolk R, Jansen H, Hoogerbrugge N. Source: Diabetes Care. 2002 July; 25(7): 1250-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12087035&dopt=Abstract
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Atorvastatin. Author(s): Wierzbicki AS. Source: Expert Opinion on Pharmacotherapy. 2001 May; 2(5): 819-30. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11336625&dopt=Abstract
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Atorvastatin: an updated review of its pharmacological properties and use in dyslipidaemia. Author(s): Malhotra HS, Goa KL. Source: Drugs. 2001; 61(12): 1835-81. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11693468&dopt=Abstract
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Atorvastatin: in the management of hyperlipidaemia. Author(s): Curr Cardiol Rep. 2002 Nov;4(6):485 Source: Journal of Postgraduate Medicine. 2000 July-September; 46(3): 242-3. Review. /entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12379168
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Atorvastatin-clopidogrel interaction. Author(s): Martin PT, Denman R. Source: Circulation. 2003 June 24; 107(24): E223; Author Reply E223. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12821599&dopt=Abstract
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Atorvastatin-induced dermatomyositis. Author(s): Noel B, Cerottini JP, Panizzon RG. Source: The American Journal of Medicine. 2001 June 1; 110(8): 670-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11388341&dopt=Abstract
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Atorvastatin-induced diaphragmatic muscle impairment. Author(s): Sulem P, Bagheri H, Faixo Y, Montastruc JL. Source: The Annals of Pharmacotherapy. 2001 October; 35(10): 1292-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11675865&dopt=Abstract
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Atorvastatin-induced reversible positive antinuclear antibodies. Author(s): Jimenez-Alonso J, Jaimez L, Sabio JM, Hidalgo C, Leon L. Source: The American Journal of Medicine. 2002 March; 112(4): 329-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11893380&dopt=Abstract
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Attaining United Kingdom-European Atherosclerosis Society low-density lipoprotein cholesterol guideline target values in the Greek Atorvastatin and Coronary-heartdisease Evaluation (GREACE) Study. Author(s): Athyros VG, Mikhailidis DP, Papageorgiou AA, Mercouris BR, Athyrou VV, Symeonidis AN, Basayannis EO, Demitriadis DS, Kontopoulos AG. Source: Current Medical Research and Opinion. 2002; 18(8): 499-502. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12564661&dopt=Abstract
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Autoimmune hepatitis revealed by atorvastatin. Author(s): Pelli N, Setti M, Ceppa P, Toncini C, Indiveri F. Source: European Journal of Gastroenterology & Hepatology. 2003 August; 15(8): 921-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12867804&dopt=Abstract
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Avasimibe and atorvastatin synergistically reduce cholesteryl ester content in THP-1 macrophages. Author(s): Llaverias G, Jove M, Vazquez-Carrera M, Sanchez RM, Diaz C, Hernandez G, Laguna JC, Alegret M. Source: European Journal of Pharmacology. 2002 September 6; 451(1): 11-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12223223&dopt=Abstract
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Beneficial effects of atorvastatin in the treatment of hyperlipidemia after renal transplantation. Author(s): Demetriou D, Shabpar A, Bohmig G, Schmaldienst S, Horl WH, Watschinger B. Source: Wiener Klinische Wochenschrift. 2000 April 21; 112(8): 358-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10849941&dopt=Abstract
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Benefits of atorvastatin in cholesterol lowering. Author(s): Farmer JA. Source: Current Atherosclerosis Reports. 2003 March; 5(2): 94-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12573192&dopt=Abstract
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Bilateral pharmacokinetic interaction between cyclosporine A and atorvastatin in renal transplant recipients. Author(s): Asberg A, Hartmann A, Fjeldsa E, Bergan S, Holdaas H. Source: American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2001 November; 1(4): 382-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12099384&dopt=Abstract
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Both fenofibrate and atorvastatin improve vascular reactivity in combined hyperlipidaemia (fenofibrate versus atorvastatin trial--FAT). Author(s): Malik J, Melenovsky V, Wichterle D, Haas T, Simek J, Ceska R, Hradec J. Source: Cardiovascular Research. 2001 November; 52(2): 290-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11684077&dopt=Abstract
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By the way, doctor. I'm 84, 5-foot-9, and weigh 160. I do an hour's exercise every day. I take a diuretic, potassium, and calcium-channel blocker. Should I also take Lipitor to avoid a heart attack? Author(s): Lee TH. Source: Harvard Health Letter / from Harvard Medical School. 2003 April; 28(6): 8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12777236&dopt=Abstract
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By the way, doctor. My hair has been thinning out for the past decade or so, but since my doctor started me on Lipitor (atorvastatin) a few months ago for high cholesterol, I swear it's been falling out much faster. My doctor discounts the possibility, but I looked in the Physicians' desk reference (PDR) and alopecia is listed under “adverse reactions.” What do you think? Author(s): Lee TH. Source: Harvard Health Letter / from Harvard Medical School. 2000 July; 25(9): 8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10877883&dopt=Abstract
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Can early treatment with atorvastatin (Lipitor) improve the outcome of patients with acute coronary syndromes? Author(s): Johnson K, Breen WJ. Source: The Journal of Family Practice. 2001 July; 50(7): 572. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11485701&dopt=Abstract
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Cerivastatin and atorvastatin inhibit IL-3-dependent differentiation and IgEmediated histamine release in human basophils and downmodulate expression of the basophil-activation antigen CD203c/E-NPP3. Author(s): Majlesi Y, Samorapoompichit P, Hauswirth AW, Schernthaner GH, Ghannadan M, Baghestanian M, Rezaie-Majd A, Valenta R, Sperr WR, Buhring HJ, Valent P. Source: Journal of Leukocyte Biology. 2003 January; 73(1): 107-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12525568&dopt=Abstract
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Changes in coronary plaque color and morphology by lipid-lowering therapy with atorvastatin: serial evaluation by coronary angioscopy. Author(s): Takano M, Mizuno K, Yokoyama S, Seimiya K, Ishibashi F, Okamatsu K, Uemura R. Source: Journal of the American College of Cardiology. 2003 August 20; 42(4): 680-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12932601&dopt=Abstract
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Chitotriosidase genotype and serum activity in subjects with combined hyperlipidemia: effect of the lipid-lowering agents, atorvastatin and bezafibrate. Author(s): Canudas J, Cenarro A, Civeira F, Garci-Otin AL, Aristegui R, Diaz C, Masramon X, Sol JM, Hernandez G, Pocovi M. Source: Metabolism: Clinical and Experimental. 2001 April; 50(4): 447-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11288040&dopt=Abstract
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Cholesterol reduction with atorvastatin improves walking distance in patients with peripheral arterial disease. Author(s): Mohler ER 3rd, Hiatt WR, Creager MA. Source: Circulation. 2003 September 23; 108(12): 1481-6. Epub 2003 Sep 02. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12952839&dopt=Abstract
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Chronic urticaria to atorvastatin. Author(s): Anliker MD, Wuthrich B. Source: Allergy. 2002 April; 57(4): 366. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11906371&dopt=Abstract
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Cimetidine does not alter atorvastatin pharmacokinetics or LDL-cholesterol reduction. Author(s): Stern RH, Gibson DM, Whitfield LR. Source: European Journal of Clinical Pharmacology. 1998 February; 53(6): 475-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9551707&dopt=Abstract
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Coadministration of colesevelam hydrochloride with atorvastatin lowers LDL cholesterol additively. Author(s): Hunninghake D, Insull W Jr, Toth P, Davidson D, Donovan JM, Burke SK. Source: Atherosclerosis. 2001 October; 158(2): 407-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11583720&dopt=Abstract
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Combined treatment with fibrates and small doses of atorvastatin in patients with mixed hyperlipidemia. Author(s): Liamis G, Kakafika A, Bairaktari E, Miltiadous G, Tsimihodimos V, Goudevenos J, Achimastos A, Elisaf M. Source: Current Medical Research and Opinion. 2002; 18(3): 125-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12094821&dopt=Abstract
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Common cholesteryl ester transfer protein gene polymorphisms and the effect of atorvastatin therapy in type 2 diabetes. Author(s): van Venrooij FV, Stolk RP, Banga JD, Sijmonsma TP, van Tol A, Erkelens DW, Dallinga-Thie GM; DALI Study Group. Source: Diabetes Care. 2003 April; 26(4): 1216-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12663600&dopt=Abstract
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Comparative dose efficacy study of atorvastatin versus simvastatin, pravastatin, lovastatin, and fluvastatin in patients with hypercholesterolemia (the CURVES study) Author(s): Pincus J. Source: The American Journal of Cardiology. 1998 August 1; 82(3): 406-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9708683&dopt=Abstract
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Comparative dose efficacy study of atorvastatin versus simvastatin, pravastatin, lovastatin, and fluvastatin in patients with hypercholesterolemia (the CURVES study) Author(s): Jones P, Kafonek S, Laurora I, Hunninghake D. Source: The American Journal of Cardiology. 1998 March 1; 81(5): 582-7. Erratum In: Am J Cardiol 1998 July 1; 82(1): 128. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9514454&dopt=Abstract
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Comparative effects of atorvastatin, simvastatin, and fenofibrate on serum homocysteine levels in patients with primary hyperlipidemia. Author(s): Milionis HJ, Papakostas J, Kakafika A, Chasiotis G, Seferiadis K, Elisaf MS. Source: Journal of Clinical Pharmacology. 2003 August; 43(8): 825-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12953339&dopt=Abstract
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Comparative effects of rosuvastatin and atorvastatin across their dose ranges in patients with hypercholesterolemia and without active arterial disease. Author(s): Schneck DW, Knopp RH, Ballantyne CM, McPherson R, Chitra RR, Simonson SG. Source: The American Journal of Cardiology. 2003 January 1; 91(1): 33-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12505568&dopt=Abstract
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Comparative effects of simvastatin and atorvastatin in hypercholesterolemic patients with characteristics of metabolic syndrome. Author(s): Hunninghake DB, Ballantyne CM, Maccubbin DL, Shah AK, Gumbiner B, Mitchel YB. Source: Clinical Therapeutics. 2003 June; 25(6): 1670-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12860491&dopt=Abstract
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Comparative efficacy study of atorvastatin vs simvastatin, pravastatin, lovastatin and placebo in type 2 diabetic patients with hypercholesterolaemia. Author(s): Gentile S, Turco S, Guarino G, Sasso CF, Amodio M, Magliano P, Salvatore T, Corigliano G, Agrusta M, De Simone G, Gaeta I, Oliviero B, Torella R. Source: Diabetes, Obesity & Metabolism. 2000 December; 2(6): 355-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11225965&dopt=Abstract
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Comparing the efficacy and safety of atorvastatin and simvastatin in Asians with elevated low-density lipoprotein-cholesterol--a multinational, multicenter, doubleblind study. Author(s): Wu CC, Sy R, Tanphaichitr V, Hin AT, Suyono S, Lee YT. Source: J Formos Med Assoc. 2002 July; 101(7): 478-87. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12353340&dopt=Abstract
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Comparison of atorvastatin alone versus simvastatin +/- cholestyramine in the management of severe primary hypercholesterolaemia (the six cities study). Author(s): Simons LA. Source: Aust N Z J Med. 1998 June; 28(3): 327-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9673745&dopt=Abstract
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Comparison of clinical benefits of clopidogrel therapy in patients with acute coronary syndromes taking atorvastatin versus other statin therapies. Author(s): Wienbergen H, Gitt AK, Schiele R, Juenger C, Heer T, Meisenzahl C, Limbourg P, Bossaller C, Senges J; MITRA PLUS Study Group. Source: The American Journal of Cardiology. 2003 August 1; 92(3): 285-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12888133&dopt=Abstract
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Comparison of effect of intensive lipid lowering with atorvastatin to less intensive lowering with lovastatin on C-reactive protein in patients with stable angina pectoris and inducible myocardial ischemia. Author(s): Kinlay S, Timms T, Clark M, Karam C, Bilodeau T, Ridker PM, Rifai N, Carlson W, Lloyd-Jones DM, Johnstone M, Rubenstein J, Alexander S, Orav J, Stone PH; Vascular Basis Study Group. Source: The American Journal of Cardiology. 2002 May 15; 89(10): 1205-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12008177&dopt=Abstract
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Comparison of effects of simvastatin versus atorvastatin on high-density lipoprotein cholesterol and apolipoprotein A-I levels. Author(s): Kastelein JJ, Isaacsohn JL, Ose L, Hunninghake DB, Frohlich J, Davidson MH, Habib R, Dujovne CA, Crouse JR, Liu M, Melino MR, O'Grady L, Mercuri M, Mitchel YB. Source: The American Journal of Cardiology. 2000 July 15; 86(2): 221-3. Erratum In: Am J Cardiol 2000 October 1; 86(7): 812. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10913488&dopt=Abstract
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Comparison of effects on low-density lipoprotein cholesterol and high-density lipoprotein cholesterol with rosuvastatin versus atorvastatin in patients with type IIa or IIb hypercholesterolemia. Author(s): Davidson M, Ma P, Stein EA, Gotto AM Jr, Raza A, Chitra R, Hutchinson H. Source: The American Journal of Cardiology. 2002 February 1; 89(3): 268-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11809427&dopt=Abstract
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Comparison of efficacy and safety of atorvastatin (10mg) with simvastatin (10mg) at six weeks. ASSET Investigators. Author(s): Insull W, Kafonek S, Goldner D, Zieve F. Source: The American Journal of Cardiology. 2001 March 1; 87(5): 554-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11230838&dopt=Abstract
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Comparison of efficacy and safety of atorvastatin and simvastatin in patients with dyslipidemia with and without coronary heart disease. Author(s): Karalis DG, Ross AM, Vacari RM, Zarren H, Scott R. Source: The American Journal of Cardiology. 2002 March 15; 89(6): 667-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11897207&dopt=Abstract
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Comparison of extended-release niacin and atorvastatin monotherapies and combination treatment of the atherogenic lipid profile in diabetes mellitus. Author(s): Van JT, Pan J, Wasty T, Chan E, Wu X, Charles MA. Source: The American Journal of Cardiology. 2002 June 1; 89(11): 1306-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12031735&dopt=Abstract
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Comparison of one-year efficacy and safety of atorvastatin versus lovastatin in primary hypercholesterolemia. Atorvastatin Study Group I. Author(s): Davidson M, McKenney J, Stein E, Schrott H, Bakker-Arkema R, Fayyad R, Black D. Source: The American Journal of Cardiology. 1997 June 1; 79(11): 1475-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9185636&dopt=Abstract
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Comparison of the effects of atorvastatin or fenofibrate on nonlipid biochemical risk factors and the LDL particle size in subjects with combined hyperlipidemia. Author(s): Melenovsky V, Malik J, Wichterle D, Simek J, Pisarikova A, Skrha J, Poledne R, Stavek P, Ceska R. Source: American Heart Journal. 2002 October; 144(4): E6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12360175&dopt=Abstract
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Comparison of the effects of atorvastatin versus simvastatin on subclinical atherosclerosis in primary preventionas determined by electronbeam tomography. Author(s): Hecht HS, Harman SM. Source: The American Journal of Cardiology. 2003 January 1; 91(1): 42-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12505569&dopt=Abstract
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Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (STELLAR* Trial). Author(s): Jones PH, Davidson MH, Stein EA, Bays HE, McKenney JM, Miller E, Cain VA, Blasetto JW; STELLAR Study Group. Source: The American Journal of Cardiology. 2003 July 15; 92(2): 152-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12860216&dopt=Abstract
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Comparison of the efficacy and tolerability of policosanol with atorvastatin in elderly patients with type II hypercholesterolaemia. Author(s): Castano G, Mas R, Fernandez L, Illnait J, Mesa M, Alvarez E, Lezcay M. Source: Drugs & Aging. 2003; 20(2): 153-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12534315&dopt=Abstract
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Comparison of the efficacy and tolerability of simvastatin and atorvastatin in the treatment of hypercholesterolemia. Author(s): Recto CS 2nd, Acosta S, Dobs A. Source: Clin Cardiol. 2000 September; 23(9): 682-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11016019&dopt=Abstract
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Comparison of the efficacy of atorvastatin and micronized fenofibrate in the treatment of mixed hyperlipidemia. Author(s): Bairaktari ET, Tzallas CS, Tsimihodimos VK, Liberopoulos EN, Miltiadous GA, Elisaf MS. Source: Journal of Cardiovascular Risk. 1999 April; 6(2): 113-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10353071&dopt=Abstract
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Comparison of the efficacy of atorvastatin versus cerivastatin in primary hypercholesterolemia. Author(s): Hunninghake D, Insull W, Knopp R, Davidson M, Lohrbauer L, Jones P, Kafonek S. Source: The American Journal of Cardiology. 2001 September 15; 88(6): 635-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11564386&dopt=Abstract
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Comparison of the frequency of adverse events in patients treated with atorvastatin or simvastatin. Author(s): Abourjaily HM, Alsheikh-Ali AA, Karas RH. Source: The American Journal of Cardiology. 2003 April 15; 91(8): 999-1002, A7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12686348&dopt=Abstract
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Comparison of therapy with simvastatin 80 mg and atorvastatin 80 mg in patients with familial hypercholesterolaemia. Author(s): Wierzbicki AS, Lumb PJ, Chik G, Crook MA. Source: Int J Clin Pract. 1999 December; 53(8): 609-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10692755&dopt=Abstract
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Cost-effectiveness of sevelamer versus calcium carbonate plus atorvastatin to reduce LDL in patients with chronic renal insufficiency with dyslipidemia and hyperphosphatemia. Author(s): Brophy DF, Wallace JF, Kennedy DT, Gehr TW, Holdford DA. Source: Pharmacotherapy. 2000 August; 20(8): 950-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10939556&dopt=Abstract
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Cost-minimization analysis of simvastatin versus atorvastatin for maintenance therapy in patients with coronary or peripheral vascular disease. Author(s): Attanasio E, Russo P, Allen SE. Source: Clinical Therapeutics. 2001 February; 23(2): 276-83; Discussion 274-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11293560&dopt=Abstract
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Decreased production of low density lipoprotein by atorvastatin after apheresis in homozygous familial hypercholesterolemia. Author(s): Marais AD, Naoumova RP, Firth JC, Penny C, Neuwirth CK, Thompson GR. Source: Journal of Lipid Research. 1997 October; 38(10): 2071-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9374129&dopt=Abstract
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Dermographism: an adverse effect of atorvastatin. Author(s): Adcock BB, Hornsby LB, Jenkins K. Source: The Journal of the American Board of Family Practice / American Board of Family Practice. 2001 March-April; 14(2): 148-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11314923&dopt=Abstract
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Design and rationale of the ARBITER trial (Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol)--a randomized trial comparing the effects of atorvastatin and pravastatin on carotid artery intima-media thickness. Author(s): Markwood TT, Kent SM, Coyle LC, Flaherty PJ, O'Malley PG, Taylor AJ. Source: American Heart Journal. 2001 March; 141(3): 342-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11231429&dopt=Abstract
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Design of the Collaborative AtoRvastatin Diabetes Study (CARDS) in patients with type 2 diabetes. Author(s): Colhoun HM, Thomason MJ, Mackness MI, Maton SM, Betteridge DJ, Durrington PN, Hitman GA, Neil HA, Fuller JH; Collaborative AtoRvastatin Diabetes Study (CARDS). Source: Diabetic Medicine : a Journal of the British Diabetic Association. 2002 March; 19(3): 201-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11918622&dopt=Abstract
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Design of the Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE IT)-TIMI 22 trial. Author(s): Cannon CP, McCabe CH, Belder R, Breen J, Braunwald E. Source: The American Journal of Cardiology. 2002 April 1; 89(7): 860-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11909576&dopt=Abstract
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Development and validation of a high-performance liquid chromatography tandem mass spectrometry assay for atorvastatin, ortho-hydroxy atorvastatin, and parahydroxy atorvastatin in human, dog, and rat plasma. Author(s): Bullen WW, Miller RA, Hayes RN. Source: Journal of the American Society for Mass Spectrometry. 1999 January; 10(1): 5566. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9888185&dopt=Abstract
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Development, validation, and interlaboratory comparison of an HMG-CoA reductase inhibition assay for quantitation of atorvastatin in plasma matrices. Author(s): Shum YY, Huang N, Walter G, Black A, Sekerke C, Chang T, Whitfield LR. Source: Therapeutic Drug Monitoring. 1998 February; 20(1): 41-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9485553&dopt=Abstract
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Differential regulation of lipoprotein kinetics by atorvastatin and fenofibrate in subjects with the metabolic syndrome. Author(s): Watts GF, Barrett PH, Ji J, Serone AP, Chan DC, Croft KD, Loehrer F, Johnson AG. Source: Diabetes. 2003 March; 52(3): 803-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12606523&dopt=Abstract
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Do hypertensive patients with average cholesterol levels benefit from atorvastatin therapy? Author(s): Hackam DG. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 2003 June 24; 168(13): 1689. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12821623&dopt=Abstract
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Dose-dependent action of atorvastatin in type IIB hyperlipidemia: preferential and progressive reduction of atherogenic apoB-containing lipoprotein subclasses (VLDL2, IDL, small dense LDL) and stimulation of cellular cholesterol efflux. Author(s): Guerin M, Egger P, Soudant C, Le Goff W, van Tol A, Dupuis R, Chapman MJ. Source: Atherosclerosis. 2002 August; 163(2): 287-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12052475&dopt=Abstract
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Dose-response effects of atorvastatin and simvastatin on high-density lipoprotein cholesterol in hypercholesterolaemic patients: a review of five comparative studies. Author(s): Wierzbicki AS, Mikhailidis DP. Source: International Journal of Cardiology. 2002 July; 84(1): 53-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12104065&dopt=Abstract
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Dosing of atorvastatin and increases in fibrinogen level. Author(s): Sinzinger H, Rodrigues M, Furberg CD. Source: Atherosclerosis. 1999 December; 147(2): 421-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10627270&dopt=Abstract
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Drug-induced rhabdomyolysis after concomitant use of clarithromycin, atorvastatin, and lopinavir/ritonavir in a patient with HIV. Author(s): Mah Ming JB, Gill MJ. Source: Aids Patient Care and Stds. 2003 May; 17(5): 207-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12816614&dopt=Abstract
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Effect of atorvastatin (80 mg) and simvastatin (40 mg) on plasma fibrinogen levels and on carotid intima media thickness in patients with familial hypercholesterolemia. Author(s): Trip MD, van Wissen S, Smilde TJ, Hutten BA, Stalenhoef AF, Kastelein JJ. Source: The American Journal of Cardiology. 2003 March 1; 91(5): 604-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12615272&dopt=Abstract
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Effect of atorvastatin (80 mg) initiated at the time of coronary artery stent implantation on C-reactive protein and six-month clinical events. Author(s): Gaspardone A, Versaci F, Proietti I, Tomai F, Altamura L, Skossyreva O, Chiariello L. Source: The American Journal of Cardiology. 2002 October 1; 90(7): 786-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12356402&dopt=Abstract
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Effect of atorvastatin (80 mg) on recurrent ischemia in unstable angina pectoris or non-ST-elevation acute myocardial infarction. Author(s): Correia LC, Magalhaes LP, Santana O, Rocha MS, Passos LC, D'Oliveira A Jr, Esteves JP, Sposito AC. Source: The American Journal of Cardiology. 2003 June 1; 91(11): 1355-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12767434&dopt=Abstract
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Effect of atorvastatin 15 mg/week on serum lipids in patients with hypercholesterolemia. Author(s): Rindone JP, Dzurick J, Hiller D, Peralta B. Source: The American Journal of Cardiology. 2001 February 1; 87(3): 341-2, A9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11165974&dopt=Abstract
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Effect of atorvastatin and bezafibrate on plasma levels of C-reactive protein in combined (mixed) hyperlipidemia. Author(s): Gomez-Gerique JA, Ros E, Olivan J, Mostaza JM, Vilardell M, Pinto X, Civeira F, Hernandez A, da Silva PM, Rodriguez-Botaro A, Zambon D, Lima J, Diaz C, Aristegui R, Sol JM, Chaves J, Hernandez G; ATOMIX Investigators. Source: Atherosclerosis. 2002 June; 162(2): 245-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11996943&dopt=Abstract
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Effect of atorvastatin and clopidogrel on cellular immune function. Author(s): Kroger K, Lindemann M, Kreuzfelder E, Brocker M, Santosa F, Grosse-Wilde H. Source: Prostaglandins, Leukotrienes, and Essential Fatty Acids. 2003 March; 68(3): 2515. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12591010&dopt=Abstract
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Effect of atorvastatin and fenofibrate on autonomic tone in subjects with combined hyperlipidemia. Author(s): Melenovsky V, Wichterle D, Simek J, Malik J, Haas T, Ceska R, Malik M. Source: The American Journal of Cardiology. 2003 August 1; 92(3): 337-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12888150&dopt=Abstract
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Effect of atorvastatin and fish oil on plasma high-sensitivity C-reactive protein concentrations in individuals with visceral obesity. Author(s): Chan DC, Watts GF, Barrett PH, Beilin LJ, Mori TA. Source: Clinical Chemistry. 2002 June; 48(6 Pt 1): 877-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12029003&dopt=Abstract
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Effect of atorvastatin and fluvastatin on the expression of plasminogen activator inhibitor type-1 in cultured human endothelial cells. Author(s): Lopez S, Peiretti F, Bonardo B, Juhan-Vague I, Nalbone G. Source: Atherosclerosis. 2000 October; 152(2): 359-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10998463&dopt=Abstract
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Effect of atorvastatin and pravastatin on serum C-reactive protein. Author(s): Kent SM, Flaherty PJ, Coyle LC, Markwood TT, Taylor AJ. Source: American Heart Journal. 2003 February; 145(2): E8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12595863&dopt=Abstract
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Effect of atorvastatin on adhesive phenotype of human endothelial cells activated by tumor necrosis factor alpha. Author(s): Bernot D, Benoliel AM, Peiretti F, Lopez S, Bonardo B, Bongrand P, JuhanVague I, Nalbone G. Source: Journal of Cardiovascular Pharmacology. 2003 February; 41(2): 316-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12548094&dopt=Abstract
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Effect of atorvastatin on apolipoprotein B100 containing lipoprotein metabolism in type-2 diabetes. Author(s): Ouguerram K, Magot T, Zair Y, Marchini JS, Charbonnel B, Laouenan H, Krempf M. Source: The Journal of Pharmacology and Experimental Therapeutics. 2003 July; 306(1): 332-7. Epub 2003 April 08. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12684543&dopt=Abstract
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Effect of atorvastatin on apolipoprotein B48 metabolism and low-density lipoprotein receptor activity in normolipidemic patients with coronary artery disease. Author(s): Dane-Stewart CA, Watts GF, Pal S, Chan D, Thompson P, Hung J, Mamo JC. Source: Metabolism: Clinical and Experimental. 2003 October; 52(10): 1279-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14564679&dopt=Abstract
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Effect of atorvastatin on chylomicron remnant metabolism in visceral obesity: a study employing a new stable isotope breath test. Author(s): Chan DC, Watts GF, Barrett PH, Martins IJ, James AP, Mamo JC, Mori TA, Redgrave TG. Source: Journal of Lipid Research. 2002 May; 43(5): 706-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11971941&dopt=Abstract
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Effect of atorvastatin on endothelium-dependent vasodilation in patients with coronary artery disease. Author(s): Vita JA, Gokce N, Duffy SJ, Kahn D, Tomasian D, Palmisano J, Thomas S, Holbrook M, Keaney JF Jr. Source: The American Journal of Cardiology. 2003 April 1; 91(7): 857-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12667571&dopt=Abstract
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Effect of atorvastatin on endothelium-dependent vasodilation in postmenopausal women with average serum cholesterol levels. Author(s): Mercuro G, Zoncu S, Saiu F, Sarais C, Rosano GM. Source: The American Journal of Cardiology. 2002 October 1; 90(7): 747-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12356389&dopt=Abstract
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Effect of atorvastatin on hemorheologic-hemostatic parameters and serum fibrinogen levels in hyperlipidemic patients. Author(s): Dujovne CA, Harris WS, Altman R, Overhiser RW, Black DM. Source: The American Journal of Cardiology. 2000 February 1; 85(3): 350-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11078305&dopt=Abstract
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Effect of atorvastatin on LDL oxidation and antioxidants in normocholesterolemic type 2 diabetic patients. Author(s): Oranje WA, Sels JP, Rondas-Colbers GJ, Lemmens PJ, Wolffenbuttel BH. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 2001 September 25; 311(2): 91-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11566168&dopt=Abstract
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Effect of atorvastatin on low-density lipoprotein subtypes in patients with different forms of hyperlipoproteinemia and control subjects. Author(s): Geiss HC, Otto C, Schwandt P, Parhofer KG. Source: Metabolism: Clinical and Experimental. 2001 August; 50(8): 983-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11474489&dopt=Abstract
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Effect of atorvastatin on myocardial contractile reserve assessed by tissue Doppler imaging in moderately hypercholesterolemic patients without heart disease. Author(s): Bountioukos M, Rizzello V, Krenning BJ, Bax JJ, Kertai MD, Vourvouri EC, Schinkel AF, Biagini E, Boersma E, Roelandt JR, Poldermans D. Source: The American Journal of Cardiology. 2003 September 1; 92(5): 613-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12943890&dopt=Abstract
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Effect of atorvastatin on plasma apoE metabolism in patients with combined hyperlipidemia. Author(s): Cohn JS, Tremblay M, Batal R, Jacques H, Veilleux L, Rodriguez C, Barrett PH, Dubreuil D, Roy M, Bernier L, Mamer O, Davignon J. Source: Journal of Lipid Research. 2002 September; 43(9): 1464-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12235178&dopt=Abstract
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Effect of atorvastatin on plasminogen activator inhibitor type-1 synthesis in human monocytes/macrophages. Author(s): Lopez S, Peiretti F, Bonardo B, Deprez-Beauclair P, Laouenan H, JuhanVague I, Nalbone G. Source: Journal of Cardiovascular Pharmacology. 2001 June; 37(6): 762-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11392473&dopt=Abstract
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Effect of atorvastatin on postcardiac transplant increase in low-density lipoprotein cholesterol reduces development of intimal hyperplasia and progression of endothelial dysfunction. Author(s): See VY Jr, DeNofrio D, Goldberg L, Chang G, Sasseen B, Kolansky DM, Pickering F, Kao A, Loh E, Wilensky RL. Source: The American Journal of Cardiology. 2003 July 1; 92(1): 11-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12842237&dopt=Abstract
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Effect of atorvastatin on serum creatinine levels. Author(s): Kakafika A, Liamis G, Elisaf M, Mikhailidis D. Source: Current Medical Research and Opinion. 2001; 17(3): 230-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11900317&dopt=Abstract
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Effect of atorvastatin on serum uric acid levels. Author(s): Kakafika A, Tsimihodimos V, Elisaf M. Source: Atherosclerosis. 2001 September; 158(1): 255. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11550660&dopt=Abstract
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Effect of atorvastatin on total lipid profiles assessed by analytical capillary isotachophoresis. Author(s): Zhang B, Noda K, Saku K. Source: Cardiology. 2003; 99(4): 211-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12845248&dopt=Abstract
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Effect of atorvastatin treatment on lipoprotein lipase mass in the pre-heparin plasma in Japanese hyperlipidemic subjects. Author(s): Kobayashi J, Maruyama T, Masuda M, Shinomiya M. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 2001 December; 314(1-2): 261-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11718706&dopt=Abstract
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Effect of atorvastatin, simvastatin, and lovastatin on the metabolism of cholesterol and triacylglycerides in HepG2 cells. Author(s): Scharnagl H, Schinker R, Gierens H, Nauck M, Wieland H, Marz W. Source: Biochemical Pharmacology. 2001 December 1; 62(11): 1545-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11728391&dopt=Abstract
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Effect of ezetimibe coadministered with atorvastatin in 628 patients with primary hypercholesterolemia: a prospective, randomized, double-blind trial. Author(s): Ballantyne CM, Houri J, Notarbartolo A, Melani L, Lipka LJ, Suresh R, Sun S, LeBeaut AP, Sager PT, Veltri EP; Ezetimibe Study Group. Source: Circulation. 2003 May 20; 107(19): 2409-15. Epub 2003 April 28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12719279&dopt=Abstract
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Effect of food on the pharmacodynamics and pharmacokinetics of atorvastatin, an inhibitor of HMG-CoA reductase. Author(s): Whitfield LR, Stern RH, Sedman AJ, Abel R, Gibson DM. Source: Eur J Drug Metab Pharmacokinet. 2000 April-June; 25(2): 97-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11112089&dopt=Abstract
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Effect of niacin and atorvastatin on lipoprotein subclasses in patients with atherogenic dyslipidemia. Author(s): McKenney JM, McCormick LS, Schaefer EJ, Black DM, Watkins ML. Source: The American Journal of Cardiology. 2001 August 1; 88(3): 270-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11472706&dopt=Abstract
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Effectiveness of low doses of simvastatin versus atorvastatin: resolving conflicting evidence. Author(s): Chong C, Kelly S, Bradley M. Source: Clinical Therapeutics. 2002 February; 24(2): 325-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11911562&dopt=Abstract
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Effects of amlodipine, atorvastatin and combination of both on advanced atherosclerotic plaque in APOE*3-Leiden transgenic mice. Author(s): van de Poll SW, Delsing DJ, Wouter Jukema J, Princen HM, Havekes LM, Puppels GJ, van der Laarse A. Source: Journal of Molecular and Cellular Cardiology. 2003 January; 35(1): 109-18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12623305&dopt=Abstract
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Effects of atorvastatin (and blood pressure lowering comparing amlodipide-based therapy with beta-blocker-based therapy) on serum variables of cholesterol synthesis and absorption, thrombogenicity and on low-density lipoprotein oxidation in vivo. Author(s): Nieminen MS, Viikari J, Ahotupa M, Vasankari T, Kantola I, Strandberg T, Vanhanen H; Anglo-Scandinavian Cardiac Outcomes Trial. Source: Journal of Human Hypertension. 2001 August; 15 Suppl 1: S27-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11685905&dopt=Abstract
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Effects of atorvastatin 80 mg daily early after onset of unstable angina pectoris or non-Q-wave myocardial infarction. Author(s): Colivicchi F, Guido V, Tubaro M, Ammirati F, Montefoschi N, Varveri A, Santini M. Source: The American Journal of Cardiology. 2002 October 15; 90(8): 872-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12372577&dopt=Abstract
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Effects of atorvastatin and vitamin C on endothelial function of hypercholesterolemic patients. Author(s): Perticone F, Ceravolo R, Maio R, Cloro C, Candigliota M, Scozzafava A, Mongiardo A, Mastroroberto P, Chello M, Mattioli PL. Source: Atherosclerosis. 2000 October; 152(2): 511-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10998481&dopt=Abstract
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Effects of atorvastatin on aortic pulse wave velocity in patients with hypertension and hypercholesterolaemia: a preliminary study. Author(s): Raison J, Rudnichi A, Safar ME. Source: Journal of Human Hypertension. 2002 October; 16(10): 705-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12420194&dopt=Abstract
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Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial. Author(s): Schwartz GG, Olsson AG, Ezekowitz MD, Ganz P, Oliver MF, Waters D, Zeiher A, Chaitman BR, Leslie S, Stern T; Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) Study Investigators. Source: Jama : the Journal of the American Medical Association. 2001 April 4; 285(13): 1711-8. Summary for Patients In: http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11277825&dopt=Abstract
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Effects of atorvastatin on electrophoretic characteristics of LDL particles among subjects with heterozygous familial hypercholesterolemia. Author(s): Lariviere M, Lamarche B, Pirro M, Hogue JC, Bergeron J, Gagne C, Couture P. Source: Atherosclerosis. 2003 March; 167(1): 97-104. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12618273&dopt=Abstract
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Effects of atorvastatin on fasting and postprandial lipoprotein subclasses in coronary heart disease patients versus control subjects. Author(s): Schaefer EJ, McNamara JR, Tayler T, Daly JA, Gleason JA, Seman LJ, Ferrari A, Rubenstein JJ. Source: The American Journal of Cardiology. 2002 October 1; 90(7): 689-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12356379&dopt=Abstract
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Effects of atorvastatin on oxidized low-density lipoprotein, low-density lipoprotein subfraction distribution, and remnant lipoprotein in patients with mixed hyperlipoproteinemia. Author(s): Sasaki S, Kuwahara N, Kunitomo K, Harada S, Yamada T, Azuma A, Takeda K, Nakagawa M. Source: The American Journal of Cardiology. 2002 February 15; 89(4): 386-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11835916&dopt=Abstract
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Effects of atorvastatin on postprandial plasma lipoproteins in postinfarction patients with combined hyperlipidaemia. Author(s): Boquist S, Karpe F, Danell-Toverud K, Hamsten A. Source: Atherosclerosis. 2002 May; 162(1): 163-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11947910&dopt=Abstract
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Effects of atorvastatin on renal function in patients with chronic renal failure. Author(s): Cianciaruso B, Torraca S, Somma G, Pisani A, Sabbatini M. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2002 October; 17(10): 1858-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12271007&dopt=Abstract
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Effects of atorvastatin on stroke in patients with unstable angina or non-Q-wave myocardial infarction: a Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) substudy. Author(s): Waters DD, Schwartz GG, Olsson AG, Zeiher A, Oliver MF, Ganz P, Ezekowitz M, Chaitman BR, Leslie SJ, Stern T; MIRACL Study Investigators. Source: Circulation. 2002 September 24; 106(13): 1690-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12270864&dopt=Abstract
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Effects of atorvastatin on the HDL subpopulation profile of coronary heart disease patients. Author(s): Asztalos BF, Horvath KV, McNamara JR, Roheim PS, Rubinstein JJ, Schaefer EJ. Source: Journal of Lipid Research. 2002 October; 43(10): 1701-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12364554&dopt=Abstract
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Effects of atorvastatin treatment on sICAM-1 and plasma nitric oxide levels in hypercholesterolemic subjects. Author(s): Sardo MA, Castaldo M, Cinquegrani M, Bonaiuto M, Maesano A, Versace A, Spadaro M, Campo S, Nicocia G, Altavilla D, Saitta A. Source: Clinical and Applied Thrombosis/Hemostasis : Official Journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis. 2002 July; 8(3): 257-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12361204&dopt=Abstract
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Effects of atorvastatin versus fenofibrate on lipoprotein profiles, low-density lipoprotein subfraction distribution, and hemorheologic parameters in type 2 diabetes mellitus with mixed hyperlipoproteinemia. Author(s): Frost RJ, Otto C, Geiss HC, Schwandt P, Parhofer KG. Source: The American Journal of Cardiology. 2001 January 1; 87(1): 44-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11137832&dopt=Abstract
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Effects of low doses of simvastatin and atorvastatin on high-density lipoprotein cholesterol levels in patients with hypercholesterolemia. Author(s): Branchi A, Fiorenza AM, Torri A, Muzio F, Berra C, Colombo E, Dalla Valle E, Rovellini A, Sommariva D. Source: Clinical Therapeutics. 2001 June; 23(6): 851-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11440285&dopt=Abstract
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Effects of micronized fenofibrate versus atorvastatin in the treatment of dyslipidaemic patients with low plasma HDL-cholesterol levels: a 12-week randomized trial. Author(s): Despres JP, Lemieux I, Salomon H, Delaval D. Source: Journal of Internal Medicine. 2002 June; 251(6): 490-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12028504&dopt=Abstract
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Effects of rosiglitazone alone and in combination with atorvastatin on the metabolic abnormalities in type 2 diabetes mellitus. Author(s): Freed MI, Ratner R, Marcovina SM, Kreider MM, Biswas N, Cohen BR, Brunzell JD; Rosiglitazone Study 108 investigators. Source: The American Journal of Cardiology. 2002 November 1; 90(9): 947-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12398960&dopt=Abstract
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Effects of rosuvastatin and atorvastatin compared over 52 weeks of treatment in patients with hypercholesterolemia. Author(s): Olsson AG, Istad H, Luurila O, Ose L, Stender S, Tuomilehto J, Wiklund O, Southworth H, Pears J, Wilpshaar JW; Rosuvastatin Investigators Group. Source: American Heart Journal. 2002 December; 144(6): 1044-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12486429&dopt=Abstract
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Effects of short-term atorvastatin treatment on global fibrinolytic capacity, and sLselectin and sFas levels in hyperlipidemic patients with coronary artery disease. Author(s): Atalar E, Ozmen F, Haznedaroglu I, Acil T, Ozer N, Ovunc K, Aksoyek S, Kes S. Source: International Journal of Cardiology. 2002 August; 84(2-3): 227-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12127376&dopt=Abstract
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Effects of simvastatin and atorvastatin on inflammation markers in plasma. Author(s): Wiklund O, Mattsson-Hulten L, Hurt-Camejo E, Oscarsson J. Source: Journal of Internal Medicine. 2002 April; 251(4): 338-47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11952885&dopt=Abstract
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Efficacy and drug interactions of the new HMG-CoA reductase inhibitors cerivastatin and atorvastatin in CsA-treated renal transplant recipients. Author(s): Renders L, Mayer-Kadner I, Koch C, Scharffe S, Burkhardt K, Veelken R, Schmieder RE, Hauser IA. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2001 January; 16(1): 141-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11209008&dopt=Abstract
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Efficacy and safety of atorvastatin 10 mg every other day in hypercholesterolemia. Author(s): Piamsomboon C, Laothavorn P, Saguanwong S, Chatlaong B, Nasawadi C, Tanprasert P, Pongsiri K. Source: J Med Assoc Thai. 2002 March; 85(3): 297-300. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12117017&dopt=Abstract
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Efficacy and safety of atorvastatin after pediatric heart transplantation. Author(s): Chin C, Gamberg P, Miller J, Luikart H, Bernstein D. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2002 November; 21(11): 1213-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12431495&dopt=Abstract
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Efficacy and safety of atorvastatin in children and adolescents with familial hypercholesterolemia or severe hyperlipidemia: a multicenter, randomized, placebocontrolled trial. Author(s): McCrindle BW, Ose L, Marais AD. Source: The Journal of Pediatrics. 2003 July; 143(1): 74-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12915827&dopt=Abstract
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Efficacy and safety of atorvastatin in hyperlipidemic, type 2 diabetic patients. A 34week, multicenter, open-label study. Author(s): Aguilar-Salinas CA, Gomez-Perez FJ, Posadas-Romero C, Vazquez-Chavez C, Meaney E, Gulias-Herrero A, Guillen LE, Alvarado Vega A, Mendoza Perez E, Eduardo Romero-Nava L, Angelica Gomez-Diaz R, Salinas-Orozco S, Moguel R, Novoa G. Source: Atherosclerosis. 2000 October; 152(2): 489-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10998478&dopt=Abstract
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Efficacy and safety of atorvastatin in the treatment of hypercholesterolemia associated with antiretroviral therapy. Author(s): Palacios R, Santos J, Gonzalez M, Ruiz J, Valdivielso P, Marquez M, Gonzalez-Santos P. Source: Journal of Acquired Immune Deficiency Syndromes (1999). 2002 August 15; 30(5): 536-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12154347&dopt=Abstract
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Efficacy and safety of ezetimibe coadministered with atorvastatin or simvastatin in patients with homozygous familial hypercholesterolemia. Author(s): Gagne C, Gaudet D, Bruckert E; Ezetimibe Study Group. Source: Circulation. 2002 May 28; 105(21): 2469-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12034651&dopt=Abstract
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Efficacy of alternate-day dosing versus daily dosing of atorvastatin. Author(s): Jafari M, Ebrahimi R, Ahmadi-Kashani M, Balian H, Bashir M. Source: Journal of Cardiovascular Pharmacology and Therapeutics. 2003 June; 8(2): 1236. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12808485&dopt=Abstract
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Efficacy of atorvastatin and gemfibrozil, alone and in low dose combination, in the treatment of diabetic dyslipidemia. Author(s): Wagner AM, Jorba O, Bonet R, Ordonez-Llanos J, Perez A. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 July; 88(7): 3212-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12843167&dopt=Abstract
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Efficacy of atorvastatin in achieving National Cholesterol Education Program lowdensity lipoprotein targets in women with severe dyslipidemia and cardiovascular disease or risk factors for cardiovascular disease: The Women's Atorvastatin Trial on Cholesterol (WATCH). Author(s): McPherson R, Angus C, Murray P, Genest J Jr; WATCH Investigators. Source: American Heart Journal. 2001 June; 141(6): 949-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11376309&dopt=Abstract
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Efficacy of atorvastatin in treating high risk patients to reach low density lipoproteincholesterol goals: the Treat to Target (TTT-Israel) Study. Author(s): Leibovitz E, Harats D, Gavish D. Source: Isr Med Assoc J. 2002 June; 4(6): 407-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12073409&dopt=Abstract
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Efficacy of combination of atorvastatin and micronised fenofibrate in the treatment of severe mixed hyperlipidemia. Author(s): Kiortisis DN, Millionis H, Bairaktari E, Elisaf MS. Source: European Journal of Clinical Pharmacology. 2000 December; 56(9-10): 631-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11214768&dopt=Abstract
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Factorial study of the effects of atorvastatin and fish oil on dyslipidaemia in visceral obesity. Author(s): Chan DC, Watts GF, Mori TA, Barrett PH, Beilin LJ, Redgrave TG. Source: European Journal of Clinical Investigation. 2002 June; 32(6): 429-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12059988&dopt=Abstract
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Fibrinogen response with simvastatin versus atorvastatin in familial hypercholesterolemia. Author(s): Wierzbicki AS, Lumb PJ, Chik G, Crook MA. Source: The American Journal of Cardiology. 2001 February 1; 87(3): 338-40, A9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11165973&dopt=Abstract
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Grapefruit juice increases serum concentrations of atorvastatin and has no effect on pravastatin. Author(s): Lilja JJ, Kivisto KT, Neuvonen PJ. Source: Clinical Pharmacology and Therapeutics. 1999 August; 66(2): 118-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10460065&dopt=Abstract
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Guidelines for lowering lipids to reduce coronary artery disease risk: a comparison of rosuvastatin with atorvastatin, pravastatin, and simvastatin for achieving lipidlowering goals. Author(s): Shepherd J, Hunninghake DB, Barter P, McKenney JM, Hutchinson HG. Source: The American Journal of Cardiology. 2003 March 6; 91(5A): 11C-17C; Discussion 17C-19C. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12646338&dopt=Abstract
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HDL-cholesterol and the treatment of coronary heart disease: contrasting effects of atorvastatin and simvastatin. Author(s): Mikhailidis DP, Wierzbicki AS. Source: Current Medical Research and Opinion. 2000; 16(2): 139-46. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10893658&dopt=Abstract
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Heart rate variability after long-term treatment with atorvastatin in hypercholesterolaemic patients with or without coronary artery disease. Author(s): Pehlivanidis AN, Athyros VG, Demitriadis DS, Papageorgiou AA, Bouloukos VJ, Kontopoulos AG. Source: Atherosclerosis. 2001 August; 157(2): 463-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11472748&dopt=Abstract
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Hemostatic effects of atorvastatin versus simvastatin. Author(s): Kadikoylu G, Yukselen V, Yavasoglu I, Bolaman Z. Source: The Annals of Pharmacotherapy. 2003 April; 37(4): 478-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12659599&dopt=Abstract
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Hepatic responses to inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase: a comparison of atorvastatin and simvastatin. Author(s): Bergstrom JD, Bostedor RG, Rew DJ, Geissler WM, Wright SD, Chao YS. Source: Biochimica Et Biophysica Acta. 1998 January 23; 1389(3): 213-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9512650&dopt=Abstract
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High doses of atorvastatin do not affect activity of prothrombinase in patients with acute coronary syndromes. Author(s): Olivotti L, Ghigliotti G, Spallarossa P, Leslie S, Rossettin P, Barsotti A, Brunelli C. Source: Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis. 2002 June; 13(4): 315-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12032397&dopt=Abstract
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High-density lipoprotein cholesterol and triglyceride response with simvastatin versus atorvastatin in familial hypercholesterolemia. Author(s): Wierzbicki AS, Lumb PJ, Chik G, Crook MA. Source: The American Journal of Cardiology. 2000 September 1; 86(5): 547-9, A9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11009276&dopt=Abstract
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High-dose atorvastatin enhances the decline in inflammatory markers in patients with acute coronary syndromes in the MIRACL study. Author(s): Kinlay S, Schwartz GG, Olsson AG, Rifai N, Leslie SJ, Sasiela WJ, Szarek M, Libby P, Ganz P; Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering Study Investigators. Source: Circulation. 2003 September 30; 108(13): 1560-6. Epub 2003 Sep 15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12975259&dopt=Abstract
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High-dose atorvastatin therapy in severe heterozygous familial hypercholesterolaemia. Author(s): Wierzbicki AS, Lumb PJ, Semra YK, Crook MA. Source: Qjm : Monthly Journal of the Association of Physicians. 1998 April; 91(4): 291-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9666952&dopt=Abstract
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Homocysteine and lipid lowering agents. A comparison between atorvastatin and fenofibrate in patients with mixed hyperlipidemia. Author(s): Giral P, Bruckert E, Jacob N, Chapman MJ, Foglietti MJ, Turpin G. Source: Atherosclerosis. 2001 February 1; 154(2): 421-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11166775&dopt=Abstract
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Implications of the atorvastatin versus revascularization treatment (AVERT) study for the clinician. Author(s): Eisenberg D. Source: Current Cardiology Reports. 2000 September; 2(5): 433-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10980911&dopt=Abstract
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Influence of atorvastatin and simvastatin on apolipoprotein B metabolism in moderate combined hyperlipidemic subjects with low VLDL and LDL fractional clearance rates. Author(s): Forster LF, Stewart G, Bedford D, Stewart JP, Rogers E, Shepherd J, Packard CJ, Caslake MJ. Source: Atherosclerosis. 2002 September; 164(1): 129-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12119202&dopt=Abstract
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Influence of atorvastatin versus simvastatin on fibrinogen and other hemorheological parameters in patients with severe hypercholesterolemia treated with regular lowdensity lipoprotein immunoadsorption apheresis. Author(s): Otto C, Geiss HC, Donner MG, Parhofer KG, Schwandt P. Source: Therapeutic Apheresis : Official Journal of the International Society for Apheresis and the Japanese Society for Apheresis. 2000 June; 4(3): 244-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10910028&dopt=Abstract
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Inhibition of cholesterol synthesis by atorvastatin in homozygous familial hypercholesterolaemia. Author(s): Raal FJ, Pappu AS, Illingworth DR, Pilcher GJ, Marais AD, Firth JC, Kotze MJ, Heinonen TM, Black DM. Source: Atherosclerosis. 2000 June; 150(2): 421-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10856535&dopt=Abstract
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Is a mechanical or a metabolic approach superior in the treatment of coronary disease? Results of the atorvastatin versus revascularization (AVERT) trial. Author(s): Mikhaildis DP, Wierzbicki AS, Reynolds TM. Source: European Heart Journal. 2001 June; 22(11): 972-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11428822&dopt=Abstract
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Is a mechanical or a metabolic approach superior in the treatment of coronary disease? Results of the atorvastatin versus revascularization (AVERT) trial. Author(s): Waters D. Source: European Heart Journal. 2000 July; 21(13): 1029-31. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10843815&dopt=Abstract
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Is alternate daily dose of atorvastatin effective in treating patients with hyperlipidemia? The Alternate Day Versus Daily Dosing of Atorvastatin Study (ADDAS). Author(s): Matalka MS, Ravnan MC, Deedwania PC. Source: American Heart Journal. 2002 October; 144(4): 674-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12360164&dopt=Abstract
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Itraconazole alters the pharmacokinetics of atorvastatin to a greater extent than either cerivastatin or pravastatin. Author(s): Mazzu AL, Lasseter KC, Shamblen EC, Agarwal V, Lettieri J, Sundaresen P. Source: Clinical Pharmacology and Therapeutics. 2000 October; 68(4): 391-400. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11061579&dopt=Abstract
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Lack of adverse clopidogrel-atorvastatin clinical interaction from secondary analysis of a randomized, placebo-controlled clopidogrel trial. Author(s): Saw J, Steinhubl SR, Berger PB, Kereiakes DJ, Serebruany VL, Brennan D, Topol EJ; Clopidogrel for the Reduction of Events During Observation Investigators. Source: Circulation. 2003 August 26; 108(8): 921-4. Epub 2003 Aug 18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12925453&dopt=Abstract
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Lactonization is the critical first step in the disposition of the 3-hydroxy-3methylglutaryl-CoA reductase inhibitor atorvastatin. Author(s): Jacobsen W, Kuhn B, Soldner A, Kirchner G, Sewing KF, Kollman PA, Benet LZ, Christians U. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 2000 November; 28(11): 1369-78. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11038166&dopt=Abstract
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Linear IgA bullous dermatosis induced by atorvastatin. Author(s): Konig C, Eickert A, Scharfetter-Kochanek K, Krieg T, Hunzelmann N. Source: Journal of the American Academy of Dermatology. 2001 April; 44(4): 689-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11260550&dopt=Abstract
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Lipid and apolipoprotein levels and distribution in patients with hypertriglyceridemia: effect of triglyceride reductions with atorvastatin. Author(s): Le NA, Innis-Whitehouse W, Li X, Bakker-Arkema R, Black D, Brown WV. Source: Metabolism: Clinical and Experimental. 2000 February; 49(2): 167-77. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10690940&dopt=Abstract
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Lipid and apolipoprotein ratios: association with coronary artery disease and effects of rosuvastatin compared with atorvastatin, pravastatin, and simvastatin. Author(s): Rader DJ, Davidson MH, Caplan RJ, Pears JS. Source: The American Journal of Cardiology. 2003 March 6; 91(5A): 20C-23C; Discussion 23C-24C. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12646340&dopt=Abstract
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Lipid-lowering effect of atorvastatin in heart transplantation. Author(s): Almenar Bonet L, Martinez-Dolz L, Arnau Vives MA, Rueda Soriano J, Osa Saez A, Dicenta Gisbert F, Palencia Perez M. Source: Transplantation Proceedings. 2002 February; 34(1): 179-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11959239&dopt=Abstract
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Lipitor (atorvastatin calcium) tablets. Author(s): Claussen DW. Source: Gastroenterology Nursing : the Official Journal of the Society of Gastroenterology Nurses and Associates. 1998 September-October; 21(5): 219-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9830966&dopt=Abstract
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Long term efficacy and safety of atorvastatin in the treatment of severe type III and combined dyslipidaemia. Author(s): van Dam M, Zwart M, de Beer F, Smelt AH, Prins MH, Trip MD, Havekes LM, Lansberg PJ, Kastelein JJ. Source: Heart (British Cardiac Society). 2002 September; 88(3): 234-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12181212&dopt=Abstract
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Long-term (18-month) efficacy of atorvastatin therapy in type 2 diabetics at cardiovascular risk. Author(s): Velussi M. Source: Nutr Metab Cardiovasc Dis. 2002 February; 12(1): 29-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12125227&dopt=Abstract
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Long-term treatment effect of atorvastatin on aortic stiffness in hypercholesterolaemic patients. Author(s): Kontopoulos AG, Athyros VG, Pehlivanidis AN, Demitriadis DS, Papageorgiou AA, Boudoulas H. Source: Current Medical Research and Opinion. 2003; 19(1): 22-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12661776&dopt=Abstract
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Long-term treatment with atorvastatin in adolescent males with heterozygous familial hypercholesterolemia. Author(s): Athyros VG, Papageorgiou AA, Kontopoulos AG. Source: Atherosclerosis. 2002 July; 163(1): 205-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12048142&dopt=Abstract
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Low-dose atorvastatin therapy does not augment endothelial function in active hypercholesterolaemic males. Author(s): Parnell MM, Chin-Dusting JP, Starr J, Kaye DM. Source: British Journal of Clinical Pharmacology. 2003 February; 55(2): 212-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12580994&dopt=Abstract
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Medical therapy versus revascularization: the atorvastatin versus revascularization treatment AVERT trial. Author(s): Waters DD. Source: The Canadian Journal of Cardiology. 2000 January; 16 Suppl A: 11A-3A. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10653925&dopt=Abstract
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More on atorvastatin and fibrinogen. Author(s): Otto C, Schwandt P. Source: Atherosclerosis. 2000 August; 151(2): 591-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10944081&dopt=Abstract
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More on the effect of atorvastatin on plasma fibrinogen levels in primary hypercholesterolaemia. Author(s): Wierzbicki AS, Crook MA, Nair DR, Mikhailidis DP, Winder AF. Source: Atherosclerosis. 2000 January; 148(1): 204. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10644290&dopt=Abstract
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More on the effect of atorvastatin on plasma fibrinogen levels in primary hypercholesterolemia. Author(s): Bertolotto A, Bandinelli S, Ruocco L, Lo Faro A, Penno G, Navalesi R. Source: Atherosclerosis. 1999 April; 143(2): 455-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10217377&dopt=Abstract
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Multiorgan failure induced by atorvastatin. Author(s): Sreenarasimhaiah J, Shiels P, Lisker-Melman M. Source: The American Journal of Medicine. 2002 September; 113(4): 348-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12361829&dopt=Abstract
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Multiple-dose pharmacokinetics, pharmacodynamics, and safety of atorvastatin, an inhibitor of HMG-CoA reductase, in healthy subjects. Author(s): Cilla DD Jr, Whitfield LR, Gibson DM, Sedman AJ, Posvar EL. Source: Clinical Pharmacology and Therapeutics. 1996 December; 60(6): 687-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8988072&dopt=Abstract
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No difference in plasma fibrinogen levels between CAPD patients taking atorvastatin and simvastatin. Author(s): Singhal MK, Bhaskaran S, Szabo T, La Rosa R. Source: Perit Dial Int. 1999 January-February; 19(1): 89-91. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10201354&dopt=Abstract
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Not acute but chronic hypertriglyceridemia is associated with impaired endotheliumdependent vasodilation: reversal after lipid-lowering therapy by atorvastatin. Author(s): de Man FH, Weverling-Rijnsburger AW, van der Laarse A, Smelt AH, Jukema JW, Blauw GJ. Source: Arteriosclerosis, Thrombosis, and Vascular Biology. 2000 March; 20(3): 744-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10712400&dopt=Abstract
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Pharmacodynamic effects and pharmacokinetics of atorvastatin after administration to normocholesterolemic subjects in the morning and evening. Author(s): Cilla DD Jr, Gibson DM, Whitfield LR, Sedman AJ. Source: Journal of Clinical Pharmacology. 1996 July; 36(7): 604-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8844442&dopt=Abstract
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Pharmacodynamics and pharmacokinetic-pharmacodynamic relationships of atorvastatin, an HMG-CoA reductase inhibitor. Author(s): Stern RH, Yang BB, Hounslow NJ, MacMahon M, Abel RB, Olson SC. Source: Journal of Clinical Pharmacology. 2000 June; 40(6): 616-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10868312&dopt=Abstract
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Pharmacokinetic interactions between nelfinavir and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors atorvastatin and simvastatin. Author(s): Hsyu PH, Schultz-Smith MD, Lillibridge JH, Lewis RH, Kerr BM. Source: Antimicrobial Agents and Chemotherapy. 2001 December; 45(12): 3445-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11709322&dopt=Abstract
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Possible short-term amelioration of basilar plaque by high-dose atorvastatin: use of reductase inhibitors for intracranial plaque stabilization. Author(s): Callahan AS 3rd, Berger BL, Beuter MJ, Devlin TG. Source: Journal of Neuroimaging : Official Journal of the American Society of Neuroimaging. 2001 April; 11(2): 202-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11296593&dopt=Abstract
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Potential interaction between troglitazone and atorvastatin. Author(s): DiTusa L, Luzier AB. Source: Journal of Clinical Pharmacy and Therapeutics. 2000 August; 25(4): 279-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10971778&dopt=Abstract
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Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the AngloScandinavian Cardiac Outcomes Trial--Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Author(s): Sever PS, Dahlof B, Poulter NR, Wedel H, Beevers G, Caulfield M, Collins R, Kjeldsen SE, Kristinsson A, McInnes GT, Mehlsen J, Nieminen M, O'Brien E, Ostergren J; ASCOT investigators. Source: Lancet. 2003 April 5; 361(9364): 1149-58. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12686036&dopt=Abstract
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Prolonged inhibition of cholesterol synthesis by atorvastatin inhibits apo B-100 and triglyceride secretion from HepG2 cells. Author(s): Funatsu T, Suzuki K, Goto M, Arai Y, Kakuta H, Tanaka H, Yasuda S, Ida M, Nishijima S, Miyata K. Source: Atherosclerosis. 2001 July; 157(1): 107-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11427209&dopt=Abstract
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Prolonged inhibition of cholesterol synthesis explains the efficacy of atorvastatin. Author(s): Naoumova RP, Dunn S, Rallidis L, Abu-Muhana O, Neuwirth C, Rendell NB, Taylor GW, Thompson GR. Source: Journal of Lipid Research. 1997 July; 38(7): 1496-500. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9254075&dopt=Abstract
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Quantitation of the acid and lactone forms of atorvastatin and its biotransformation products in human serum by high-performance liquid chromatography with electrospray tandem mass spectrometry. Author(s): Jemal M, Ouyang Z, Chen BC, Teitz D. Source: Rapid Communications in Mass Spectrometry : Rcm. 1999; 13(11): 1003-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10368976&dopt=Abstract
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Rapid effects on vascular function after initiation and withdrawal of atorvastatin in healthy, normocholesterolemic men. Author(s): Laufs U, Wassmann S, Hilgers S, Ribaudo N, Bohm M, Nickenig G. Source: The American Journal of Cardiology. 2001 December 1; 88(11): 1306-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11728362&dopt=Abstract
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Rate of low-density lipoprotein cholesterol and apolipoprotein B changes on initiation and discontinuation of atorvastatin treatment. Author(s): Stern RH, Abel RB. Source: Journal of Clinical Pharmacology. 1997 April; 37(4): 291-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9115054&dopt=Abstract
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Rationale and design of the Myocardial Ischemia Reduction With Aggressive Cholesterol lowering (MIRACL) Study that evaluates atorvastatin in unstable angina pectoris and in non-Q-wave acute myocardial infarction. Author(s): Ghali JK. Source: The American Journal of Cardiology. 1998 September 1; 82(5): 703. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9732912&dopt=Abstract
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Rationale and design of the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) study that evaluates atorvastatin in unstable angina pectoris and in non-Q-wave acute myocardial infarction. Author(s): Schwartz GG, Oliver MF, Ezekowitz MD, Ganz P, Waters D, Kane JP, Texter M, Pressler ML, Black D, Chaitman BR, Olsson AG. Source: The American Journal of Cardiology. 1998 March 1; 81(5): 578-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9514453&dopt=Abstract
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Rationale and design of the St. Francis Heart Study: a randomized clinical trial of atorvastatin plus antioxidants in asymptomatic persons with elevated coronary calcification. Author(s): Arad Y, Newstein D, Roth M, Guerci AD. Source: Controlled Clinical Trials. 2001 October; 22(5): 553-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11578788&dopt=Abstract
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Rationale, design, and baseline characteristics of a trial comparing aggressive lipid lowering with Atorvastatin Versus Revascularization Treatments (AVERT). Author(s): McCormick LS, Black DM, Waters D, Brown WV, Pitt B. Source: The American Journal of Cardiology. 1997 November 1; 80(9): 1130-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9359537&dopt=Abstract
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Re: Gomez-Gerique, et al. Effect of atorvastatin and bezafibrate on plasma levels of C-reactive protein in combined (mixed) hyperlipidemia. Atherosclerosis 2002;162:24551. Author(s): Moriarty PM, Backes JM. Source: Atherosclerosis. 2003 January; 166(1): 201. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12564455&dopt=Abstract
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Reduced expression of endothelial cell markers after 1 year treatment with simvastatin and atorvastatin in patients with coronary heart disease. Author(s): Seljeflot I, Tonstad S, Hjermann I, Arnesen H. Source: Atherosclerosis. 2002 May; 162(1): 179-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11947912&dopt=Abstract
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Reduction of LDL cholesterol by 25% to 60% in patients with primary hypercholesterolemia by atorvastatin, a new HMG-CoA reductase inhibitor. Author(s): Nawrocki JW, Weiss SR, Davidson MH, Sprecher DL, Schwartz SL, Lupien PJ, Jones PH, Haber HE, Black DM. Source: Arteriosclerosis, Thrombosis, and Vascular Biology. 1995 May; 15(5): 678-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7749881&dopt=Abstract
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Related factors of meeting National Cholesterol Education Program-recommended goals with atorvastatin. Author(s): Yoshitomi Y, Tsujibayashi T, Ishii T, Sakurai S, Nagakura C, Miyauchi A; National Cholesterol Education Program. Source: J Atheroscler Thromb. 2003; 10(1): 19-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12621160&dopt=Abstract
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Renal dysfunction does not alter the pharmacokinetics or LDL-cholesterol reduction of atorvastatin. Author(s): Stern RH, Yang BB, Horton M, Moore S, Abel RB, Olson SC. Source: Journal of Clinical Pharmacology. 1997 September; 37(9): 816-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9549635&dopt=Abstract
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Reversible atorvastatin-associated external ophthalmoplegia, anti-acetylcholine receptor antibodies, and ataxia. Author(s): Negevesky GJ, Kolsky MP, Laureno R, Yau TH. Source: Archives of Ophthalmology. 2000 March; 118(3): 427-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10721974&dopt=Abstract
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Rhabdomyolysis after taking atorvastatin with gemfibrozil. Author(s): Duell PB, Connor WE, Illingworth DR. Source: The American Journal of Cardiology. 1998 February 1; 81(3): 368-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9468088&dopt=Abstract
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Rhabdomyolysis associated with concomitant use of atorvastatin and cyclosporine. Author(s): Maltz HC, Balog DL, Cheigh JS. Source: The Annals of Pharmacotherapy. 1999 November; 33(11): 1176-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10573315&dopt=Abstract
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Rhabdomyolysis causing AV blockade due to possible atorvastatin, esomeprazole, and clarithromycin interaction. Author(s): Sipe BE, Jones RJ, Bokhart GH. Source: The Annals of Pharmacotherapy. 2003 June; 37(6): 808-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12773066&dopt=Abstract
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Rhabdomyolysis with acute renal failure probably related to the interaction of atorvastatin and delavirdine. Author(s): Castro JG, Gutierrez L. Source: The American Journal of Medicine. 2002 April 15; 112(6): 505. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11959068&dopt=Abstract
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Rhabdomyolysis with concurrent atorvastatin and diltiazem. Author(s): Lewin JJ 3rd, Nappi JM, Taylor MH. Source: The Annals of Pharmacotherapy. 2002 October; 36(10): 1546-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12243603&dopt=Abstract
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Risk of adverse events with concomitant use of atorvastatin or simvastatin and glucose-lowering drugs (thiazolidinediones, metformin, sulfonylurea, insulin, and acarbose). Author(s): Alsheikh-Ali AA, Abourjaily HM, Karas RH. Source: The American Journal of Cardiology. 2002 June 1; 89(11): 1308-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12031736&dopt=Abstract
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Role of statins in the management of dyslipidemia after cardiac transplant: randomized controlled trial comparing the efficacy and the safety of atorvastatin with pravastatin. Author(s): Magnani G, Carinci V, Magelli C, Potena L, Reggiani LB, Branzi A. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2000 July; 19(7): 710-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10930822&dopt=Abstract
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Safety and efficacy of atorvastatin in heart transplant recipients. Author(s): Patel DN, Pagani FD, Koelling TM, Dyke DB, Baliga RR, Cody RJ, Lake KD, Aaronson KD. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2002 February; 21(2): 204-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11834348&dopt=Abstract
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Safety of HMG-CoA reductase inhibitors: focus on atorvastatin. Author(s): Bernini F, Poli A, Paoletti R. Source: Cardiovascular Drugs and Therapy / Sponsored by the International Society of Cardiovascular Pharmacotherapy. 2001; 15(3): 211-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11713888&dopt=Abstract
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Safety of low-density lipoprotein cholestrol reduction with atorvastatin versus simvastatin in a coronary heart disease population (the TARGET TANGIBLE trial). Author(s): Marz W, Wollschlager H, Klein G, Neiss A, Wehling M. Source: The American Journal of Cardiology. 1999 July 1; 84(1): 7-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10404843&dopt=Abstract
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Safety profile of atorvastatin-treated patients with low LDL-cholesterol levels. Author(s): Bakker-Arkema RG, Nawrocki JW, Black DM. Source: Atherosclerosis. 2000 March; 149(1): 123-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10704623&dopt=Abstract
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Short term effect of atorvastatin and vitamin E on serum levels of C3, a sensitive marker of the risk of myocardial infarction in men. Author(s): Muscari A, Bastagi L, Poggiopollini G, Tomassetti V, Massarelli G, Boni P, Puddu P. Source: Cardiovascular Drugs and Therapy / Sponsored by the International Society of Cardiovascular Pharmacotherapy. 2001 September; 15(5): 453-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11855664&dopt=Abstract
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Short-term atorvastatin treatment improves endothelial function in hypercholesterolemic women. Author(s): Marchesi S, Lupattelli G, Siepi D, Schillaci G, Vaudo G, Roscini AR, Sinzinger H, Mannarino E. Source: Journal of Cardiovascular Pharmacology. 2000 November; 36(5): 617-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11065222&dopt=Abstract
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Short-term effect of atorvastatin (80 mg) on plasma lipids of patients with unstable angina pectoris or non-Q-wave acute myocardial infarction. Author(s): Correia LC, Sposito AC, Passos LC, Lima JC, Braga JC, Rocha MS, Esteves JP, D'Oliveira A Jr. Source: The American Journal of Cardiology. 2002 July 15; 90(2): 162-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12106850&dopt=Abstract
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Short-term effect of atorvastatin in hypercholesterolaemic renal-transplant patients unresponsive to other statins. Author(s): Romero R, Calvino J, Rodriguez J, Sanchez-Guisande D. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2000 September; 15(9): 1446-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10978406&dopt=Abstract
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Short-term effects of atorvastatin on C-reactive protein. Author(s): Riesen WF, Engler H, Risch M, Korte W, Noseda G. Source: European Heart Journal. 2002 May; 23(10): 794-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12009719&dopt=Abstract
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Similar effects of atorvastatin, simvastatin and pravastatin on thrombogenic and inflammatory parameters in patients with hypercholesterolemia. Author(s): Joukhadar C, Klein N, Prinz M, Schrolnberger C, Vukovich T, Wolzt M, Schmetterer L, Dorner GT. Source: Thrombosis and Haemostasis. 2001 January; 85(1): 47-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11204586&dopt=Abstract
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Strong decrease of high sensitivity C-reactive protein with high-dose atorvastatin in patients with type 2 diabetes mellitus. Author(s): van de Ree MA, Huisman MV, Princen HM, Meinders AE, Kluft C; DALIStudy Group. Source: Atherosclerosis. 2003 January; 166(1): 129-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12482559&dopt=Abstract
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Systemic cause of unstable atherosclerotic plaques. Atorvastatin and Thrombogenicity of Carotid Atherosclerotic Plaque (ATROCAP) study group. Author(s): Cortellaro M, Cofrancesco E, Arbustini E, Gabrielli L, Tremoli E. Source: Lancet. 2000 April 15; 355(9212): 1362-3; Author Reply 1363-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10776765&dopt=Abstract
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The cost of reaching National Cholesterol Education Program (NCEP) goals in hypercholesterolaemic patients. A comparison of atorvastatin, simvastatin, lovastatin and fluvastatin. Author(s): Koren MJ, Smith DG, Hunninghake DB, Davidson MH, McKenney JM, Weiss SR, Schrott HG, Henley RW Jr, Tresh P, McLain RW, Bakker-Arkema RG, Black DM. Source: Pharmacoeconomics. 1998 July; 14(1): 59-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10182195&dopt=Abstract
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The discovery and development of atorvastatin, a potent novel hypolipidemic agent. Author(s): Roth BD. Source: Prog Med Chem. 2002; 40: 1-22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12516521&dopt=Abstract
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The effect of aggressive versus standard lipid lowering by atorvastatin on diabetic dyslipidemia: the DALI study: a double-blind, randomized, placebo-controlled trial in patients with type 2 diabetes and diabetic dyslipidemia. Author(s): Diabetes Atorvastin Lipid Intervention (DALI) Study Group. Source: Diabetes Care. 2001 August; 24(8): 1335-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11473066&dopt=Abstract
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The effect of atorvastatin on erythrocyte membranes and serum lipids in patients with type-2 hypercholesterolemia. Author(s): Koter M, Broncel M, Chojnowska-Jezierska J, Klikczynska K, Franiak I. Source: European Journal of Clinical Pharmacology. 2002 November; 58(8): 501-6. Epub 2002 September 28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12451426&dopt=Abstract
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The effect of atorvastatin on postprandial lipaemia in overweight or obese women homozygous for apo E3. Author(s): Vansant G, Mertens A, Muls E. Source: Acta Cardiol. 2001 June; 56(3): 149-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11471927&dopt=Abstract
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The effect of atorvastatin on serum lipids and lipoproteins in patients with homozyous familial hypercholesterolemia undergoing LDL-apheresis therapy. Author(s): Yamamoto A, Harada-Shiba M, Kawaguchi A, Oi K, Kubo H, Sakai S, Mikami Y, Imai T, Ito T, Kato H, Endo M, Sato I, Suzuki Y, Hori H. Source: Atherosclerosis. 2000 November; 153(1): 89-98. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11058703&dopt=Abstract
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The effect of atorvastatin on serum lipids, lipoprotein(a) and plasma fibrinogen levels in primary dyslipidaemia--a pilot study involving serial sampling. Author(s): Goudevenos JA, Bairaktari ET, Chatzidimou KG, Milionis HJ, Mikhailidis DP, Elisaf MS. Source: Current Medical Research and Opinion. 2001; 16(4): 269-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11268711&dopt=Abstract
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The effect of atorvastatin on serum lipids, lipoproteins and NMR spectroscopy defined lipoprotein subclasses in type 2 diabetic patients with ischaemic heart disease. Author(s): Soedamah-Muthu SS, Colhoun HM, Thomason MJ, Betteridge DJ, Durrington PN, Hitman GA, Fuller JH, Julier K, Mackness MI, Neil HA; CARDS Investigators. Source: Atherosclerosis. 2003 April; 167(2): 243-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12818407&dopt=Abstract
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The effect of pravastatin and atorvastatin on coenzyme Q10. Author(s): Bleske BE, Willis RA, Anthony M, Casselberry N, Datwani M, Uhley VE, Secontine SG, Shea MJ. Source: American Heart Journal. 2001 August; 142(2): E2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11479481&dopt=Abstract
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The effect of short-term lipid lowering with atorvastatin on carotid artery intima media thickness in patients with peripheral vascular disease: a pilot study. Author(s): Davis M, Atwal AS, Nair DR, Jagroop IA, Seifalian AM, Mikhailidis DP, Hamilton G. Source: Current Medical Research and Opinion. 2000; 16(3): 198-204. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11191010&dopt=Abstract
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The effects of concurrent atorvastatin therapy on the pharmacokinetics of intravenous midazolam. Author(s): Mc Donnell CG, Harte S, O'Driscoll J, O'Loughlin C, Van Pelt FD, Shorten GD. Source: Anaesthesia. 2003 September; 58(9): 899-904. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12911366&dopt=Abstract
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The effects of converting from simvastatin to atorvastatin on plasminogen activator inhibitor type-1. Author(s): Ito MK. Source: Journal of Clinical Pharmacology. 2001 July; 41(7): 779-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11452711&dopt=Abstract
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The efficacy of atorvastatin in treating patients with hypercholesterolaemia to target LDL-cholesterol goals: the LIPI-GOAL trial. Author(s): Muls E, De Backer G, Brohet C, Heller F; LIPI-GOAL investigators. Source: Acta Cardiol. 2001 April; 56(2): 109-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11357922&dopt=Abstract
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The genotoxicity profile of atorvastatin, a new drug in the treatment of hypercholesterolemia. Author(s): Ciaravino V, Kropko ML, Rothwell CE, Hovey CA, Theiss JC. Source: Mutation Research. 1995 June; 343(2-3): 95-107. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7791813&dopt=Abstract
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The GREek Atorvastatin and Coronary-heart-disease Evaluation (GREACE) study. Author(s): Mikhailidis DP, Wierzbicki AS. Source: Current Medical Research and Opinion. 2002; 18(4): 215-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12201622&dopt=Abstract
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The lipid-lowering effects of atorvastatin, a new HMG-CoA reductase inhibitor: results of a randomized, double-masked study. Author(s): Heinonen TM, Stein E, Weiss SR, McKenney JM, Davidson M, Shurzinske L, Black DM. Source: Clinical Therapeutics. 1996 September-October; 18(5): 853-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8930429&dopt=Abstract
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The metabolism of clopidogrel is catalyzed by human cytochrome P450 3A and is inhibited by atorvastatin. Author(s): Clarke TA, Waskell LA. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 2003 January; 31(1): 53-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12485953&dopt=Abstract
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Tolerance and pharmacokinetics of single-dose atorvastatin, a potent inhibitor of HMG-CoA reductase, in healthy subjects. Author(s): Posvar EL, Radulovic LL, Cilla DD Jr, Whitfield LR, Sedman AJ. Source: Journal of Clinical Pharmacology. 1996 August; 36(8): 728-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8877677&dopt=Abstract
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Toxic epidermal necrolysis from atorvastatin. Author(s): Pfeiffer CM, Kazenoff S, Rothberg HD. Source: Jama : the Journal of the American Medical Association. 1998 May 27; 279(20): 1613-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9613909&dopt=Abstract
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Treating patients with documented atherosclerosis to National Cholesterol Education Program-recommended low-density-lipoprotein cholesterol goals with atorvastatin, fluvastatin, lovastatin and simvastatin. Author(s): Brown AS, Bakker-Arkema RG, Yellen L, Henley RW Jr, Guthrie R, Campbell CF, Koren M, Woo W, McLain R, Black DM. Source: Journal of the American College of Cardiology. 1998 September; 32(3): 665-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9741509&dopt=Abstract
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Treating to meet NCEP-recommended LDL cholesterol concentrations with atorvastatin, fluvastatin, lovastatin, or simvastatin in patients with risk factors for coronary heart disease. Author(s): Hunninghake D, Bakker-Arkema RG, Wigand JP, Drehobl M, Schrott H, Early JL, Abdallah P, McBride S, Black DM. Source: The Journal of Family Practice. 1998 November; 47(5): 349-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9834769&dopt=Abstract
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Treatment of heterozygous familial hypercholesterolemia: atorvastatin vs simvastatin. Author(s): Bo M, Nicolello MT, Fiandra U, Mercadante G, Piliego T, Fabris F. Source: Nutr Metab Cardiovasc Dis. 2001 February; 11(1): 17-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11383320&dopt=Abstract
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Treatment of relapsing paralysis in experimental encephalomyelitis by targeting Th1 cells through atorvastatin. Author(s): Aktas O, Waiczies S, Smorodchenko A, Dorr J, Seeger B, Prozorovski T, Sallach S, Endres M, Brocke S, Nitsch R, Zipp F. Source: The Journal of Experimental Medicine. 2003 March 17; 197(6): 725-33. Epub 2003 Mar 10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12629065&dopt=Abstract
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Treatment with atorvastatin improves small artery compliance in patients with severe hypercholesterolemia. Author(s): Leibovitz E, Hazanov N, Zimlichman R, Shargorodsky M, Gavish D. Source: American Journal of Hypertension : Journal of the American Society of Hypertension. 2001 November; 14(11 Pt 1): 1096-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11724206&dopt=Abstract
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Treatment with atorvastatin to the National Cholesterol Educational Program goal versus 'usual' care in secondary coronary heart disease prevention. The GREek Atorvastatin and Coronary-heart-disease Evaluation (GREACE) study. Author(s): Athyros VG, Papageorgiou AA, Mercouris BR, Athyrou VV, Symeonidis AN, Basayannis EO, Demitriadis DS, Kontopoulos AG. Source: Current Medical Research and Opinion. 2002; 18(4): 220-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12201623&dopt=Abstract
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Use of atorvastatin in hyperlipidemic hypertensive renal transplant recipients. Author(s): Krmar RT, Ferraris JR, Ramirez JA, Sorroche P, Legal S, Cayssials A. Source: Pediatric Nephrology (Berlin, Germany). 2002 July; 17(7): 540-3. Epub 2002 May 25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12172771&dopt=Abstract
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Usefulness of quinapril and irbesartan to improve the anti-inflammatory response of atorvastatin and aspirin in patients with coronary heart disease. Author(s): Lauten WB, Khan QA, Rajagopalan S, Lerakis S, Rahman ST, Parthasarathy S, Khan BV. Source: The American Journal of Cardiology. 2003 May 1; 91(9): 1116-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12714159&dopt=Abstract
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Weekly versus daily dosing of atorvastatin. Author(s): Iliff RD. Source: The Journal of Family Practice. 2002 April; 51(4): 365-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11978260&dopt=Abstract
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CHAPTER 2. NUTRITION AND ATORVASTATIN Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and atorvastatin.
Finding Nutrition Studies on Atorvastatin 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 “atorvastatin” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.
7 Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.
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The following is a typical result when searching for recently indexed consumer information on atorvastatin: •
3-hydroxy-3-methylglutaryl coenzyme A reductase-independent inhibition of CD40 expression by atorvastatin in human endothelial cells. Author(s): Department of Cardiovascular Physiology, University of Goettingen, Goettingen, Germany. Source: Wagner, A H Gebauer, M Guldenzoph, B Hecker, M Arterioscler-Thromb-VascBiol. 2002 November 1; 22(11): 1784-9 1524-4636
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A preliminary evaluation of neural network analysis for pharmacodynamic modeling of the dosing of the hydroxymethylglutaryl coenzyme A-reductase inhibitors simvastatin and atorvastatin. Author(s): Department of Physiology and Pharmacology, Thomas J. Long School of Pharmacy and Health Sciences, University of the Pacific, Stockton, California 95211, USA. Source: Moon, A Smith, T Clin-Ther. 2002 April; 24(4): 653-61 0149-2918
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A randomized, double-blind, placebo-controlled, 8-week study to evaluate the efficacy and safety of once daily atorvastatin (10 mg) in patients with elevated LDLcholesterol. Author(s): Division of Cardiology, Taichung Veterans General Hospital, Chung-San Medical and Dental College, Taiwan. Source: Wang K, Y Ting C, T Jpn-Heart-J. 2001 November; 42(6): 725-38 0021-4868
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Aggressive LDL-cholesterol lowering with atorvastatin results in regression of atherosclerosis. Source: Anonymous Cardiovasc-J-S-Afr. 2001 Feb-March; 12(1): 56 1015-9657
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Aggressive lipid lowering does not improve endothelial function in type 2 diabetes: the Diabetes Atorvastatin Lipid Intervention (DALI) Study: a randomized, doubleblind, placebo-controlled trial. Author(s): Julius Center for General Practice and Patient Oriented Research and Department of Medicine, University Medical Center Utrecht, Utrecht, The Netherlands. Source: van Venrooij, F V van de Ree, M A Bots, M L Stolk, R P Huisman, M V Banga, J D Diabetes-Care. 2002 July; 25(7): 1211-6 0149-5992
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ARBITER: Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol: a randomized trial comparing the effects of atorvastatin and pravastatin on carotid intima medial thickness. Author(s): Cardiology Service, Walter Reed Army Medical Center, Washington, DC 20307-5001, and USA.
[email protected] Source: Taylor, A J Kent, S M Flaherty, P J Coyle, L C Markwood, T T Vernalis, M N Circulation. 2002 October 15; 106(16): 2055-60 1524-4539
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Atorvastatin (Lipitor). Author(s): Department of Pharmacy Services, Hartford Hospital, USA. Source: Tucker, G Conn-Med. 1998 May; 62(5): 283-5 0010-6178
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Atorvastatin activates PPAR-gamma and attenuates the inflammatory response in human monocytes. Author(s): Department of Medicine, Lund University, University Hospital MAS, Malmo, Sweden.
[email protected] Source: Grip, O Janciauskiene, S Lindgren, S Inflamm-Res. 2002 February; 51(2): 58-62 1023-3830
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Atorvastatin and micronized fenofibrate alone and in combination in type 2 diabetes with combined hyperlipidemia. Author(s): Lipid Out-patient Clinic, Aristotelian University, Hippocration Hospital, Thessaloniki, Greece.
[email protected] Source: Athyros, V G Papageorgiou, A A Athyrou, V V Demitriadis, D S Kontopoulos, A G Diabetes-Care. 2002 July; 25(7): 1198-202 0149-5992
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Atorvastatin compared with simvastatin-based therapies in the management of severe familial hyperlipidaemias. Author(s): Department of Chemical Pathology, St Thomas' Hospital, London, UK.
[email protected] Source: Wierzbicki, A S Lumb, P J Semra, Y Chik, G Christ, E R Crook, M A QJM. 1999 July; 92(7): 387-94 1460-2725
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Atorvastatin for the management of Type 2 diabetic patients with dyslipidaemia. A mid-term (9 months) treatment experience. Author(s): Diabetology Dept. Monfalcone and Gorizia, Monfalcone (GO), Italy. Source: Velussi, M Cernigoi, A M Tortul, C Merni, M Diabetes-Nutr-Metab. 1999 December; 12(6): 407-12 0394-3402
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Atorvastatin in the treatment of primary hypercholesterolemia and mixed dyslipidemias. Author(s): Pharmacy Service, Department of Veterans Affairs Medical Center, San Francisco, CA 94121, USA. Source: Yee, H S Fong, N T Ann-Pharmacother. 1998 October; 32(10): 1030-43 1060-0280
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Atorvastatin increases ecNOS levels in human platelets of hyperlipidemic subjects. Author(s): Cardiology and Atherosclerosis Research Group, School of Physical Sciences, Chemistry and Biochemistry, University of Windsor, Ontario, Canada. Source: Tannous, M Cheung, R Vignini, A Mutus, B Thromb-Haemost. 1999 November; 82(5): 1390-4 0340-6245
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Atorvastatin inhibits hypercholesterolemia-induced cellular proliferation and bone matrix production in the rabbit aortic valve. Author(s): Division of Cardiology, Department of Medicine, Northwestern University Medical School, Chicago, Ill 60611, USA.
[email protected] Source: Rajamannan, Nalini M Subramaniam, Malayannan Springett, Margaret Sebo, Thomas C Niekrasz, Marek McConnell, Joseph P Singh, Ravinder J Stone, Neil J Bonow, Robert O Spelsberg, Thomas C Circulation. 2002 June 4; 105(22): 2660-5 1524-4539
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Atorvastatin is not cataractogenic in beagle dogs. Author(s): Department of Pathology and Experimental Toxicology, Parke-Davis Pharmaceutical Research, Division of Warner Lambert Co., Ann Arbor, MI, USA.
[email protected] Source: Robertson, D G Urda, E R Rothwell, C E Walsh, K M Curr-Eye-Res. 1997 December; 16(12): 1229-35 0271-3683
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Atorvastatin reduces postprandial accumulation and cholesteryl ester transfer protein-mediated remodeling of triglyceride-rich lipoprotein subspecies in type IIb hyperlipidemia. Author(s): Institut National de la Sante et de la Recherche Medicale (INSERM) Unite 551, Dyslipoproteinemia and Atherosclerosis, Hopital de la Pitie, Pavillon Benjamin Delessert, 83 boulevard de l'hopital, 75651 Paris Cedex 13, France.
[email protected] Source: Guerin, M Egger, P Le Goff, W Soudant, C Dupuis, R Chapman, M J J-ClinEndocrinol-Metab. 2002 November; 87(11): 4991-5000 0021-972X
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Atorvastatin therapy in hypercholesterolemic patients suppresses cellular uptake of oxidized-LDL by differentiating monocytes. Author(s): The Lipid Research Laboratory, Technion Faculty of Medicine, The Rappaport Family Institute for Research in the Medical Sciences and Rambam Medical Center, 31096, Haifa, Israel.
[email protected] Source: Fuhrman, B Koren, L Volkova, N Keidar, S Hayek, T Aviram, M Atherosclerosis. 2002 September; 164(1): 179-85 0021-9150
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Atorvastatin treatment induced peroxisome proliferator-activated receptor alpha expression and decreased plasma nonesterified fatty acids and liver triglyceride in fructose-fed rats. Author(s): Unidad de Farmacologia y Farmacognosia, Facultad de Farmacia, Universidad de Barcelona, Avenida Diagonal 643, 08028 Barcelona, Spain. Source: Roglans, Nuria Sanguino, Elena Peris, Cristina Alegret, Marta Vazquez, Manuel Adzet, Tomas Diaz, Cristina Hernandez, Gonzalo Laguna, Juan C Sanchez, Rosa M JPharmacol-Exp-Ther. 2002 July; 302(1): 232-9 0022-3565
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Atorvastatin treatment prevents alterations in coronary smooth muscle nuclear Ca2+ signaling in diabetic dyslipidemia. Author(s): Department of Physiology, School of Medicine, University of Missouri, Columbia 65212, USA. Source: Wamhoff, B R Dixon, J L Sturek, M J-Vasc-Res. 2002 May-June; 39(3): 208-20 1018-1172
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Atorvastatin. Author(s): University College Hospitals, Middlesex Hospital, London. Source: Hyatt, P J Br-J-Hosp-Med. 1997 October 1-14; 58(7): 333-6 0007-1064
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Beneficial effects of atorvastatin in the treatment of hyperlipidemia after renal transplantation. Author(s): Klinische Abteilung fur Nephrologie und Dialyse, Universitatsklinik fur Innere Medizin III, Allgemeines Krankenhaus der Stadt Wien, Vienna, Austria. Source: Demetriou, D Shabpar, A Bohmig, G Schmaldienst, S Horl, W H Watschinger, B Wien-Klin-Wochenschr. 2000 April 21; 112(8): 358-61 0043-5325
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Bilateral pharmacokinetic interaction between cyclosporine A and atorvastatin in renal transplant recipients. Author(s): Medical Department, The National Hospital, Oslo, Norway.
[email protected] Source: Asberg, A Hartmann, A Fjeldsa, E Bergan, S Holdaas, H Am-J-Transplant. 2001 November; 1(4): 382-6 1600-6135
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By the way, doctor. My hair has been thinning out for the past decade or so, but since my doctor started me on Lipitor (atorvastatin) a few months ago for high cholesterol, I swear it's been falling out much faster. My doctor discounts the possibility, but I looked in the Physicians' desk reference (PDR) and alopecia is listed under “adverse reactions.” What do you think? Source: Lee, T H Harv-Health-Lett. 2000 July; 25(9): 8 1052-1577
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Cerivastatin and atorvastatin inhibit IL-3-dependent differentiation and IgEmediated histamine release in human basophils and downmodulate expression of the basophil-activation antigen CD203c/E-NPP3. Author(s): Department of Internal Medicine I, Division of Hematology & Hemostaseology, University of Vienna, Wahringer Gurtel 18-20, A-1090 Vienna, Austria.
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Source: Majlesi, Y Samorapoompichit, P Hauswirth, A W Schernthaner, G H Ghannadan, M Baghestanian, M Rezaie Majd, A Valenta, R Sperr, W R Buhring, H J Valent, P J-Leukoc-Biol. 2003 January; 73(1): 107-17 0741-5400 •
Comparative efficacy study of atorvastatin vs simvastatin, pravastatin, lovastatin and placebo in type 2 diabetic patients with hypercholesterolaemia. Author(s): Department of Geriatrics and Metabolic Diseases, Second University of Naples, Italy.
[email protected] Source: Gentile, S Turco, S Guarino, G Sasso, C F Amodio, M Magliano, P Salvatore, T Corigliano, G Agrusta, M De Simone, G Gaeta, I Oliviero, B Torella, R Diabetes-ObesMetab. 2000 December; 2(6): 355-62 1462-8902
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Comparing the efficacy and safety of atorvastatin and simvastatin in Asians with elevated low-density lipoprotein-cholesterol--a multinational, multicenter, doubleblind study. Author(s): Department of Internal Medicine (Cardiology Section), National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei, Taiwan. Source: Wu, C C Sy, R Tanphaichitr, V Hin, A T Suyono, S Lee, Y T J-Formos-MedAssoc. 2002 July; 101(7): 478-87 0929-6646
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Comparison of atorvastatin alone versus simvastatin +/- cholestyramine in the management of severe primary hypercholesterolaemia (the six cities study). Author(s): Lipid Research Department, St Vincent's Hospital, Darlinghurst, NSW. Source: Simons, L A Aust-N-Z-J-Med. 1998 June; 28(3): 327-33 0004-8291
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Comparison of extended-release niacin and atorvastatin monotherapies and combination treatment of the atherogenic lipid profile in diabetes mellitus. Author(s): Diabetes Research Center, Tustin, California 92780, USA. Source: Van, Joanne T Pan, Jianqiu Wasty, Talat Chan, Eve Wu, Xiaoshan Charles, M Arthur Am-J-Cardiol. 2002 June 1; 89(11): 1306-8 0002-9149
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Comparison of the effects of atorvastatin or fenofibrate on nonlipid biochemical risk factors and the LDL particle size in subjects with combined hyperlipidemia. Author(s): Third Department of Internal Medicine, General University Hospital, Charles University, Prague, Czech Republic.
[email protected] Source: Melenovsky, V Malik, J Wichterle, D Simek, J Pisarikova, A Skrha, J Poledne, R Stavek, P Ceska, R Am-Heart-J. 2002 October; 144(4): E6 1097-6744
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Comparison of the effects of atorvastatin versus simvastatin on subclinical atherosclerosis in primary preventionas determined by electronbeam tomography. Author(s): Beth Israel Medical Center, New York, New York, USA.
[email protected] Source: Hecht, H S Harman, S M Am-J-Cardiol. 2003 January 1; 91(1): 42-5 0002-9149
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Dose-dependent action of atorvastatin in type IIB hyperlipidemia: preferential and progressive reduction of atherogenic apoB-containing lipoprotein subclasses (VLDL2, IDL, small dense LDL) and stimulation of cellular cholesterol efflux. Author(s): Institut National de la Sante et de la Recherche Medicale (INSERM Unite 551), Hopital de la Pitie, Pavillon Benjamin Delessert, 83 Boulevard de l'Hopital, 75651 Paris, Cedex 13, France.
[email protected] Source: Guerin, M Egger, P Soudant, C Le Goff, W van Tol, A Dupuis, R Chapman, M J Atherosclerosis. 2002 August; 163(2): 287-96 0021-9150
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Dose-response effects of atorvastatin and simvastatin on high-density lipoprotein cholesterol in hypercholesterolaemic patients: a review of five comparative studies. Author(s): Department of Chemical Pathology, St. Thomas' Hospital, Lambeth Palace Road, SE1 7EH, London, UK. Source: Wierzbicki, A S Mikhailidis, D P Int-J-Cardiol. 2002 July; 84(1): 53-7 0167-5273
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Effect of atorvastatin (80 mg) initiated at the time of coronary artery stent implantation on C-reactive protein and six-month clinical events. Author(s): Cattedra di Cardiochirurgia, Universita Tor Vergata, Rome, Italy.
[email protected] Source: Gaspardone, A Versaci, F Proietti, I Tomai, F Altamura, L Skossyreva, O Chiariello, L Am-J-Cardiol. 2002 October 1; 90(7): 786-9 0002-9149
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Effect of atorvastatin and bezafibrate on plasma levels of C-reactive protein in combined (mixed) hyperlipidemia. Author(s): Biochemistry Service, Fundacion Jimenez Diaz, Avda. Reyes Catolicos, 2, 28040, Madrid, Spain.
[email protected] Source: Gomez Gerique, J A Ros, E Olivan, J Mostaza, J M Vilardell, M Pinto, X Civeira, F Hernandez, A da Silva, P M Rodriguez Botaro, A Zambon, D Lima, J Diaz, C Aristegui, R Sol, J M Chaves, J Hernandez, G Atherosclerosis. 2002 June; 162(2): 245-51 0021-9150
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Effect of atorvastatin on chylomicron remnant metabolism in visceral obesity: a study employing a new stable isotope breath test. Author(s): University Department of Medicine, Royal Perth Hospital, GPO Box X2213, Perth, Western Australia 6847, Australia. Source: Chan, D C Watts, G F Barrett, P H Martins, I J James, A P Mamo, J C Mori, T A Redgrave, T G J-Lipid-Res. 2002 May; 43(5): 706-12 0022-2275
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Effect of atorvastatin on endothelium-dependent vasodilation in postmenopausal women with average serum cholesterol levels. Author(s): Department of Cardiovascular Sciences, University of Cagliari, Sardinia, Italy. Source: Mercuro, G Zoncu, S Saiu, F Sarais, C Rosano, G M Am-J-Cardiol. 2002 October 1; 90(7): 747-50 0002-9149
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Effect of atorvastatin on high-density lipoprotein apolipoprotein A-I production and clearance in the New Zealand white rabbit. Author(s): Department of Medicine, Division of Endocrinology, University of Toronto, Toronto, Canada. Source: Rashid, S Uffelman, K D Barrett, P H Lewis, G F Circulation. 2002 December 3; 106(23): 2955-60 1524-4539
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Effects of atorvastatin (and blood pressure lowering comparing amlodipide-based therapy with beta-blocker-based therapy) on serum variables of cholesterol synthesis and absorption, thrombogenicity and on low-density lipoprotein oxidation in vivo. Author(s): Department of Medicine, Division of Cardiology, Helsinki University Hospital, Haartmaininkatu 4, 00290 Helsinki, Finland. Source: Nieminen, M S Viikari, J Ahotupa, M Vasankari, T Kantola, I Strandberg, T Vanhanen, H J-Hum-Hypertens. 2001 August; 15 Suppl 1: S27-9 0950-9240
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Effects of atorvastatin 80 mg daily early after onset of unstable angina pectoris or non-Q-wave myocardial infarction. Author(s): Division of Cardiology, S. Filippo Neri Hospital, Rome, Italy.
[email protected] Source: Colivicchi, F Guido, V Tubaro, M Ammirati, F Montefoschi, N Varveri, A Santini, M Am-J-Cardiol. 2002 October 15; 90(8): 872-4 0002-9149
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Effects of atorvastatin and omega-3 fatty acids on LDL subfractions and postprandial hyperlipemia in patients with combined hyperlipemia. Author(s): Department of Medicine, Institute of Clinical Medicine, University of Tromso, Norway.
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Source: Nordoy, A Hansen, J B Brox, J Svensson, B Nutr-Metab-Cardiovasc-Dis. 2001 February; 11(1): 7-16 0939-4753 •
Effects of atorvastatin on aortic pulse wave velocity in patients with hypertension and hypercholesterolaemia: a preliminary study. Author(s): Department of Internal Medicine, Broussaia Hospital, Paris, France. Source: Raison, J Rudnichi, A Safar, M E J-Hum-Hypertens. 2002 October; 16(10): 705-10 0950-9240
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Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes. The MIRACL study. Source: Anonymous Indian-Heart-J. 2001 Mar-April; 53(2): 237 0019-4832
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Effects of atorvastatin on fasting and postprandial lipoprotein subclasses in coronary heart disease patients versus control subjects. Author(s): Atherosclerosis Research Laboratory, Lipid and Heart Disease Prevention Clinic, Department of Medicine, New England Medical Center, Tufts University School of Medicine, Boston, Massachusetts, USA.
[email protected] Source: Schaefer, E J McNamara, J R Tayler, T Daly, J A Gleason, J A Seman, L J Ferrari, A Rubenstein, J J Am-J-Cardiol. 2002 October 1; 90(7): 689-96 0002-9149
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Effects of atorvastatin on stroke in patients with unstable angina or non-Q-wave myocardial infarction: a Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) substudy. Author(s): Division of Cardiology, San Francisco General Hospital, and the University of California, San Francisco School of Medicine, San Francisco, Calif 94110, USA.
[email protected] Source: Waters, D D Schwartz, G G Olsson, A G Zeiher, A Oliver, M F Ganz, P Ezekowitz, M Chaitman, B R Leslie, S J Stern, T Circulation. 2002 September 24; 106(13): 1690-5 1524-4539
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Effects of low doses of simvastatin and atorvastatin on high-density lipoprotein cholesterol levels in patients with hypercholesterolemia. Author(s): Department of Internal Medicine, University of Milan, Maggiore Hospital IRCCS, Italy.
[email protected] Source: Branchi, A Fiorenza, A M Torri, A Muzio, F Berra, C Colombo, E Dalla Valle, E Rovellini, A Sommariva, D Clin-Ther. 2001 June; 23(6): 851-7 0149-2918
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Effects of rosiglitazone alone and in combination with atorvastatin on the metabolic abnormalities in type 2 diabetes mellitus. Author(s): GlaxoSmithKline, Collegeville, Pennsylvania 19426, USA.
[email protected] Source: Freed, M I Ratner, R Marcovina, S M Kreider, M M Biswas, N Cohen, B R Brunzell, J D Am-J-Cardiol. 2002 November 1; 90(9): 947-52 0002-9149
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Effects of short-term atorvastatin treatment on global fibrinolytic capacity, and sLselectin and sFas levels in hyperlipidemic patients with coronary artery disease. Author(s): Department of Cardiology, Hacettepe University School of Medicine, Ankara, Turkey.
[email protected] Source: Atalar, E Ozmen, F Haznedaroglu, I Acil, T Ozer, N Ovunc, K Aksoyek, S Kes, S Int-J-Cardiol. 2002 August; 84(2-3): 227-31 0167-5273
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Efficacy and safety of atorvastatin 10 mg every other day in hypercholesterolemia. Author(s): Department of Medicine, Phramongkutklao College of Medicine, Bangkok, Thailand.
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Source: Piamsomboon, Chumpol Laothavorn, Prasart Saguanwong, Sopon Chatlaong, Boonsert Nasawadi, Chanarong Tanprasert, Pravit Pongsiri, Kittika J-Med-Assoc-Thai. 2002 March; 85(3): 297-300 0125-2208 •
Efficacy of atorvastatin compared with simvastatin in patients with hypercholesterolemia. Author(s): Point Medical, Dijon, France. Source: Farnier, M Portal, J J Maigret, P J-Cardiovasc-Pharmacol-Ther. 2000 January; 5(1): 27-32 1074-2484
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Efficacy of atorvastatin in treating high risk patients to reach low density lipoproteincholesterol goals: the Treat to Target (TTT-Israel) Study. Author(s): Department of Internal Medicine A and Institute of Physiological Hygiene, Wolfson Medical Center, Holon, Israel. Source: Leibovitz, Eyal Harats, Dror Gavish, Dov Isr-Med-Assoc-J. 2002 June; 4(6): 40710 1565-1088
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Efficacy of combination of atorvastatin and micronised fenofibrate in the treatment of severe mixed hyperlipidemia. Author(s): Department of Internal Medicine, Medical School, University of Ioannina, Greece.
[email protected] Source: Kiortisis, D N Millionis, H Bairaktari, E Elisaf, M S Eur-J-Clin-Pharmacol. 2000 December; 56(9-10): 631-5 0031-6970
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Factorial study of the effects of atorvastatin and fish oil on dyslipidaemia in visceral obesity. Author(s): Department of Medicine, University of Western Australia, Western Australian Institute for Medical Research, Royal Perth Hospital, Perth, Western Australia. Source: Chan, D C Watts, G F Mori, T A Barrett, P H Beilin, L J Redgrave, T G Eur-JClin-Invest. 2002 June; 32(6): 429-36 0014-2972
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High doses of atorvastatin and simvastatin induce key enzymes involved in VLDL production. Source: Roglans, N. Verd, J.C. Peris, C. Alegret, M. Vazquez, M. Adzet, T. Diaz, C. Hernandez, G. Laguna, J.C. Sanchez, R.M. Lipids. Champaign, Ill. : American Oil Chemists' Society, 1966-. May 2002. volume 37 (5) page 445-454. 0024-4201
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High-dose atorvastatin therapy in severe heterozygous familial hypercholesterolaemia. Author(s): Department of Chemical Pathology, St. Thomas's Hospital, London, UK. Source: Wierzbicki, A S Lumb, P J Semra, Y K Crook, M A QJM. 1998 April; 91(4): 291-4 1460-2725
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Implications of the atorvastatin versus revascularization treatment (AVERT) study for the clinician. Author(s): Foothill Cardiology/California Heart Care, 2601 West Alameda Avenue, Suite 304, Burbank, CA 91505, USA.
[email protected] Source: Eisenberg, D Curr-Cardiol-Repage 2000 September; 2(5): 433-8 1523-3782
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Increased atherosclerosis in diabetic dyslipidemic swine: protection by atorvastatin involves decreased VLDL triglycerides but minimal effects on the lipoprotein profile. Author(s): Dalton Cardiovascular Research Center, University of Missouri, Research Park, Columbia, MO, USA.
[email protected] Source: Dixon, J L Shen, S Vuchetich, J P Wysocka, E Sun, G Y Sturek, M J-Lipid-Res. 2002 October; 43(10): 1618-29 0022-2275
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Induction of lipoprotein lipase gene expression in 3T3-L1 preadipocytes by atorvastatin, a cholesterol- and triglyceride-lowering drug. Author(s): Biomedical Sciences, University of Missouri-Columbia, Mo 65211, USA. Source: Bey, L Maigret, P Laouenan, H Hamilton, M T Pharmacology. 2002 September; 66(1): 51-6 0031-7012
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Influence of atorvastatin versus simvastatin on fibrinogen and other hemorheological parameters in patients with severe hypercholesterolemia treated with regular lowdensity lipoprotein immunoadsorption apheresis. Author(s): Medical Department II, Klinikum Grosshadern, University of Munich, Germany.
[email protected] Source: Otto, C Geiss, H C Donner, M G Parhofer, K G Schwandt, P Ther-Apher. 2000 June; 4(3): 244-8 1091-6660
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Is a mechanical or a metabolic approach superior in the treatment of coronary disease? Results of the atorvastatin versus revascularization (AVERT) trial. Source: Waters, D Eur-Heart-J. 2000 July; 21(13): 1029-31 0195-668X
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Is alternate daily dose of atorvastatin effective in treating patients with hyperlipidemia? The Alternate Day Versus Daily Dosing of Atorvastatin Study (ADDAS). Author(s): Department of Pharmacy, Veterans Administration Central California Health Care System, Fresno, Calif 93703, USA. Source: Matalka, M S Ravnan, M C Deedwania, P C Am-Heart-J. 2002 October; 144(4): 674-7 1097-6744
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Lipitor (atorvastatin calcium) tablets. Source: Claussen, D W Gastroenterol-Nurs. 1998 Sep-October; 21(5): 219-20 1042-895X
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Long term efficacy and safety of atorvastatin in the treatment of severe type III and combined dyslipidaemia. Author(s): Department of Vascular Medicine, Academic Medical Centre, University of Amsterdam, 1105 AZ Amsterdam, Netherlands. Source: van Dam, M Zwart, M de Beer, F Smelt, A H Prins, M H Trip, M D Havekes, L M Lansberg, P J Kastelein, J J Heart. 2002 September; 88(3): 234-8 1468-201X
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Long-term (18-month) efficacy of atorvastatin therapy in type 2 diabetics at cardiovascular risk. Author(s): Diabetic Clinic, Casa di Cura Pineta del Carso, Viale Stazione 26, 34011 Aurisina, TS, Italy.
[email protected] Source: Velussi, M Nutr-Metab-Cardiovasc-Dis. 2002 February; 12(1): 29-35 0939-4753
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Metabolism and excretion of atorvastatin in rats and dogs. Author(s): Department of Pharmacokinetics, Dynamics, and Metabolism, Parke-Davis Pharmaceutical Research Co., Ann Arbor, Michigan 48105, USA. Source: Black, A E Hayes, R N Roth, B D Woo, P Woolf, T F Drug-Metab-Dispos. 1999 August; 27(8): 916-23 0090-9556
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Possible short-term amelioration of basilar plaque by high-dose atorvastatin: use of reductase inhibitors for intracranial plaque stabilization. Author(s): Stroke Service, Centennial Medical Center, 2400 Patterson Street, Suite 123, Nashville, TN 37203, USA. Source: Callahan, A S 3rd Berger, B L Beuter, M J Devlin, T G J-Neuroimaging. 2001 April; 11(2): 202-4 1051-2284
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Proapoptotic effect of atorvastatin on stimulated rabbit smooth muscle cells. Author(s): Institute of Pharmacological Sciences, University of Milan, Milan, Italy.
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Source: Baetta, R Donetti, E Comparato, C Calore, M Rossi, A Teruzzi, C Paoletti, R Fumagalli, R Soma, M R Pharmacol-Res. 1997 August; 36(2): 115-21 1043-6618 •
Raman spectroscopic investigation of atorvastatin, amlodipine, and both on atherosclerotic plaque development in APOE*3 Leiden transgenic mice. Author(s): Department of Cardiology, C5-P, Leiden University Medical Center, P.O. Box 9600, 2300 RC, Leiden, The Netherlands. Source: van de Poll, S W Delsing, D J Jukema, J W Princen, H M Havekes, L M Puppels, G J van der Laarse, A Atherosclerosis. 2002 September; 164(1): 65-71 0021-9150
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Rhabdomyolysis associated with concomitant use of atorvastatin and cyclosporine. Author(s): College of Pharmacy and Allied Health Professions, St. John's University, Jamaica, NY 43210, USA. Source: Maltz, H C Balog, D L Cheigh, J S Ann-Pharmacother. 1999 November; 33(11): 1176-9 1060-0280
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Short term effect of atorvastatin and vitamin E on serum levels of C3, a sensitive marker of the risk of myocardial infarction in men. Author(s): Department of Internal Medicine, Cardioangiology, University of Bologna, Italy.
[email protected] Source: Muscari, A Bastagi, L Poggiopollini, G Tomassetti, V Massarelli, G Boni, P Puddu, P Cardiovasc-Drugs-Ther. 2001 September; 15(5): 453-8 0920-3206
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Short-term effects of atorvastatin on C-reactive protein. Author(s): Institute of Clinical Chemistry and Hematology, Kantonsspital, St. Gallen, Switzerland. Source: Riesen, W F Engler, H Risch, M Korte, W Noseda, G Eur-Heart-J. 2002 May; 23(10): 794-9 0195-668X
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Similar effects of atorvastatin, simvastatin and pravastatin on thrombogenic and inflammatory parameters in patients with hypercholesterolemia. Author(s): Department of Clinical Pharmacology, University of Vienna Medical School, Austria. Source: Joukhadar, C Klein, N Prinz, M Schrolnberger, C Vukovich, T Wolzt, M Schmetterer, L Dorner, G T Thromb-Haemost. 2001 January; 85(1): 47-51 0340-6245
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Simvastatin and atorvastatin enhance hypotensive effect of diltiazem in rats. Author(s): Department of Pharmacology, Hokkaido College of Pharmacy, 7-1 Katsuraoka, Otaru 047-0264, Japan. Source: Marumo, H Satoh, K Yamamoto, A Kaneta, S Ichihara, K Yakugaku-Zasshi. 2001 October; 121(10): 761-4 0031-6903
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The cost of reaching National Cholesterol Education Program (NCEP) goals in hypercholesterolaemic patients. A comparison of atorvastatin, simvastatin, lovastatin and fluvastatin. Author(s): Jacksonville Center for Clinical Research, Florida, USA. Source: Koren, M J Smith, D G Hunninghake, D B Davidson, M H McKenney, J M Weiss, S R Schrott, H G Henley, R W Tresh, P McLain, R W Bakker Arkema, R G Black, D M Pharmacoeconomics. 1998 July; 14(1): 59-70 1170-7690
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The effect of atorvastatin on postprandial lipaemia in overweight or obese women homozygous for apo E3. Author(s): Catholic University Leuven, University Hospital Gasthuisberg, Department of Endocrinology, Metabolism and Nutrition, Belgium.
[email protected] Source: Vansant, G Mertens, A Muls, E Acta-Cardiol. 2001 June; 56(3): 149-54 0001-5385
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The efficacy of atorvastatin in treating patients with hypercholesterolaemia to target LDL-cholesterol goals: the LIPI-GOAL trial. Author(s): Dienst Endocrinologie, Metabolisme en Voeding, Universitair Ziekenhuis Gasthuisberg, Leuven, Belgium.
[email protected] Source: Muls, E De Backer, G Brohet, C Heller, F Acta-Cardiol. 2001 April; 56(2): 109-14 0001-5385
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The HMG-CoA reductase inhibitor, atorvastatin, promotes a Th2 bias and reverses paralysis in central nervous system autoimmune disease. Author(s): Department of Neurology and Neurological Sciences, Beckman Center for Molecular Medicine, Stanford University, Stanford, California 94305, USA. Source: Youssef, S Stuve, O Patarroyo, J C Ruiz, P J Radosevich, J L Hur, E M Bravo, M Mitchell, D J Sobel, R A Steinman, L Zamvil, S S Nature. 2002 November 7; 420(6911): 78-84 0028-0836
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Treatment of heterozygous familial hypercholesterolemia: atorvastatin vs simvastatin. Author(s): Lipid Clinic, Department of Medical and Surgical Science, Section of Gerontology, University of Turin, Italy. Source: Bo, M Nicolello, M T Fiandra, U Mercadante, G Piliego, T Fabris, F Nutr-MetabCardiovasc-Dis. 2001 February; 11(1): 17-24 0939-4753
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Use of atorvastatin in hyperlipidemic hypertensive renal transplant recipients. Author(s): Department of Molecular Medicine, Karolinska Institutet, L3 Karolinska Hospital, 171 76 Stockholm, Sweden.
[email protected] Source: KrMarch, R T Ferraris, J R Ramirez, J A Sorroche, P Legal, S Cayssials, A PediatrNephrol. 2002 July; 17(7): 540-3 0931-041X
The following information is typical of that found when using the “Full IBIDS Database” to search for “atorvastatin” (or a synonym): •
3-hydroxy-3-methylglutaryl coenzyme A reductase-independent inhibition of CD40 expression by atorvastatin in human endothelial cells. Author(s): Department of Cardiovascular Physiology, University of Goettingen, Goettingen, Germany. Source: Wagner, A H Gebauer, M Guldenzoph, B Hecker, M Arterioscler-Thromb-VascBiol. 2002 November 1; 22(11): 1784-9 1524-4636
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A preliminary evaluation of neural network analysis for pharmacodynamic modeling of the dosing of the hydroxymethylglutaryl coenzyme A-reductase inhibitors simvastatin and atorvastatin. Author(s): Department of Physiology and Pharmacology, Thomas J. Long School of Pharmacy and Health Sciences, University of the Pacific, Stockton, California 95211, USA. Source: Moon, A Smith, T Clin-Ther. 2002 April; 24(4): 653-61 0149-2918
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A randomized, double-blind, placebo-controlled, 8-week study to evaluate the efficacy and safety of once daily atorvastatin (10 mg) in patients with elevated LDLcholesterol. Author(s): Division of Cardiology, Taichung Veterans General Hospital, Chung-San Medical and Dental College, Taiwan. Source: Wang K, Y Ting C, T Jpn-Heart-J. 2001 November; 42(6): 725-38 0021-4868
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Aggressive LDL-cholesterol lowering with atorvastatin results in regression of atherosclerosis. Source: Anonymous Cardiovasc-J-S-Afr. 2001 Feb-March; 12(1): 56 1015-9657
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Aggressive lipid lowering does not improve endothelial function in type 2 diabetes: the Diabetes Atorvastatin Lipid Intervention (DALI) Study: a randomized, doubleblind, placebo-controlled trial. Author(s): Julius Center for General Practice and Patient Oriented Research and Department of Medicine, University Medical Center Utrecht, Utrecht, The Netherlands. Source: van Venrooij, F V van de Ree, M A Bots, M L Stolk, R P Huisman, M V Banga, J D Diabetes-Care. 2002 July; 25(7): 1211-6 0149-5992
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ARBITER: Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol: a randomized trial comparing the effects of atorvastatin and pravastatin on carotid intima medial thickness. Author(s): Cardiology Service, Walter Reed Army Medical Center, Washington, DC 20307-5001, and USA.
[email protected] Source: Taylor, A J Kent, S M Flaherty, P J Coyle, L C Markwood, T T Vernalis, M N Circulation. 2002 October 15; 106(16): 2055-60 1524-4539
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Atorvastatin (Lipitor). Author(s): Department of Pharmacy Services, Hartford Hospital, USA. Source: Tucker, G Conn-Med. 1998 May; 62(5): 283-5 0010-6178
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Atorvastatin activates PPAR-gamma and attenuates the inflammatory response in human monocytes. Author(s): Department of Medicine, Lund University, University Hospital MAS, Malmo, Sweden.
[email protected] Source: Grip, O Janciauskiene, S Lindgren, S Inflamm-Res. 2002 February; 51(2): 58-62 1023-3830
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Atorvastatin and micronized fenofibrate alone and in combination in type 2 diabetes with combined hyperlipidemia. Author(s): Lipid Out-patient Clinic, Aristotelian University, Hippocration Hospital, Thessaloniki, Greece.
[email protected] Source: Athyros, V G Papageorgiou, A A Athyrou, V V Demitriadis, D S Kontopoulos, A G Diabetes-Care. 2002 July; 25(7): 1198-202 0149-5992
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Atorvastatin compared with simvastatin-based therapies in the management of severe familial hyperlipidaemias. Author(s): Department of Chemical Pathology, St Thomas' Hospital, London, UK.
[email protected] Source: Wierzbicki, A S Lumb, P J Semra, Y Chik, G Christ, E R Crook, M A QJM. 1999 July; 92(7): 387-94 1460-2725
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Atorvastatin for the management of Type 2 diabetic patients with dyslipidaemia. A mid-term (9 months) treatment experience. Author(s): Diabetology Dept. Monfalcone and Gorizia, Monfalcone (GO), Italy. Source: Velussi, M Cernigoi, A M Tortul, C Merni, M Diabetes-Nutr-Metab. 1999 December; 12(6): 407-12 0394-3402
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Atorvastatin in the treatment of primary hypercholesterolemia and mixed dyslipidemias. Author(s): Pharmacy Service, Department of Veterans Affairs Medical Center, San Francisco, CA 94121, USA. Source: Yee, H S Fong, N T Ann-Pharmacother. 1998 October; 32(10): 1030-43 1060-0280
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Atorvastatin increases ecNOS levels in human platelets of hyperlipidemic subjects. Author(s): Cardiology and Atherosclerosis Research Group, School of Physical Sciences, Chemistry and Biochemistry, University of Windsor, Ontario, Canada.
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Source: Tannous, M Cheung, R Vignini, A Mutus, B Thromb-Haemost. 1999 November; 82(5): 1390-4 0340-6245 •
Atorvastatin inhibits hypercholesterolemia-induced cellular proliferation and bone matrix production in the rabbit aortic valve. Author(s): Division of Cardiology, Department of Medicine, Northwestern University Medical School, Chicago, Ill 60611, USA.
[email protected] Source: Rajamannan, Nalini M Subramaniam, Malayannan Springett, Margaret Sebo, Thomas C Niekrasz, Marek McConnell, Joseph P Singh, Ravinder J Stone, Neil J Bonow, Robert O Spelsberg, Thomas C Circulation. 2002 June 4; 105(22): 2660-5 1524-4539
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Atorvastatin is not cataractogenic in beagle dogs. Author(s): Department of Pathology and Experimental Toxicology, Parke-Davis Pharmaceutical Research, Division of Warner Lambert Co., Ann Arbor, MI, USA.
[email protected] Source: Robertson, D G Urda, E R Rothwell, C E Walsh, K M Curr-Eye-Res. 1997 December; 16(12): 1229-35 0271-3683
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Atorvastatin reduces postprandial accumulation and cholesteryl ester transfer protein-mediated remodeling of triglyceride-rich lipoprotein subspecies in type IIb hyperlipidemia. Author(s): Institut National de la Sante et de la Recherche Medicale (INSERM) Unite 551, Dyslipoproteinemia and Atherosclerosis, Hopital de la Pitie, Pavillon Benjamin Delessert, 83 boulevard de l'hopital, 75651 Paris Cedex 13, France.
[email protected] Source: Guerin, M Egger, P Le Goff, W Soudant, C Dupuis, R Chapman, M J J-ClinEndocrinol-Metab. 2002 November; 87(11): 4991-5000 0021-972X
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Atorvastatin therapy in hypercholesterolemic patients suppresses cellular uptake of oxidized-LDL by differentiating monocytes. Author(s): The Lipid Research Laboratory, Technion Faculty of Medicine, The Rappaport Family Institute for Research in the Medical Sciences and Rambam Medical Center, 31096, Haifa, Israel.
[email protected] Source: Fuhrman, B Koren, L Volkova, N Keidar, S Hayek, T Aviram, M Atherosclerosis. 2002 September; 164(1): 179-85 0021-9150
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Atorvastatin treatment induced peroxisome proliferator-activated receptor alpha expression and decreased plasma nonesterified fatty acids and liver triglyceride in fructose-fed rats. Author(s): Unidad de Farmacologia y Farmacognosia, Facultad de Farmacia, Universidad de Barcelona, Avenida Diagonal 643, 08028 Barcelona, Spain. Source: Roglans, Nuria Sanguino, Elena Peris, Cristina Alegret, Marta Vazquez, Manuel Adzet, Tomas Diaz, Cristina Hernandez, Gonzalo Laguna, Juan C Sanchez, Rosa M JPharmacol-Exp-Ther. 2002 July; 302(1): 232-9 0022-3565
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Atorvastatin. Author(s): University College Hospitals, Middlesex Hospital, London. Source: Hyatt, P J Br-J-Hosp-Med. 1997 October 1-14; 58(7): 333-6 0007-1064
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Beneficial effects of atorvastatin in the treatment of hyperlipidemia after renal transplantation. Author(s): Klinische Abteilung fur Nephrologie und Dialyse, Universitatsklinik fur Innere Medizin III, Allgemeines Krankenhaus der Stadt Wien, Vienna, Austria. Source: Demetriou, D Shabpar, A Bohmig, G Schmaldienst, S Horl, W H Watschinger, B Wien-Klin-Wochenschr. 2000 April 21; 112(8): 358-61 0043-5325
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Bilateral pharmacokinetic interaction between cyclosporine A and atorvastatin in renal transplant recipients. Author(s): Medical Department, The National Hospital, Oslo, Norway.
[email protected] Source: Asberg, A Hartmann, A Fjeldsa, E Bergan, S Holdaas, H Am-J-Transplant. 2001 November; 1(4): 382-6 1600-6135
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By the way, doctor. My hair has been thinning out for the past decade or so, but since my doctor started me on Lipitor (atorvastatin) a few months ago for high cholesterol, I swear it's been falling out much faster. My doctor discounts the possibility, but I looked in the Physicians' desk reference (PDR) and alopecia is listed under “adverse reactions.” What do you think? Source: Lee, T H Harv-Health-Lett. 2000 July; 25(9): 8 1052-1577
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Cerivastatin and atorvastatin inhibit IL-3-dependent differentiation and IgEmediated histamine release in human basophils and downmodulate expression of the basophil-activation antigen CD203c/E-NPP3. Author(s): Department of Internal Medicine I, Division of Hematology & Hemostaseology, University of Vienna, Wahringer Gurtel 18-20, A-1090 Vienna, Austria. Source: Majlesi, Y Samorapoompichit, P Hauswirth, A W Schernthaner, G H Ghannadan, M Baghestanian, M Rezaie Majd, A Valenta, R Sperr, W R Buhring, H J Valent, P J-Leukoc-Biol. 2003 January; 73(1): 107-17 0741-5400
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Comparative efficacy study of atorvastatin vs simvastatin, pravastatin, lovastatin and placebo in type 2 diabetic patients with hypercholesterolaemia. Author(s): Department of Geriatrics and Metabolic Diseases, Second University of Naples, Italy.
[email protected] Source: Gentile, S Turco, S Guarino, G Sasso, C F Amodio, M Magliano, P Salvatore, T Corigliano, G Agrusta, M De Simone, G Gaeta, I Oliviero, B Torella, R Diabetes-ObesMetab. 2000 December; 2(6): 355-62 1462-8902
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Comparing the efficacy and safety of atorvastatin and simvastatin in Asians with elevated low-density lipoprotein-cholesterol--a multinational, multicenter, doubleblind study. Author(s): Department of Internal Medicine (Cardiology Section), National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei, Taiwan. Source: Wu, C C Sy, R Tanphaichitr, V Hin, A T Suyono, S Lee, Y T J-Formos-MedAssoc. 2002 July; 101(7): 478-87 0929-6646
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Comparison of atorvastatin alone versus simvastatin +/- cholestyramine in the management of severe primary hypercholesterolaemia (the six cities study). Author(s): Lipid Research Department, St Vincent's Hospital, Darlinghurst, NSW. Source: Simons, L A Aust-N-Z-J-Med. 1998 June; 28(3): 327-33 0004-8291
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Comparison of extended-release niacin and atorvastatin monotherapies and combination treatment of the atherogenic lipid profile in diabetes mellitus. Author(s): Diabetes Research Center, Tustin, California 92780, USA. Source: Van, Joanne T Pan, Jianqiu Wasty, Talat Chan, Eve Wu, Xiaoshan Charles, M Arthur Am-J-Cardiol. 2002 June 1; 89(11): 1306-8 0002-9149
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Comparison of the effects of atorvastatin or fenofibrate on nonlipid biochemical risk factors and the LDL particle size in subjects with combined hyperlipidemia. Author(s): Third Department of Internal Medicine, General University Hospital, Charles University, Prague, Czech Republic.
[email protected] Source: Melenovsky, V Malik, J Wichterle, D Simek, J Pisarikova, A Skrha, J Poledne, R Stavek, P Ceska, R Am-Heart-J. 2002 October; 144(4): E6 1097-6744
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Dose-dependent action of atorvastatin in type IIB hyperlipidemia: preferential and progressive reduction of atherogenic apoB-containing lipoprotein subclasses (VLDL2, IDL, small dense LDL) and stimulation of cellular cholesterol efflux. Author(s): Institut National de la Sante et de la Recherche Medicale (INSERM Unite 551), Hopital de la Pitie, Pavillon Benjamin Delessert, 83 Boulevard de l'Hopital, 75651 Paris, Cedex 13, France.
[email protected] Source: Guerin, M Egger, P Soudant, C Le Goff, W van Tol, A Dupuis, R Chapman, M J Atherosclerosis. 2002 August; 163(2): 287-96 0021-9150
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Dose-response effects of atorvastatin and simvastatin on high-density lipoprotein cholesterol in hypercholesterolaemic patients: a review of five comparative studies. Author(s): Department of Chemical Pathology, St. Thomas' Hospital, Lambeth Palace Road, SE1 7EH, London, UK. Source: Wierzbicki, A S Mikhailidis, D P Int-J-Cardiol. 2002 July; 84(1): 53-7 0167-5273
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Effect of atorvastatin (80 mg) initiated at the time of coronary artery stent implantation on C-reactive protein and six-month clinical events. Author(s): Cattedra di Cardiochirurgia, Universita Tor Vergata, Rome, Italy.
[email protected] Source: Gaspardone, A Versaci, F Proietti, I Tomai, F Altamura, L Skossyreva, O Chiariello, L Am-J-Cardiol. 2002 October 1; 90(7): 786-9 0002-9149
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Effects of atorvastatin (and blood pressure lowering comparing amlodipide-based therapy with beta-blocker-based therapy) on serum variables of cholesterol synthesis and absorption, thrombogenicity and on low-density lipoprotein oxidation in vivo. Author(s): Department of Medicine, Division of Cardiology, Helsinki University Hospital, Haartmaininkatu 4, 00290 Helsinki, Finland. Source: Nieminen, M S Viikari, J Ahotupa, M Vasankari, T Kantola, I Strandberg, T Vanhanen, H J-Hum-Hypertens. 2001 August; 15 Suppl 1: S27-9 0950-9240
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Effects of low doses of simvastatin and atorvastatin on high-density lipoprotein cholesterol levels in patients with hypercholesterolemia. Author(s): Department of Internal Medicine, University of Milan, Maggiore Hospital IRCCS, Italy.
[email protected] Source: Branchi, A Fiorenza, A M Torri, A Muzio, F Berra, C Colombo, E Dalla Valle, E Rovellini, A Sommariva, D Clin-Ther. 2001 June; 23(6): 851-7 0149-2918
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Effects of rosiglitazone alone and in combination with atorvastatin on the metabolic abnormalities in type 2 diabetes mellitus. Author(s): GlaxoSmithKline, Collegeville, Pennsylvania 19426, USA.
[email protected] Source: Freed, M I Ratner, R Marcovina, S M Kreider, M M Biswas, N Cohen, B R Brunzell, J D Am-J-Cardiol. 2002 November 1; 90(9): 947-52 0002-9149
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Effects of short-term atorvastatin treatment on global fibrinolytic capacity, and sLselectin and sFas levels in hyperlipidemic patients with coronary artery disease. Author(s): Department of Cardiology, Hacettepe University School of Medicine, Ankara, Turkey.
[email protected] Source: Atalar, E Ozmen, F Haznedaroglu, I Acil, T Ozer, N Ovunc, K Aksoyek, S Kes, S Int-J-Cardiol. 2002 August; 84(2-3): 227-31 0167-5273
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Efficacy and safety of atorvastatin 10 mg every other day in hypercholesterolemia. Author(s): Department of Medicine, Phramongkutklao College of Medicine, Bangkok, Thailand.
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Source: Piamsomboon, Chumpol Laothavorn, Prasart Saguanwong, Sopon Chatlaong, Boonsert Nasawadi, Chanarong Tanprasert, Pravit Pongsiri, Kittika J-Med-Assoc-Thai. 2002 March; 85(3): 297-300 0125-2208 •
Efficacy of atorvastatin compared with simvastatin in patients with hypercholesterolemia. Author(s): Point Medical, Dijon, France. Source: Farnier, M Portal, J J Maigret, P J-Cardiovasc-Pharmacol-Ther. 2000 January; 5(1): 27-32 1074-2484
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Efficacy of combination of atorvastatin and micronised fenofibrate in the treatment of severe mixed hyperlipidemia. Author(s): Department of Internal Medicine, Medical School, University of Ioannina, Greece.
[email protected] Source: Kiortisis, D N Millionis, H Bairaktari, E Elisaf, M S Eur-J-Clin-Pharmacol. 2000 December; 56(9-10): 631-5 0031-6970
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Factorial study of the effects of atorvastatin and fish oil on dyslipidaemia in visceral obesity. Author(s): Department of Medicine, University of Western Australia, Western Australian Institute for Medical Research, Royal Perth Hospital, Perth, Western Australia. Source: Chan, D C Watts, G F Mori, T A Barrett, P H Beilin, L J Redgrave, T G Eur-JClin-Invest. 2002 June; 32(6): 429-36 0014-2972
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High doses of atorvastatin and simvastatin induce key enzymes involved in VLDL production. Source: Roglans, N. Verd, J.C. Peris, C. Alegret, M. Vazquez, M. Adzet, T. Diaz, C. Hernandez, G. Laguna, J.C. Sanchez, R.M. Lipids. Champaign, Ill. : American Oil Chemists' Society, 1966-. May 2002. volume 37 (5) page 445-454. 0024-4201
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High-dose atorvastatin therapy in severe heterozygous familial hypercholesterolaemia. Author(s): Department of Chemical Pathology, St. Thomas's Hospital, London, UK. Source: Wierzbicki, A S Lumb, P J Semra, Y K Crook, M A QJM. 1998 April; 91(4): 291-4 1460-2725
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Implications of the atorvastatin versus revascularization treatment (AVERT) study for the clinician. Author(s): Foothill Cardiology/California Heart Care, 2601 West Alameda Avenue, Suite 304, Burbank, CA 91505, USA.
[email protected] Source: Eisenberg, D Curr-Cardiol-Repage 2000 September; 2(5): 433-8 1523-3782
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Increased atherosclerosis in diabetic dyslipidemic swine: protection by atorvastatin involves decreased VLDL triglycerides but minimal effects on the lipoprotein profile. Author(s): Dalton Cardiovascular Research Center, University of Missouri, Research Park, Columbia, MO, USA.
[email protected] Source: Dixon, J L Shen, S Vuchetich, J P Wysocka, E Sun, G Y Sturek, M J-Lipid-Res. 2002 October; 43(10): 1618-29 0022-2275
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Induction of lipoprotein lipase gene expression in 3T3-L1 preadipocytes by atorvastatin, a cholesterol- and triglyceride-lowering drug. Author(s): Biomedical Sciences, University of Missouri-Columbia, Mo 65211, USA. Source: Bey, L Maigret, P Laouenan, H Hamilton, M T Pharmacology. 2002 September; 66(1): 51-6 0031-7012
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Influence of atorvastatin versus simvastatin on fibrinogen and other hemorheological parameters in patients with severe hypercholesterolemia treated with regular lowdensity lipoprotein immunoadsorption apheresis. Author(s): Medical Department II, Klinikum Grosshadern, University of Munich, Germany.
[email protected] Source: Otto, C Geiss, H C Donner, M G Parhofer, K G Schwandt, P Ther-Apher. 2000 June; 4(3): 244-8 1091-6660
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Is a mechanical or a metabolic approach superior in the treatment of coronary disease? Results of the atorvastatin versus revascularization (AVERT) trial. Source: Waters, D Eur-Heart-J. 2000 July; 21(13): 1029-31 0195-668X
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Is alternate daily dose of atorvastatin effective in treating patients with hyperlipidemia? The Alternate Day Versus Daily Dosing of Atorvastatin Study (ADDAS). Author(s): Department of Pharmacy, Veterans Administration Central California Health Care System, Fresno, Calif 93703, USA. Source: Matalka, M S Ravnan, M C Deedwania, P C Am-Heart-J. 2002 October; 144(4): 674-7 1097-6744
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Lipitor (atorvastatin calcium) tablets. Source: Claussen, D W Gastroenterol-Nurs. 1998 Sep-October; 21(5): 219-20 1042-895X
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Long term efficacy and safety of atorvastatin in the treatment of severe type III and combined dyslipidaemia. Author(s): Department of Vascular Medicine, Academic Medical Centre, University of Amsterdam, 1105 AZ Amsterdam, Netherlands. Source: van Dam, M Zwart, M de Beer, F Smelt, A H Prins, M H Trip, M D Havekes, L M Lansberg, P J Kastelein, J J Heart. 2002 September; 88(3): 234-8 1468-201X
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Long-term (18-month) efficacy of atorvastatin therapy in type 2 diabetics at cardiovascular risk. Author(s): Diabetic Clinic, Casa di Cura Pineta del Carso, Viale Stazione 26, 34011 Aurisina, TS, Italy.
[email protected] Source: Velussi, M Nutr-Metab-Cardiovasc-Dis. 2002 February; 12(1): 29-35 0939-4753
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Metabolism and excretion of atorvastatin in rats and dogs. Author(s): Department of Pharmacokinetics, Dynamics, and Metabolism, Parke-Davis Pharmaceutical Research Co., Ann Arbor, Michigan 48105, USA. Source: Black, A E Hayes, R N Roth, B D Woo, P Woolf, T F Drug-Metab-Dispos. 1999 August; 27(8): 916-23 0090-9556
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Possible short-term amelioration of basilar plaque by high-dose atorvastatin: use of reductase inhibitors for intracranial plaque stabilization. Author(s): Stroke Service, Centennial Medical Center, 2400 Patterson Street, Suite 123, Nashville, TN 37203, USA. Source: Callahan, A S 3rd Berger, B L Beuter, M J Devlin, T G J-Neuroimaging. 2001 April; 11(2): 202-4 1051-2284
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Proapoptotic effect of atorvastatin on stimulated rabbit smooth muscle cells. Author(s): Institute of Pharmacological Sciences, University of Milan, Milan, Italy. Source: Baetta, R Donetti, E Comparato, C Calore, M Rossi, A Teruzzi, C Paoletti, R Fumagalli, R Soma, M R Pharmacol-Res. 1997 August; 36(2): 115-21 1043-6618
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Raman spectroscopic investigation of atorvastatin, amlodipine, and both on atherosclerotic plaque development in APOE*3 Leiden transgenic mice. Author(s): Department of Cardiology, C5-P, Leiden University Medical Center, P.O. Box 9600, 2300 RC, Leiden, The Netherlands. Source: van de Poll, S W Delsing, D J Jukema, J W Princen, H M Havekes, L M Puppels, G J van der Laarse, A Atherosclerosis. 2002 September; 164(1): 65-71 0021-9150
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Rhabdomyolysis associated with concomitant use of atorvastatin and cyclosporine. Author(s): College of Pharmacy and Allied Health Professions, St. John's University, Jamaica, NY 43210, USA. Source: Maltz, H C Balog, D L Cheigh, J S Ann-Pharmacother. 1999 November; 33(11): 1176-9 1060-0280
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Short term effect of atorvastatin and vitamin E on serum levels of C3, a sensitive marker of the risk of myocardial infarction in men. Author(s): Department of Internal Medicine, Cardioangiology, University of Bologna, Italy.
[email protected] Source: Muscari, A Bastagi, L Poggiopollini, G Tomassetti, V Massarelli, G Boni, P Puddu, P Cardiovasc-Drugs-Ther. 2001 September; 15(5): 453-8 0920-3206
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Short-term effects of atorvastatin on C-reactive protein. Author(s): Institute of Clinical Chemistry and Hematology, Kantonsspital, St. Gallen, Switzerland. Source: Riesen, W F Engler, H Risch, M Korte, W Noseda, G Eur-Heart-J. 2002 May; 23(10): 794-9 0195-668X
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Similar effects of atorvastatin, simvastatin and pravastatin on thrombogenic and inflammatory parameters in patients with hypercholesterolemia. Author(s): Department of Clinical Pharmacology, University of Vienna Medical School, Austria. Source: Joukhadar, C Klein, N Prinz, M Schrolnberger, C Vukovich, T Wolzt, M Schmetterer, L Dorner, G T Thromb-Haemost. 2001 January; 85(1): 47-51 0340-6245
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Simvastatin and atorvastatin enhance hypotensive effect of diltiazem in rats. Author(s): Department of Pharmacology, Hokkaido College of Pharmacy, 7-1 Katsuraoka, Otaru 047-0264, Japan. Source: Marumo, H Satoh, K Yamamoto, A Kaneta, S Ichihara, K Yakugaku-Zasshi. 2001 October; 121(10): 761-4 0031-6903
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The cost of reaching National Cholesterol Education Program (NCEP) goals in hypercholesterolaemic patients. A comparison of atorvastatin, simvastatin, lovastatin and fluvastatin. Author(s): Jacksonville Center for Clinical Research, Florida, USA. Source: Koren, M J Smith, D G Hunninghake, D B Davidson, M H McKenney, J M Weiss, S R Schrott, H G Henley, R W Tresh, P McLain, R W Bakker Arkema, R G Black, D M Pharmacoeconomics. 1998 July; 14(1): 59-70 1170-7690
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The effect of atorvastatin on postprandial lipaemia in overweight or obese women homozygous for apo E3. Author(s): Catholic University Leuven, University Hospital Gasthuisberg, Department of Endocrinology, Metabolism and Nutrition, Belgium.
[email protected] Source: Vansant, G Mertens, A Muls, E Acta-Cardiol. 2001 June; 56(3): 149-54 0001-5385
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The efficacy of atorvastatin in treating patients with hypercholesterolaemia to target LDL-cholesterol goals: the LIPI-GOAL trial. Author(s): Dienst Endocrinologie, Metabolisme en Voeding, Universitair Ziekenhuis Gasthuisberg, Leuven, Belgium.
[email protected] Source: Muls, E De Backer, G Brohet, C Heller, F Acta-Cardiol. 2001 April; 56(2): 109-14 0001-5385
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The HMG-CoA reductase inhibitor, atorvastatin, promotes a Th2 bias and reverses paralysis in central nervous system autoimmune disease. Author(s): Department of Neurology and Neurological Sciences, Beckman Center for Molecular Medicine, Stanford University, Stanford, California 94305, USA. Source: Youssef, S Stuve, O Patarroyo, J C Ruiz, P J Radosevich, J L Hur, E M Bravo, M Mitchell, D J Sobel, R A Steinman, L Zamvil, S S Nature. 2002 November 7; 420(6911): 78-84 0028-0836
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Treatment of heterozygous familial hypercholesterolemia: atorvastatin vs simvastatin. Author(s): Lipid Clinic, Department of Medical and Surgical Science, Section of Gerontology, University of Turin, Italy. Source: Bo, M Nicolello, M T Fiandra, U Mercadante, G Piliego, T Fabris, F Nutr-MetabCardiovasc-Dis. 2001 February; 11(1): 17-24 0939-4753
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Use of atorvastatin in hyperlipidemic hypertensive renal transplant recipients. Author(s): Department of Molecular Medicine, Karolinska Institutet, L3 Karolinska Hospital, 171 76 Stockholm, Sweden.
[email protected] Source: KrMarch, R T Ferraris, J R Ramirez, J A Sorroche, P Legal, S Cayssials, A PediatrNephrol. 2002 July; 17(7): 540-3 0931-041X
Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •
healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0
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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov
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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov
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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/
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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/
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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/
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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/
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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/
Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html
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Google: http://directory.google.com/Top/Health/Nutrition/
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Healthnotes: http://www.healthnotes.com/
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Open Directory Project: http://dmoz.org/Health/Nutrition/
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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/
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WebMDHealth: http://my.webmd.com/nutrition
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
The following is a specific Web list relating to atorvastatin; 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 Niacin Source: Integrative Medicine Communications; www.drkoop.com Vitamin a Source: Healthnotes, Inc.; www.healthnotes.com Vitamin B3 Source: Healthnotes, Inc.; www.healthnotes.com Vitamin B3 (niacin) Source: Integrative Medicine Communications; www.drkoop.com
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Minerals Atorvastatin Source: Healthnotes, Inc.; www.healthnotes.com Fluvastatin Source: Healthnotes, Inc.; www.healthnotes.com Hmg-coa Reductase Inhibitors (statins) Source: Integrative Medicine Communications; www.drkoop.com
Nutrition
Retinol Alternative names: Vitamin A (Retinol) Source: Integrative Medicine Communications; www.drkoop.com Simvastatin Source: Healthnotes, Inc.; www.healthnotes.com Vitamin a (retinol) Alternative names: Retinol Source: Integrative Medicine Communications; www.drkoop.com •
Food and Diet High Cholesterol Source: Healthnotes, Inc.; www.healthnotes.com
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CHAPTER 3. ATORVASTATIN
ALTERNATIVE
MEDICINE
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Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to atorvastatin. 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 atorvastatin 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 “atorvastatin” (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 atorvastatin: •
A new reality: achieving cholesterol-lowering goals in clinical practice. Author(s): Gaw A. Source: Atherosclerosis. Supplements. 2002 April; 2(4): 5-8; Discussion 8-11. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11976071&dopt=Abstract
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Atorvastatin and omega-3 fatty acids protect against activation of the coagulation system in patients with combined hyperlipemia. Author(s): Nordoy A, Svensson B, Hansen JB. Source: Journal of Thrombosis and Haemostasis : Jth. 2003 April; 1(4): 690-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12871402&dopt=Abstract
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Atorvastatin transport in the Caco-2 cell model: contributions of P-glycoprotein and the proton-monocarboxylic acid co-transporter. Author(s): Wu X, Whitfield LR, Stewart BH. Source: Pharmaceutical Research. 2000 February; 17(2): 209-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10751037&dopt=Abstract
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Effect of hydroxymethyl glutaryl coenzyme a reductase inhibitor therapy on high sensitive C-reactive protein levels. Author(s): Jialal I, Stein D, Balis D, Grundy SM, Adams-Huet B, Devaraj S. Source: Circulation. 2001 April 17; 103(15): 1933-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11306519&dopt=Abstract
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Effect of statin therapy on remnant lipoprotein cholesterol levels in patients with combined hyperlipidemia. Author(s): Stein DT, Devaraj S, Balis D, Adams-Huet B, Jialal I. Source: Arteriosclerosis, Thrombosis, and Vascular Biology. 2001 December; 21(12): 2026-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11742880&dopt=Abstract
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Effects of atorvastatin and omega-3 fatty acids on LDL subfractions and postprandial hyperlipemia in patients with combined hyperlipemia. Author(s): Nordoy A, Hansen JB, Brox J, Svensson B. Source: Nutr Metab Cardiovasc Dis. 2001 February; 11(1): 7-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11383326&dopt=Abstract
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Gateways to clinical trials. Author(s): Bayes M, Rabasseda X, Prous JR. Source: Methods Find Exp Clin Pharmacol. 2002 December; 24(10): 703-29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12616965&dopt=Abstract
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HMG-CoA reductase inhibitors reduce senescence and increase proliferation of endothelial progenitor cells via regulation of cell cycle regulatory genes. Author(s): Assmus B, Urbich C, Aicher A, Hofmann WK, Haendeler J, Rossig L, Spyridopoulos I, Zeiher AM, Dimmeler S. Source: Circulation Research. 2003 May 16; 92(9): 1049-55. Epub 2003 April 03. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12676819&dopt=Abstract
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Incremental reduction of serum total cholesterol and low-density lipoprotein cholesterol with the addition of plant stanol ester-containing spread to statin therapy. Author(s): Blair SN, Capuzzi DM, Gottlieb SO, Nguyen T, Morgan JM, Cater NB. Source: The American Journal of Cardiology. 2000 July 1; 86(1): 46-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10867091&dopt=Abstract
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Lopinavir/ritonavir: a review of its use in the management of HIV infection. Author(s): Cvetkovic RS, Goa KL. Source: Drugs. 2003; 63(8): 769-802. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12662125&dopt=Abstract
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Pharmacotherapy for dyslipidaemia - current therapies and future agents. Author(s): Bays H, Stein EA. Source: Expert Opinion on Pharmacotherapy. 2003 November; 4(11): 1901-38. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14596646&dopt=Abstract
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Serum noncholesterol sterols during inhibition of cholesterol synthesis by statins. Author(s): Miettinen TA, Gylling H, Lindbohm N, Miettinen TE, Rajaratnam RA, Relas H; Finnish Treat-to-Target Study Investigators. Source: The Journal of Laboratory and Clinical Medicine. 2003 February; 141(2): 131-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12577049&dopt=Abstract
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Statins and omega-3 fatty acids in the treatment of dyslipidemia and coronary heart disease. Author(s): Nordoy A. Source: Minerva Med. 2002 October; 93(5): 357-63. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12410168&dopt=Abstract
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The effects of three different LDL-apheresis methods on the plasma concentrations of E-selectin, VCAM-1, and ICAM-1. Author(s): Empen K, Otto C, Brodl UC, Parhofer KG. Source: Journal of Clinical Apheresis. 2002; 17(1): 38-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11948705&dopt=Abstract
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Usefulness of Orlistat in the treatment of severe hypertriglyceridemia. Author(s): Wierzbicki AS, Reynolds TM, Crook MA. Source: The American Journal of Cardiology. 2002 January 15; 89(2): 229-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11792350&dopt=Abstract
Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •
Alternative Medicine Foundation, Inc.: http://www.herbmed.org/
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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats
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Chinese Medicine: http://www.newcenturynutrition.com/
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drkoop.com: http://www.drkoop.com/InteractiveMedicine/IndexC.html
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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm
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Google: http://directory.google.com/Top/Health/Alternative/
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Healthnotes: http://www.healthnotes.com/
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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine
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Open Directory Project: http://dmoz.org/Health/Alternative/
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HealthGate: http://www.tnp.com/
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WebMDHealth: http://my.webmd.com/drugs_and_herbs
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/
The following is a specific Web list relating to atorvastatin; 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 High Cholesterol Source: Integrative Medicine Communications; www.drkoop.com Hypercholesterolemia Source: Integrative Medicine Communications; www.drkoop.com Insulin Resistance Syndrome Source: Healthnotes, Inc.; www.healthnotes.com
•
Herbs and Supplements Angkak Alternative names: Red Yeast Rice Source: Integrative Medicine Communications; www.drkoop.com Beni-koji Alternative names: Red Yeast Rice Source: Integrative Medicine Communications; www.drkoop.com Cholesterol-lowering Drugs Source: Healthnotes, Inc.; www.healthnotes.com Coenzyme Q10 Source: Healthnotes, Inc.; www.healthnotes.com Hong Qu Alternative names: Red Yeast Rice Source: Integrative Medicine Communications; www.drkoop.com
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Hung-chu Alternative names: Red Yeast Rice Source: Integrative Medicine Communications; www.drkoop.com Monascus Alternative names: Red Yeast Rice Source: Integrative Medicine Communications; www.drkoop.com Red Koji Alternative names: Red Yeast Rice Source: Integrative Medicine Communications; www.drkoop.com Red Leaven Alternative names: Red Yeast Rice Source: Integrative Medicine Communications; www.drkoop.com Red Rice Alternative names: Red Yeast Rice Source: Integrative Medicine Communications; www.drkoop.com Red Yeast Rice Alternative names: Angkak Source: Integrative Medicine Communications; www.drkoop.com Red Yeast Rice Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10054,00.html Zhitai Alternative names: Red Yeast Rice Source: Integrative Medicine Communications; www.drkoop.com Zue Zhi Kang Source: Integrative Medicine Communications; www.drkoop.com
General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.
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CHAPTER 4. CLINICAL TRIALS AND ATORVASTATIN Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning atorvastatin.
Recent Trials on Atorvastatin The following is a list of recent trials dedicated to atorvastatin.8 Further information on a trial is available at the Web site indicated. •
The inhibition of platelet antiaggregating activity of clopidogrel by atorvastatin detected by erythromycin breath test: a metabolic inhibition of hepatic cytochrome P450-3A Condition(s): Hypercholesterolemia; Thrombosis Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Research Resources (NCRR) Purpose - Excerpt: The objective of this study is to determine if the action of the drug called clopidogrel, that you will start taking, will be decreased by another drug called atorvastatin, that you will also start taking. Clopidogrel is an oral antiplatelet agent that has been shown to prevent strokes and heart attacks. Atorvastatin is a cholesterol lowering agent. Twenty adults 18-75 years of age requiring cholesterol-lowering agent and antiplatelet agent therapy will be recruited for this study during their cardiology clinic visitation. In one group, antiplatelet agent (clopidogrel) regimen will be administered first, then followed by cholesterol-lowering medication (atorvastatin). In the second group, atorvastatin will be administered first, followed by clopidogrel. A new test called the erythromycin breath test will be administered to you three times during the study to measure how your liver will metabolize these drugs. Blood samples will also be obtained to assess platelet function. The criteria for exclusion are patient refusal or inability to give written consent, patients with allergic reaction to erythromycin, patients with known bleeding problems, liver disease, significant lung
8
These are listed at www.ClinicalTrials.gov.
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disease kidney disease and pregnancy. Patients with psychiatric impairment and documented history of substance abuse will also be excluded from the study. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004564 •
Lipitor as a Treatment for Alzheimer's Disease Condition(s): Alzheimer Disease Study Status: This study is no longer recruiting patients. Sponsor(s): Institute for the Study of Aging; Pfizer Purpose - Excerpt: The purpose of this study is to assess the clinical benefit of Lipitor, a cholesterol-lowering drug, in the treatment of Alzheimer's disease. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00024531
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Pilot Study of Atorvastatin in Children with Chronic Hyperlipidemia Secondary to Nephrotic Syndrome Condition(s): Nephrotic Syndrome; Hyperlipidemia Study Status: This study is completed. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); Southwest Pediatric Nephrology Study Group Purpose - Excerpt: Objectives: I. Determine the effect of atorvastatin on the plasma levels of lipids, Lp(a), and apoproteins for treating hyperlipidemia in children with nephrotic syndrome in whom proteinuria and hyperlipidemia persist after other appropriate measures to treat their primary disease have been exhausted. II. Determine the safety and tolerability of atorvastatin in these patients. III. Provide preliminary data for a future investigation into the potential effect that lowering cholesterol levels may have on the rate of progression of renal insufficiency in such patients. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004466
Keeping Current on Clinical Trials The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately
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5,400 visitors daily. To access this database, simply go to the Web site at http://www.clinicaltrials.gov/ and search by “atorvastatin” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: •
For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/
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For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html
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For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/
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For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm
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For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm
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For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm
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For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp
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For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm
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For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/
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For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm
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For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm
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For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm
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For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm
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For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm
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For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials
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CHAPTER 5. PATENTS ON ATORVASTATIN Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.9 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “atorvastatin” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on atorvastatin, we have not necessarily excluded nonmedical patents in this bibliography.
Patents on Atorvastatin By performing a patent search focusing on atorvastatin, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. The following is an 9Adapted
from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.
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example of the type of information that you can expect to obtain from a patent search on atorvastatin: •
Atorvastatin hemi-calcium form VII Inventor(s): Aronhime; Judith (Rehovot, IL), Lidor-Hadas; Ramy (Kafar-Saba, IL), Lifshitz; Revital (Herzlia, IL), Niddam; Valerie (Even-Yeouda, IL) Assignee(s): Teva Pharmaceutical Industries Ltd. (Petah Tiqva, IL) Patent Number: 6,605,636 Date filed: November 5, 2001 Abstract: The present invention provides a novel form of atorvastatin hemi-calcium designated Form VII and novel processes for its preparation whereby another crystalline form of atorvastatin hemi-calcium is suspended in ethanol, preferably absolute ethanol, and is converted to the new form, which is then isolated. The present invention further provides a method of reducing the plasma low density lipoprotein level in patients suffering from or susceptible to hypercholesterolemia and compositions and dosage forms for practicing the invention. Excerpt(s): The present invention relates to crystalline polymorphic forms of atorvastatin hemi-calcium and novel processes for preparing crystalline solids. Atorvastatin is a member of the class of drugs called statins. Statin drugs are currently the most therapeutically effective drugs available for reducing low density lipoprotein (LDL) particle concentration in the blood stream of patients at risk for cardiovascular disease. A high level of LDL in the bloodstream has been linked to the formation of coronary lesions which obstruct the flow of blood and can rupture and promote thrombosis. Goodman and Gilman, The Pharmacological Basis of Therapeutics 879 (9th ed. 1996). Reducing plasma LDL levels has been shown to reduce the risk of clinical events in patients with cardiovascular disease and patients who are free of cardiovascular disease but who have hypercholesterolemia. Scandinavian Simvastatin Survival Study Group, 1994; Lipid Research Clinics Program, 1984a, 1984b. The mechanism of action of statin drugs has been elucidated in some detail. They interfere with the synthesis of cholesterol and other sterols in the liver by competitively inhibiting the 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase enzyme ("HMG-CoA reductase"). HMG-CoA reductase catalyzes the conversion HMG to mevalonate, which is the rate determining step in the biosynthesis of cholesterol, and so, its inhibition leads to a reduction in the concentration of cholesterol in the liver. Very low density lipoprotein (VLDL) is the biological vehicle for transporting cholesterol and triglycerides from the liver to peripheral cells. VLDL is catabolized in the peripheral cells which releases fatty acids which may be stored in adopcytes or oxidized by muscle. The VLDL is converted to intermediate density lipoprotein (IDL), which is either removed by an LDL receptor, or is converted to LDL. Decreased production of cholesterol leads to an increase in the number of LDL receptors and corresponding reduction in the production of LDL particles by metabolism of IDL. Web site: http://www.delphion.com/details?pn=US06605636__
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Hydrolysis of [R(R*,R*)]-2-(4-fluorophenyl)-.beta.,.delta.-dihydroxy-5-(1methylethyl)-3 -phenyl-4-[(phenylamino) carbonyl]-1H-pyrrole-1-heptanoic acid esters with calcium hydroxide Inventor(s): Ishai; Eti (Netanya, IL), Lidor-Hadas; Ramy (Kfar Saba, IL), Lifshitz; Revital (Herzlia, IL), Niddam; Valerie (Even-Yeouda, IL) Assignee(s): Teva Pharmaceutical Industries Ltd. (Petah Tiqva, IL) Patent Number: 6,528,661 Date filed: October 24, 2001 Abstract: The present invention provides a process for preparing atorvastatin hemicalcium from an atorvastatin ester derivative with calcium hydroxide. The process is conveniently incorporated into a process for preparing atorvastatin hemi-calcium from an acetonide protected, ester protected.beta.,.delta.-dihydroxy heptanoic acid precursor compound by a first acid hydrolysis step followed by base hydrolysis with calcium hydroxide. The latter process may be performed as a one-pot process. Excerpt(s): The present invention relates to compounds that suppress cholesterol biosynthesis in humans by competitively inhibiting 3-hydroxy-3-methyl-glutarylcoenzyme A reductase and, more particularly, to processes for preparing pharmaceutically appropriate salts for oral administration of such compounds. The '995 patent describes a preparation of atorvastatin hemi-calcium, which is the salt form of the drug that has been approved by the U.S. Food and Drug Administration for oral administration to human patients. To prepare atorvastatin hemi-calcium, the '995 patent teaches that the sodium salt is prepared first by dissolving the lactone in methanol and water and adding a little less than one equivalent of sodium hydroxide to the solution until the lactone has been opened as determined by high performance liquid chromatography (HPLC). The '995 patent then teaches that the hemi-calcium salt may be prepared from the sodium salt by treating it with one equivalent or a slight excess of calcium chloride dihydrate (CaCl.sub.2.2H.sub.2 O) (steps d and e of Scheme 3). To an atorvastatin sodium salt solution whose exact concentration has been determined by HPLC is slowly added an equivalent or slight excess of CaCl.sub.2.2H.sub.2 O at elevated temperature while agitating the solution. After completing the addition, atorvastatin hemi-calcium is obtained as a precipitate by cooling the solution. The '995 patent also describes how the pure R,R stereoisomer may be obtained from a mixture of R,R and S,S stereoisomers obtained from the '893 patent process. The convergent step of the process is a Paal Knorr reaction (step e). After the convergent step, the acetonide protecting group on the.beta. and.delta. hydroxyls is cleaved with acid (step f). The '627 patent teaches that the sodium salt may be prepared from the N,N-diphenyl amide without intermediate isolation of the lactone by treating it with sodium hydroxide in a mixture of methanol and water (step g). The hemi-calcium salt is then prepared by dissolving the sodium salt in a solution of calcium acetate (Ca(OAc).sub.2) at room temperature and crystallizing the hemi-calcium salt from the solution by cooling. The '627 patent also describes preparations in which other N,N-disubstituted acetamides are used in the first step in otherwise similar processes. The '627 process is said to be well adapted for large scale production of atorvastatin. Web site: http://www.delphion.com/details?pn=US06528661__
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Method and pharmaceutical composition for regulating lipid concentration Inventor(s): Bocan; Thomas M. A. (Ann Arbor, MI) Assignee(s): Warner-Lambert Company (Morris Plains, NJ) Patent Number: 6,093,719 Date filed: July 1, 1999 Abstract: The present invention is a combination of an ACAT inhibitor, for example, sulfamic acid, [[2,4,6-tris(1-methylethyl)phenyl]acetyl]-, 2,6-bis(1-methylethyl) phenyl ester, and an HMG-CoA-reductase inhibitor, for example, atorvastatin, effective for lipid regulation. The combination of agents results in a greater reduction in plasma VLDL and LDL cholesterol and increases HDL cholesterol than either alone resulting in a less atherogenic lipoportein profile. The combination is useful in the treatment of patients with or at risk of developing ischemic syndromes in order to restore endogenous vascular endothelium-dependent activities. Excerpt(s): The treatment of patients with or at risk of developing ischemic syndromes with doses of an HMG-CoA reductase inhibitor to lower total and LDL cholesterol is known. This is done in order to restore endogenous vascular endothelium-dependent activities including, but not limited to vasodilatory responses modulating vascular tone and blood flow, antiadherent properties of the blood vessel wall, and anticoagulation of platelets (International Publication Number WO 95/13063). There is evidence from animal models that compounds which inhibit the enzyme, acyl-coenzyme A:cholesterol acyltransferase (ACAT) will be effective anti-atherosclerotic agents, (Curr. Med. Chem., 1994;1:204-225). It is well-established that when the majority of cholesterol in plasma is carried on apolipoprotein B-containing lipoproteins, such as low-density lipoproteins (LDL-C) and very-low-density lipoproteins (VLDL-C), the risk of coronary artery disease in man is increased (Circulation, 1990;81:1721-1733). Conversely, high levels of cholesterol carried in high-density lipoproteins (HDL-C) is protective against coronary artery disease (Am. J. Med., 1977;62:707-714). Thus, a drug which reduces the levels of atherogenic LDL-C and VLDL-C and elevates levels of protective HDL-C will produce a less atherogenic lipoprotein profile and thus a beneficial effect on atherosclerotic disease and its complications. This beneficial effect was demonstrated in man in the Helsinki Heart Study with the lipid regulator gemfibrozil which decreased LDL-C, increased HDL-C, and reduced the incidence of coronary artery disease (N. Engl. J. Med., 1987;317:1237-1245). We have now shown that a combination of ACAT inhibitor and HMG-CoA reductase inhibitor when administered in a chow/fat diet results in a greater reduction in apo B-containing liproprotein than either alone and that a normalization of the plasma lipoprotein profile can be achieved. This means the combination treatment results in plasma lipoprotein profile associated with a decreased risk of coronary artery disease. Web site: http://www.delphion.com/details?pn=US06093719__
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Mutual prodrugs of amlodipine and atorvastatin Inventor(s): Chang; George (Ivoryton, CT), Hamanaka; Ernest S. (Gales Ferry, CT), LaMattina; John L. (Ledyard, CT) Assignee(s): Pfizer Inc (New York, NY) Patent Number: 6,486,182 Date filed: May 24, 2000
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Abstract: This invention relates to mutual prodrugs of amlodipine and atorvastatin and to pharmaceutical compositions thereof. This invention also relates to methods of treating angina pectoris, atherosclerosis, and hypertension and hyperlipidemia in a mammal using those prodrugs and compositions. This invention also relates to methods of managing cardiac risk in a mammal, including humans, presenting with symptoms of cardiac risk by administering those prodrugs and compositions. Excerpt(s): This invention relates to mutual prodrugs of amlodipine and atorvastatin, pharmaceutically acceptable acid addition salts thereof, pharmaceutical compositions thereof and methods of using such prodrugs and compositions to treat subjects suffering from angina pectoris, atherosclerosis, combined hypertension and hyperlipidemia and to treat subjects presenting with symptoms of cardiac risk, including humans. The conversion of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) to mevalonate is an early and rate-limiting step in the cholesterol biosynthetic pathway. This step is catalyzed by the enzyme HMG-CoA reductase. Statins inhibit HMG-CoA reductase from catalyzing this conversion. As such, statins are collectively potent lipid lowering agents. and is disclosed in U.S. Pat. No. 4,681,893, which is incorporated herein by reference. Web site: http://www.delphion.com/details?pn=US06486182__ •
Process for the preparation of amorphous atorvastatin calcium Inventor(s): Balazs; Laszlo (Budapest, HU), Barkoczy; Jozsef (Budapest, HU), Barta; Ferenc (Tiszavasvari, HU), Doman; Imre (Budapest, HU), Donath; Gyorgyi Vereczkeyne (Budapest, HU), Greff; Zoltan (Budapest, HU), Kirallyi; Zsuzsa Szent (Budapest, HU), Nagy; Kalman (Budapest, HU), Nagy; Peter Kotay (Vac, HU), Ratkai; Zoltan (Budapest, HU), Seres; Peter (Budapest, HU), Simig; Gyula (Budapest, HU) Assignee(s): Egis Gyogyszergyar Rt. (Budapest, HU) Patent Number: 6,646,133 Date filed: July 3, 2002 Abstract: The invention relates to a process for the preparation of amorphous atorvastatin calcium by recrystallization of crude atorvastatin from an organic solvent which comprises dissolving crude amorphous atorvastatin calcium in a lower alkanol containing 2-4 carbon atoms or a mixture of such alkanols under heating and isolating the amorphous atorvastatin calcium precipitated after cooling. The atorvastatin calcium obtained is a known valuable agent useful in treating hyperlipidemia and hypercholestrolemia. Excerpt(s): The invention relates to an improved new process for the preparation of atorvastatin calcium. The calcium salt of [R-(R.sup.x,R.sup. x)]-2-(4-fluorophenyl).beta.,.delta.-dihydroxy-5-[1-methyl-ethyl)-3-pheny l-4-[(phenylamino)-carbonyl]-1Hpyrrole-1-heptanoic acid having the INN atorvastatin is an inhibitor of the 3-hydroxy-3methylglutamine coenzyme A reductase enzyme. Due to this effect atorvastatin is a valuable lipide and cholesterol level decreasing agent and useful in treating hyperlipidemia and hypercholesterolemia. Atorvastatin was described the first time in U.S. Pat. No. 5,273,995. In this US patent specification there is no disclosure concerning the crystalline form of the product. The preparation of atorvastatin and key intermediates useful in the synthesis are described at several places in prior art (e.g. U.S. Pat. No. 5,003,080, U.S. Pat. No. 5,097,045, U.S. Pat. No. 5,103,024, U.S. Pat. No. 5,124,482, U.S. Pat. No. 5,149,837, U.S. Pat. No. 5,155,251, U.S. Pat. No. 5,216,174, U.S. Pat. No.
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5,245,047, U.S. Pat. No. 5,248,793, U.S. Pat. No. 5,280,126, U.S. Pat. No. 5,397,792 and U.S. Pat. No. 5,342,952). The preparation of atorvastatin calcium in a defined crystalline form is first described in WO 97/03958. Web site: http://www.delphion.com/details?pn=US06646133__ •
Process for the preparation of beta hydroxy-delta lactone using novel intermediates Inventor(s): Bhide; Sunil Ramchandra (Maharashtra, IN), Chavan; Subhash Prataprao (Maharashtra, IN), Ghorpade; Sandeep Raghunath (Maharashtra, IN), Kalkote; Uttam Ramrao (Maharashtra, IN), Ravindranathan; Thottappillil (Maharashtra, IN) Assignee(s): Council of Scientific & Industrial Research (New Delhi, IN) Patent Number: 6,417,374 Date filed: February 15, 2001 Abstract: The present invention relates to a process for the preparation of optically active 6-hydroxymethyl-4-(tert-butyldimethylsilyloxy)-(4R,6S)-tetrahydro-2H-2-pyr anone(.beta.-Hydroxy-.delta.-lactone) an important intermediate in the synthesis of biologically active drugs e.g. compactin, atorvastatin, fluvastatin, cholesterol lowering drugs. Excerpt(s): The compound.beta.-hydroxy-.delta.-lactone (1) is an important intermediate in the synthesis of biologically active drugs e.g. compactin, atorvastatin, fluvastatin, cholesterol lowering drugs. e) Racemic and optically active.beta.-hydroxy-.delta.-lactone from cis-cyclohexane-1,3,5-triol (K. Prasad & O. Repic, Tet. Lett., 1984, 25, 2435-38; H. Suemune, M. Takahashi, S. Maeda, Z. Fxi & K. Sakai, Tet. Asymm. 1990, 1, 425-8, M. Canda, V. Eyken & M. Vandewalle, Tet. Asymmetry 1990, 1, 17-20). 1. The processes use chemicals such as butyl lithium, lithium aluminum hydride, methoxy-diethylborane which are costly and difficult to handle and therefore make the process difficult. Web site: http://www.delphion.com/details?pn=US06417374__
•
Process for the production of amorphous [R-(R*,R*)]-2-(4-fluorophenyl)-.beta.,.delta.dihydroxy-5-(1-methylethy)-3-phenyl-4-[(phenylamino) carbonyl]-1H-pyrrole-1heptanoic acid calcium salt (2:1) Inventor(s): Lin; Min (Plainsboro, NJ), Schweiss; Dieter (Holland, MI) Assignee(s): Warner-Lambert Company (Morris Plains, NJ) Patent Number: 6,274,740 Date filed: September 7, 2000 Abstract: A novel process for the preparation of amorphous atorvastatin is described where crystalline Form I atorvastatin is dissolved in a non-hydroxylic solvent and after removal of the solvent affords amorphous atorvastatin. Excerpt(s): The present invention relates to a novel process for amorphous atorvastatin which is known by the chemical name [R--(R*,R*)]-2-(4-fluorophenyl)-.beta.,.delta.dihydroxy-5-(1-methylethyl) -3-phenyl-4-[(phenylamino) carbonyl]-1H-pyrrole-1heptanoic acid hemi calcium salt which is useful as a pharmaceutical agent. Atorvastatin is useful as an inhibitor of the enzyme 3-hydroxy-3-methylglutarylcoenzyme A reductase (HMG-COA reductase) and is thus useful as a hypolipidemic
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and hypocholesterolemic agent. U.S. Pat. No. 4,681,893, which is herein incorporated by reference, discloses certain trans-6-[2-(3- or 4-carboxamido-substituted-pyrrol-1yl)alkyl]-4-hydroxy-pyran-2-ones including trans (.+-.)-5- (4-fluorophenyl)-2-(1methylethyl)-N,4-diphenyl-1-[(2-tetrahydro-4-hydroxy -6-oxo-2H-pyran-2-yl)ethyl]-1Hpyrrole-3-carboxamide. U.S. Pat. No. 5,273,995, which is herein incorporated by reference, discloses the enantiomer having the R form of the ring-opened acid of trans-5(4-fluorophenyl)-2-(1-methylethyl)-N,4-diphenyl-1-[(2-tetrahydro-4 -hydroxy-6-oxo-2Hpyran-2-yl)ethyl]-1H-pyrrole-3-carboxamide, i.e., [R--(R*,R*)]-2-(4-fluorophenyl).beta.,.delta.-dihydroxy-5-(1-methylethyl) -3-phenyl-4-[(phenylamino)carbonyl]-1Hpyrrole-1-heptanoic acid. Web site: http://www.delphion.com/details?pn=US06274740__ •
Treatment of arteriosclerosis and xanthoma Inventor(s): Horikoshi; Hiroyoshi (Kobe, JP), Ito; Takashi (Kobe, JP), Tsujita; Yoshio (Tokyo, JP) Assignee(s): Sankyo Company, Limited (Tokyo, JP) Patent Number: 5,798,375 Date filed: July 2, 1996 Abstract: A combination of one or more HMG-CoA reductase inhibitors (for example pravastatin, lovastatin, simvastatin, fluvastatin, rivastatin or atorvastatin) with one or more insulin sensitizers (for example troglitazone, pioglitazone, englitazone, BRL-49653, 5-(4-{2-›1-(4-2'-pyridylphenyl)ethylideneaminooxy!-ethoxy}benzyl)thiazolid ine-2,4dione, 5-{4-(5-methoxy-3-methylimidazo›5,4-b!pyridin-2-yl-methoxy)benzyl}thiazoli dine-2,4-dione or its hydrochloride, 5-›4-(6-methoxy-l-methylbenzimidazol-2ylmethoxy)benzyl!thiazolidine-2,4-d ione, 5-›4-(l-methylbenzimidazol-2ylmethoxy)benzyl!-thiazolidine-2,4-dione and 5-›4-(5-hydroxy-1,4,6,7tetramethylbenzimidazol-2-ylmethoxy) benzyllthiazolidine-2,4-dione) exhibits a synergistic effect and is significantly better at preventing and/or treating arteriosclerosis and/or xanthoma than is either of the components of the combination alone. Excerpt(s): The present invention relates to methods and compositions for the treatment and prophylaxis of arteriosclerosis and/or xanthoma. Throughout the world, in recent years, the tendency has been for the incidence of coronary artery disease and arteriosclerosis, including atherosclerosis, to increase, even in those countries in which hitherto they have not been prevalent. Amongst the factors implicated in such an increase are changes in lifestyle, including the "Western" meat-rich diet, and the adoption of such a diet even in countries where it is not traditional, and the general increase in the average age of the population. As a result, these diseases and arteriosclerosis, in particular, are widely feared as arteriosclerosis is a well known potential cause of unexpected death, for example by such sequelae of arteriosclerosis as myocardial infarction. One of the main risk factors implicated in these diseases is a high blood plasma lipid level, particularly a high blood plasma cholesterol level. There have, therefore, been many attempts to use an agent which lowers the cholesterol level in order to prevent and cure these diseases, and many compounds have been developed which, to a greater or lesser extent, have this effect. For example, one such compound, which has been very successful and is very well known is pravastatin, which is a lipid regulating agent and is an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (hereinafter referred to as "HMG-CoA reductase inhibitor") which is believed to act on the rate-determining step of cholesterol biosynthesis. It has been reported that
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coronary arteriosclerosis and xanthoma may be prevented in rabbits receiving pravastatin, but its efficacy remains insufficient ›Biochimica et Biophysica Acta, 960, 294302 (1988)!. Studies to control coronary arteriosclerosis and xanthoma have been carried out using a combination of two lipid regulating agents, pravastatin and cholestyramine, which is well known as an agent for lowering lipoprotein levels, but the efficacy of this combination also remains insufficient ›Atherosclerosis, 83, 69-80 (1990)!. Web site: http://www.delphion.com/details?pn=US05798375__
Patent Applications on Atorvastatin As of December 2000, U.S. patent applications are open to public viewing.10 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to atorvastatin: •
Biomodulated multiparticulate formulations Inventor(s): Billotte, Anne; (San Diego, CA) Correspondence: PFIZER INC; 150 EAST 42ND STREET; 5TH FLOOR - STOP 49; NEW YORK; NY; 10017-5612; US Patent Application Number: 20030044459 Date filed: August 27, 2002 Excerpt(s): The present invention is concerned with means for adjusting the bioavailability of atorvastatin calcium by modulating its rate of release from multiparticulate formulations and with multiparticulate formulations, especially tablets and capsules, having said modulated rate of release. Atorvastatin calcium is a selective competitive inhibitor of HMG-CoA having potent lipid lowering activity which is useful as a hypolipidaemic and/or hypocholesterolaemic agent. It is the subject of European Patent No. 0409281 and is currently sold under the name `Lipitor.TM.`. European Patent No. 0680320 describes pharmaceutical compositions for the peroral treatment of hyperlipidaemia and hypercholesterolaemia which comprise atorvastatin calcium and at least one pharmaceutically acceptable metal salt additive designed to protect the active drug from any degrading or processing environment, as well as preserve it from photochemical decomposition during storage. A particularly preferred additive for this purpose is calcium carbonate. Such compositions typically comprise from 1% to 50% w/w of atorvastatin calcium and from 5% to 50% w/w of calcium carbonate and may be in the form of powders, tablets, dispersible granules, capsules, or cachets. There is no reference in the European patent to the pharmaceutically acceptable metal salt additives acting as biomodulators to alter the rate of release of atorvastatin calcium and therefore its bioavailability. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
10
This has been a common practice outside the United States prior to December 2000.
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Combination therapy Inventor(s): Scott, Robert Andrew Donald; (Riverside, CT) Correspondence: Gregg C. Benson; Pfizer Inc.; Patent Department, Box 519; Eastern Point Road; Groton; CT; 06340; US Patent Application Number: 20020099046 Date filed: October 23, 2001 Abstract: This invention relates to pharmaceutical combinations of atorvastatin or a pharmaceutically acceptable salt thereof and antihypertensive agents, kits containing such combinations and methods of using such combinations to treat subjects suffering from angina pectoris, atherosclerosis, combined hypertension and hyperlipidemia and to treat subjects presenting with symptoms of cardiac risk, including humans. This invention also relates to additive and synergistic combinations of atorvastatin or a pharmaceutically acceptable salt thereof and antihypertensive agents whereby those synergistic combinations are useful in treating subjects suffering from angina pectoris, atherosclerosis, combined hypertension and hyperlipidemia and those subjects presenting with symptoms of cardiac risk, including humans. Excerpt(s): The conversion of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) to mevalonate is an early and rate-limiting step in the cholesterol biosynthetic pathway. This step is catalyzed by the enzyme HMG-CoA reductase. Statins inhibit HMG-CoA reducatase from catalyzing this conversion. As such, statins are collectively potent lipid lowering agents. and is disclosed in U.S. Pat. No. 4,681,893, which is incorporated herein by reference. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Crystalline forms of atorvastatin Inventor(s): Blatter, Fritz; (Reinach, CH), Schoning, Kai-Uwe; (Windisch, CH), Szelagiewicz, Martin; (Munchenstein, CH), Van Der Schaaf, Paul Adriaan; (Allschwil, CH) Correspondence: CIBA SPECIALTY CHEMICALS CORPORATION; PATENT DEPARTMENT; 540 WHITE PLAINS RD; P O BOX 2005; TARRYTOWN; NY; 105919005; US Patent Application Number: 20030114686 Date filed: October 7, 2002 Abstract: The present invention is directed to new crystalline forms of Atorvastatin calcium (2:1), referred to hereinafter as polymorphic Forms X, A, B1, B2, C, D and E. Furthermore, the present invention is directed to processes for the preparation of these crystalline forms and pharmaceutical compositions comprising the crystalline forms. Excerpt(s): The present invention is directed to crystalline forms of Atorvastatin calcium, processes for their preparation and pharmaceutical compositions comprising these crystalline forms. Atorvastatin calcium is an orally-active hypocholesterolaemic, a liver-selective HMG-CoA reductase inhibitor. Processes for the preparation of Atorvastatin calcium are described in U.S. Pat. No. 5,298,627, U.S. Pat. No. 5,273,995 and WO-A-97/03960, and publications by P. L. Brower et al. in Tetrahedron Letters (1992), vol. 33, pages 2279-2282, K. L. Baumann et al. in Tetrahedron Letters (1992), vol. 33, pages 2283-2284 and A. Graul et al. in Drugs Future (1997), vol. 22, pages 956-968. This
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calcium salt (2:1) is desirable since it enables Atorvastatin calcium to be conveniently formulated. The processes in the above mentioned patents and publications result in the preparation of amorphous Atorvastatin calcium. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Factory scale process for producing crystalline atorvastatin trihydrate hemi calcium salt Inventor(s): Tully, William; (Midleton, IE) Correspondence: Francis J. Tinney; Warner-Lambert Company; 2800 Plymouth Road; Ann Arbor; MI; 48105; US Patent Application Number: 20020156294 Date filed: June 14, 2002 Abstract: A factory scale process for producing crystalline atorvastatine trihydrate hemi calcium salt includes the addition of extra methyl tert-butyl ether to the reaction mixture to supersaturate the crystallization matrix. A seed slurry is made up in a makeup/delivery vessel and delivered, under pressure, to the reaction mixture. The process produces crystalline atorvastatin calcium within a consistent size range on a factory scale. Excerpt(s): This application is related to and claims benefit of the following applications: International Application PCT/IE 00/00150 filed Dec. 18, 2000, which claims priority from International Application PCT/IE 99/00132 filed Dec. 17, 1999 all of which are incorporated herein by reference in their entirety. The invention relates to an improved process for producing crystalline atorvastatin calcium which is known by the chemical name [R-(R*,R*)]-2-(4-fluorophenyl)-.beta.,.delta.-dihydroxy-5-(1-methylethyl)-3phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid hemi calcium salt. Atorvastatin is useful as a selective and competitive inhibitor of the enzyme 3-hydroxy3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme that converts 3-hydroxy-3-methylglutaryl-coenzyme A to mevalonate, a precursor of sterols such as cholesterol. The conversion of HMG-CoA to mevalonate is an early and ratelimiting step in cholesterol biosynthesis. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Formulations of atorvastatin stabilized with alkali metal additions Inventor(s): Kumar, Pananchukunnath Manoj; (New Delhi, IN), Malik, Rajiv; (New Delhi, IN), Singh, Romi Barat; (Varanasi, IN) Correspondence: Jayadeep R. Deshmukh, Esq.; Ranbaxy Pharmaceuticals Inc.; Suite 2100; 600 College Road East; Princeton; NJ; 08540; US Patent Application Number: 20030175338 Date filed: February 14, 2003 Abstract: A pharmaceutical formulation having improved bioavailability and bioequivalence includes particles of amorphous and/or crystalline atorvastatin that have a particle size (d.sub.90) less than 150.mu.m and a mean particle size (d.sub.50) of the atorvastatin particles that is between approximately 5 and 50.mu.m. The atorvastatin can be one or more of atorvastatin calcium, atorvastatin magnesium,
Patents 109
atorvastatin aluminum, atorvastatin iron, and atorvastatin zinc. The formulations of atorvastatin can be stabilized by mixing atorvastatin with an alkali metal salt additive at between approximately 1.2% and less than 5% w/w of the formulation. The alkali metal salt additive may be one or more of sodium carbonate, sodium bicarbonate, sodium hydroxide, sodium silicate, disodium hydrogen orthophosphate, sodium dihydrogen phosphate, disodium hydrogen phosphate, sodium phosphate, sodium aluminate, calcium carbonate, calcium hydroxide, magnesium carbonate, magnesium hydroxide, magnesium silicate, magnesium aluminate, and aluminum magnesium hydroxide. The atorvastatin formulations can be used to treat medical conditions, including primary hypercholesterolemia, dysbetalipoproteinemia, and homozygous familial hypercholesterolemia. Excerpt(s): The technical field of the invention relates to stabilized atorvastatin, and more particularly to amorphous and crystalline atorvastatins and formulations stabilized with alkali metal salt additives and formulated with a small particle size of atorvastatin. Although cholesterol is an indispensable component of all cell membranes as well as a precursor of a variety of steroid hormones and bile acids, excessively high levels of blood cholesterol and lipids increase the risk of the onset of atherosclerosis and coronary heart disease. The blood cholesterol pool is generally dependent upon dietary uptake of cholesterol and the biosynthesis of cholesterol. HMG-CoA reductase enzyme inhibitors, such as atorvastatin, bring about a reduction in the levels of blood cholesterol, especially the low-density lipoproteins, by inhibiting the synthesis of cholesterol. They are therefore excellent candidates for controlling blood cholesterol levels. According to the U.S. Food and Drug Administration's (FDA) summary basis of approval (SBA) for Warner-Lambert's Lipitor.TM., atorvastatin is present in multiple amorphous and crystalline forms. Originally, atorvastatin was synthesized in the amorphous form and most of the clinical pharmacology studies were conducted on tablets prepared from this material. This form of atorvastatin was reported to be hygroscopic and unstable when exposed to oxygen. Later, a more stable crystalline form of atorvastatin was developed. Clinical studies on crystalline atorvastatin did not show any adverse implications over the amorphous form. Bioavailability studies on the tablets prepared using the crystalline form of atorvastatin, on the other hand, showed that the rate of atorvastatin absorption was significantly higher (i.e., an approximate 50% increase in C.sub.max) for these tablets than for tablets prepared by using the amorphous form of atorvastatin. The extent of atorvastatin absorption as determined from the area under the plasma concentration-time curve (AUC) was, however, the same for the two formulations. Due to its better stability and faster absorption from the gastrointestinal tract, crystalline atorvastatin is being used in the marketed formulation of atorvastatin. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Genetic test to determine non-responsiveness to statin drug treatment Inventor(s): Rotter, Jerome I.; (Los Angeles, CA), Scheuner, Maren T.; (Manhattan Beach, CA), Taylor, Kent D.; (Santa Paula, CA), Yang, Huiying; (Cerritos, CA) Correspondence: SIDLEY AUSTIN BROWN & WOOD; 555 West Fifth Street; Los Angeles; CA; 90013-1010; US Patent Application Number: 20020106657 Date filed: July 3, 2001
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Abstract: In a method for detecting a genetic predisposition in a human for nonresponsiveness to statin drug treatment for coronary artery disease, nucleic acids comprising nucleotide sequences of the human lipoprotein lipase (LPL) gene are amplified and analyzed. Homozygosity for a variant allele in a non-coding or untranslated region of the 3' end of LPL, for example, LPL HindIII 2/2 or (TTTA).sub.n 4/4 genotypes, is linked to non-responsiveness to treatment with statin drugs, including lovastatin, pravastatin, simvastatin, atorvastatin, fluvastatin, or cerivastatin. Oligonucleotide primer sequences, primer sets, and genetic testing kits allow the practitioner to practice the method and thus better individualize the treatment and improve the care of patients with coronary artery disease. Excerpt(s): Throughout this application various publications are referenced within parentheses. The disclosures of these publications in their entireties are hereby incorporated by reference in this application in order to more fully describe the state of the art to which this invention pertains. This invention relates to the medical arts. In particular, it relates to the field of genetic testing methods and diagnostic kits. Statin drugs--the most potent lipid-lowering agents currently available--are 3-hydroxy-3methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors. They include lovastatin, pravastatin, simvastatin, atorvastatin, fluvastatin, and cerivastatin. All these statin drugs share a common mechanism of action and have similar toxicity profiles. (E. von Kreutz and G. Schluter, Preclinical safety evaluation of cerivastatin, a novel HMG-CoA reductase inhibitor, Am. J. Cardiol. 82(4B):11J-17J [1998];A. G. Ollson [1998]). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Hydrolysis of [R (R*, R*)]-2-(4-fluorophenyl)-beta,delta-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid esters with calcium hydroxide Inventor(s): Ishai, Eti; (Netanya, IL), Lidor-Hadas, Ramy; (Kfar Saba, IL), Lifshitz, Revital; (Herzlia, IL), Niddam, Valerie; (Even-Yeouda, IL) Correspondence: KENYON & KENYON; ONE BROADWAY; NEW YORK; NY; 10004; US Patent Application Number: 20020099224 Date filed: October 24, 2001 Abstract: The present invention provides a process for preparing atorvastatin hemicalcium from an atorvastatin ester derivative with calcium hydroxide. The process is conveniently incorporated into a process for preparing atorvastatin hemi-calcium from an acetonide protected, ester protected.beta.,.delta.-dihydroxy heptanoic acid precursor compound by a first acid hydrolysis step followed by base hydrolysis with calcium hydroxide. The latter process may be performed as a one-pot process. Excerpt(s): This invention claims the benefit under 35 U.S.C. 1.119(e) of provisional applications Serial Nos. 60/249,319, filed Nov. 16, 2000; 60/312,144, filed Aug. 13, 2001 and provisional application Serial No. 60/326,529, filed Oct. 1, 2001, which are incorporated herein by reference. The present invention relates to compounds that suppress cholesterol biosynthesis in humans by competitively inhibiting 3-hydroxy-3methyl-glutaryl-coenzyme A reductase and, more particularly, to processes for preparing pharmaceutically appropriate salts for oral administration of such compounds. [R (R*, R*)]-2-(4-fluorophenyl)-.beta.,.delta.-dihydroxy-5-(1-methy- lethyl)3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid ("atorvastatin") is an
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inhibitor of cholesterol biosynthesis in humans. It is one of a class of drugs called statins. Statins suppress cholesterol biosynthesis by competitively inhibiting 3-hydroxy-3methyl-glutaryl-coenzyme A reductase ("HMG-CoA reductase"). HMG-CoA reductase catalyzes the conversion of HMG-CoA to mevalonate, which is the rate determining step in the biosynthesis of cholesterol. Goodman and Gilman, The Pharmacological Basis of Therapeutics 841 (MacMillan Publ. Co.: New York 7th ed. 1985). Decreased production of cholesterol stimulates LDL receptor activity and consequently reduces the concentration of LDL particles in the bloodstream. Reducing LDL concentration in the bloodstream decreases the risk of coronary artery disease J.A.M.A. 1984, 251, 351-74. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
METHODS AND COMPOSITIONS FOR ASSOCIATED WITH PULMONARY DISEASE
INHIBITING
INFLAMMATION
Inventor(s): HARLAN, JOHN M.; (SEATTLE, WA), LIU, LI; (REDMOND, WA), WINN, ROBERT K.; (BAINBRIDGE ISLAND, WA) Correspondence: CAMPBELL & FLORES LLP; 4370 LA JOLLA VILLAGE DRIVE; 7TH FLOOR; SAN DIEGO; CA; 92122; US Patent Application Number: 20010006656 Date filed: February 17, 1999 Abstract: The present invention provides an aerosol formulation of a 3-hydroxy-3methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitor. The HMG-CoA reductase inhibitor can be, for example, a statin such as lovastatin, pravastatin, simvastatin, cerivastatin, fluvastatin, atorvastatin or mevastatin. The invention also provides a method of treating a pulmonary disease with an aerosol formulation of a HMG-CoA reductase inhibitor. Excerpt(s): The present invention relates generally to the fields of medicine and molecular pathology and, more specifically, to methods of treating an inflammatory lung disease. A variety of pulmonary diseases are associated with inflammation, including acute and chronic diseases. Pulmonary diseases associated with inflammation include, for example, asthma, interstitial pneumonitis, emphysema, chronic bronchitis, adult respiratory distress syndrome (ARDS) and cystic fibrosis. Many of the lung diseases associated with inflammation have a significant impact on human health, quality of life and productivity. For example, approximately 5% of the United States population has signs or symptoms of asthma. Chronic obstructive pulmonary disease, including chronic bronchitis and emphysema, is the fourth leading cause of death in the United States. In addition, the United States has approximately 100,000 cases of adult respiratory distress syndrome (ARDS), which can follow systemic or pulmonary insults. Cystic fibrosis is the most common lethal genetic disease in Caucasians, affecting approximately one in 2,000 births among Americans of European descent. Therefore, inflammatory lung diseases have a major impact on human health. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Novel crystal forms of atorvastatin hemi-calcium and processes for their preparation as well as novel processes for preparing other forms Inventor(s): Aronhime, Judith; (Rehovot, IL), Ishai, Eti; (Netanya, IL), Lidor-Hadas, Ramy; (Kfar Saba, IL), Lifshitz, Revital; (Herzlia, IL), Niddam, Valerie; (Even-Yeouda, IL), Sambursky, Guy; (Hofit, IL) Correspondence: KENYON & KENYON; ONE BROADWAY; NEW YORK; NY; 10004; US Patent Application Number: 20020183378 Date filed: November 29, 2001 Abstract: The present invention provides novel forms of atorvastatin designated Forms VI, VIII, IX, X, XI and XII and novel processes for their preparation as well as processes for preparing atorvastatin Forms I, II, IV, V and amorphous atorvastatin. Excerpt(s): This application claims the benefit of provisional applications Serial Nos. 60/250,072, filed Nov. 30, 2000; 60/267,897, filed Feb. 9, 2001; 60/281,872, filed Apr. 5, 2001; 60/312,144, filed Aug. 13, 2001 and 60/326,529, filed Oct. 1, 2001, all of which are incorporated herein by reference. The present invention relates to crystalline polymorphic forms of atorvastatin hemi-calcium, novel processes for preparing crystalline forms of atorvastatin hemi-calcium and crystalline atorvastatin hemi-calcium with a small particle size distribution. Atorvastatin is a member of the class of drugs called statins. Statin drugs are currently the most therapeutically effective drugs available for reducing low density lipoprotein (LDL) particle concentration in the blood stream of patients at risk for cardiovascular disease. A high level of LDL in the bloodstream has been linked to the formation of coronary lesions which obstruct the flow of blood and can rupture and promote thrombosis. Goodman and Gilman, The Pharmacological Basis of Therapeutics 879 (9th ed. 1996). Reducing plasma LDL levels has been shown to reduce the risk of clinical events in patients with cardiovascular disease and patients who are free of cardiovascular disease but who have hypercholesterolemia. Scandinavian Simvastatin Survival Study Group, 1994; Lipid Research Clinics Program, 1984a, 1984b. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Pharmaceutical composition containing a combination of a statin and aspirin and method Inventor(s): Jain, Nemichand B.; (Cranbury, NJ), Ullah, Ismat; (Cranbury, NJ) Correspondence: Marla J. Mathias; Bristol-Myers Squibb Company; Patent Department; P.O. Box 4000; Princeton; NJ; 08543-4000; US Patent Application Number: 20020034546 Date filed: April 2, 2001 Abstract: A pharmaceutical composition is provided which is useful for cholesterol lowering and reducing the risk of a myocardial infarction, which includes a statin, such as pravastatin, lovastatin, simvastatin, atorvastatin, cerivastatin or fluvastatin, in combination with aspirin, in a manner to minimize interaction of aspirin with the statin and minimize side effects of aspirin. A method for lowering cholesterol and reducing risk of a myocardial infarction employing such composition is also provided.
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Excerpt(s): The present invention relates to a pharmaceutical composition which includes a statin cholesterol lowering agent and aspirin in a manner to minimize interaction of aspirin with the statin, for use in lowering cholesterol and reducing risk of a myocardial infarction, and to a method for lowering cholesterol and reducing risk of a myocardial infarction employing such composition. The use of aspirin for reducing the risk of a myocardial infarction and the use of statins for lowering cholesterol and preventing or treating atherosclerosis and cardiovascular disease and cerebrovascular disease are well documented. In fact, it is not uncommon that patients having elevated cholesterol levels who are at high risk for a myocardial infarction take both a statin and aspirin. However, use of both a statin and aspirin may require special care to insure that drug interaction, including physical and chemical incompatibility, and side effects, are kept to a minimum while achieving maximum benefit from these drugs. With regard to possible drug interaction, aspirin is an acid, while some of the statins, such as pravastatin, atorvastatin and cerivastatin, are alkali salts. Thus, mixing of such statins (alkali salts) with aspirin could result in aspirin hydrolysis as well as statin degradation. Pravastatin, on the other hand, is also a very acid labile compound. When pravastatin and aspirin are combined, the aspirin could cause pravastatin degradation which could result in lower bioavailability of pravastatin. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Pharmaceutical compositions of amlodipine and atorvastatin Inventor(s): Alani, Laman; (Ann Arbor, MI), Khan, Sadath U.; (Randolph, NJ), MacNeil, Thomas; (Ann Arbor, MI), Muhammad, Nouman A.; (Long Valley, NJ) Correspondence: Francis J. Tinney; Warner-Lambert Company; 2800 Plymouth Road; Ann Arbor; MI; 48105; US Patent Application Number: 20030114497 Date filed: July 25, 2002 Abstract: A pharmaceutical composition comprising two components:(a) one component comprising a granulation of atorvastatin or pharmaceutically acceptable salts thereof and a carrier including an alkalizing agent that forms a pH greater than 5; and(b) a second component comprising amlodipine or pharmaceutically acceptable salts thereof and a carrier excluding an alkalizing agent that forms a pH greater than 5, wherein the two components are combined to form a final composition for a solid dosage form is described as well as methods to prepare the compositions, kits for containing such compositions, and a method of treating angina pectoris, atherosclerosis, combined hypertension and hyperlipidemia and/or hypercholesterolemia, and symptoms of cardiac risk using a therapeutically effective amount of the pharmaceutical composition. Excerpt(s): This invention relates to pharmaceutical compositions comprising amlodipine and pharmaceutically acceptable salts thereof, and atorvastatin and pharmaceutically acceptable salts thereof, and a process for the preparation of the same, kits containing such compositions, as well as methods of using such compositions to treat subjects suffering from angina pectoris, atherosclerosis, combined hypertension and hyperlipidemia and/or hypercholesterolemia and to treat subjects presenting with symptoms of cardiac risk, including human subjects. The conversion of 3-hydroxy-3methylglutaryl-coenzyme A (HMG-CoA) to mevalonate is an early and rate-limiting step in the cholesterol biosynthetic pathway. This step is catalyzed by the enzyme HMG-CoA reductase. Statins inhibit HMG-CoA reductase from catalyzing this
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conversion. As such, statins are collectively potent lipid lowering agents. Atorvastatin and pharmaceutically acceptable salts thereof are selective, competitive inhibitors of HMG-CoA reductase. As such, atorvastatin calcium is a potent lipid lowering compound and is thus useful as a hypolipidemic and/or hypocholesterolemic agent. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Preparation of pharmaceutically acceptable atorvastatin salts in non-crystalline form Inventor(s): Sorsak, Gorazd; (Kidricevo, SI) Correspondence: HELLER EHRMAN WHITE & MCAULIFFE LLP; 275 MIDDLEFIELD ROAD; MENLO PARK; CA; 94025-3506; US Patent Application Number: 20030109569 Date filed: December 18, 2002 Abstract: Non-crystalline, in particular amorphous, pharmaceutically acceptable atorvastatin salts, especially the calcium salt, are prepared from atorvastatin lactone or from a compound of formula (I) 1where A denotes a common protecting group or separate protecting groups for the two hydroxy groups, and B denotes a carboxylic acid protecting group, without the need of prior formation of atorvastatin lactone, the crystalline form of the atorvastatin salt, or a mixture of amorphous and crystalline forms of the atorvastatin salt. Pharmaceutical formulations are prepared from these salts. Excerpt(s): This application is a continuation-in-part of International Application No. PCT/IB02/00161, filed Jan. 22, 2002 and designating the United States; which claims the priority of Slovenian Application No. P-01100010, filed Jan. 23, 2001. Each of these applications is incorporated into this application by reference. This invention relates to a method of preparing pharmaceutically acceptable atorvastatin salts in non-crystalline form. is known as an HMG-CoA reductase inhibitor and is used as an antihypercholesterolemic agent. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Process for the preparation of amorphous atorvastatin Inventor(s): Pflaum, Zlatko; (Domzale, SI) Correspondence: BROMBERG & SUNSTEIN LLP; 125 SUMMER STREET; BOSTON; MA; 02110-1618; US Patent Application Number: 20020183527 Date filed: June 6, 2002 Abstract: Atorvastatin, the substance known by the chemical name [R-(R*,R*)]-2-(4fluorophenyl)-.beta.,.delta.-dihydroxy-5-(1-methylethyl)-3-phenyl-4[(penylamino)carbonyl]-1H-pyrrole-1-heptanoic acid hemi calcium salt, is readily available in one of its crystalline forms as it is known from the prior art. The present invention relates to a novel process for preparing atorvastatin in an amorphous form by precipitating the atorvastatin using a solvent of a second type from a solution of atorvastatin which is provided with a solvent of a first type. This process is useful for the conversion of atorvastatin in a crystalline form into atorvastatin in an amorphous form.
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Excerpt(s): The present invention relates to a novel process for the preparation of atorvastatin in an amorphous form. Atorvastatin, the substance known by the chemical name [R-(R*,R*)]-2-(4-fluorophenyl)-.beta.,.delta.-dihydroxy-5-(1-methylethyl)-3phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid hemi calcium salt is known as HMG-CoA reductase inhibitor and is used as an antihypercholesterolemic agent. Processes for the preparation of atorvastatin and key intermediates are disclosed in the U.S. Pat. Nos. 5,003,080; 5,097,045; 5,103,024; 5,124,482; 5,149,837; 5,155,251; 5,216,174; 5,245,047; 5,248,793; 5,280,126; 5,342,952; and 5,397,792. Atorvastatin is usually prepared as its calcium salt since it enables atorvastatin to be conveniently formulated in the pharmaceutical formulations, for example, in tablets, capsules, powders and the like for oral administration. Atorvastatin can exist in an amorphous form or in one of the crystalline forms (Form I, Form II, Form III and Form IV), which are disclosed in the PCT patent applications WO-A-97/3958 and WO-A-97/3959. It is known that the amorphous forms in a number of pharmaceutical substances exhibit different dissolution characteristics and bioavailability patterns compared to the crystalline forms (Konno T., Chem Pharm Bull., 1990,38: 2003-2007). For some therapeutic indications the bioavailability is one of the key parameters determining the form of the substance to be used in a pharmaceutical formulation. Since processes for the crystallization and the preparation, respectively, of the amorphous substance are sometimes difficult to be performed, and as a product afford amorphous-crystalline mixtures, that is, a crystalline form instead of an amorphous form, there is a constant need for processes which enable the preparing of atorvastatin in an amorphous form without simultaneous formation of crystalline forms, or which will enable the conversion of the crystalline forms into the amorphous form. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Process for the production of amorphous atorvastatin calcium Inventor(s): Kumar, S. M. Dileep; (New Delhi, IN), Kumar, Yatendra; (Haryana, IN), Thaper, Rajesh Kumar; (Haryana, IN) Correspondence: JAYADEEP R. DESHMUKH, ESQ.; RANBAXY PHARMACEUTICALS INC.; SUITE 2100; 600 COLLEGE ROAD EAST; PRINCETON; NJ; 08540; US Patent Application Number: 20030149279 Date filed: March 3, 2003 Abstract: A process for the preparation of amorphous atorvastatin calcium and hydrates thereof which comprises: (a) dissolving crystalline atorvastatin calcium in a nonhydroxylic solvent; (b) adding a non-polar hydrocarbon anti-solvent or adding the dissolved atorvastatin to the non-polar anti-solvent to precipitate out atorvastatin calcium; and (c) removing the solvent by filtration to afford amorphous atorvastatin calcium. Excerpt(s): The present invention relates to a process for the production of amorphous atorvastatin calcium. Atorvastatin is chemically [R-(R*,R*)]-2-(4-fluoro-phenyl)-.beta. dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino) carbonyl]-1H pyrrole-1heptanoic acid. Atorvastatin calcium, a synthetic HMG-CoA reductase inhibitor, is used for the treatment of hyperlipidemia and hypercholesterolemia, both of which are risk factors for arteriosclerosis and coronary heart disease. Open dihydroxy carboxylic acid, lactone and various salt forms of atorvastatin have been synthesized. is more suited to formulations and has been recommended as a drug.
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Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Processes for desolvating solvates of atorvastatin hemi-calcium and atorvastatin hemi-calcium essentially free of organic solvent Inventor(s): Aronhime, Judith; (Rehovot, IL), Maidan-Hanoch, Dalia; (Kfar Yona, IL) Correspondence: KENYON & KENYON; ONE BROADWAY; NEW YORK; NY; 10004; US Patent Application Number: 20030216584 Date filed: February 19, 2003 Abstract: The present invention provides processes for removing organic solvent from crystals of atorvastatin hemi-calcium containing organic solvent. In one process, the organic solvent is displaced by vapor diffusion of water in a vessel maintained at elevated humidity. In a second process, the organic solvent is removed by fluidized bed drying. The present invention further provides atorvastatin hemi-calcium containing 1% or less organic solvent, which can be obtained from atorvastatin hemi-calcium that has been crystallized from an organic solvent-containing solution by practice of the processes of the invention. Excerpt(s): This application claims the benefit of U.S. provisional application No. 60/358,497, filed Feb. 19, 2002, which is incorporated by reference in its entirety. The present invention relates to atorvastatin hemi-calcium and, more particularly, to removal of organic solvent from atorvastatin hemi-calcium solvates and mixed solvates that are obtained from known procedures that use mixtures of organic solvent and, optionally, water in the production of atorvastatin hemi-calcium and particular crystalline forms thereof. Crystallization is a convenient, effective technique for purifying organic compounds. Purification by crystallization generally involves dissolving an impure substance in a solvent, removing insoluble impurities by filtering the solution and then precipitating the desired compound from the solution. Most soluble impurities are excluded from the growing crystals as the compound crystallizes. Ideally, soluble impurities remain in solution and are separated from the crystals by separating the solvent and washing the crystals. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Processes for preparing calcium salt forms of statins Inventor(s): Lidor-Hadas, Rami; (Kafar-Saba, IL), Lifshitz-Liron, Revital; (Herzlia, IL), Niddam-Hildesheim, Valerie; (Even-Yeouda, IL) Correspondence: KENYON & KENYON; ONE BROADWAY; NEW YORK; NY; 10004; US Patent Application Number: 20030114685 Date filed: August 16, 2002 Abstract: Processes for preparing a calcium salt of a statin from an ester derivative or protected ester derivative of the statin by using calcium hydroxide are provided. The ester or protected ester derivative is contacted with calcium hydroxide to obtain the calcium salt. Preferred statins are rosuvastatin, pitavastatin and atorvastatin, simvastatin and lovastatin. In processes beginning with a protected statin ester
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derivative, the protecting group is hydrolyzed during salt formation by contact with calcium hydroxide, or is contacted with an acid catalyst followed by contact with calcium hydroxide. Excerpt(s): This application claims the benefit of provisional application Serial No. 60/312,812, filed Aug. 16, 2001 and U.S. patent application Ser. No. 10/037,412, filed Oct. 24, 2001, which claims the benefit of provisional application Serial No. 60/249,319, filed Nov. 16, 2000, all of which are incorporated herein by reference. The present invention relates to processes for preparing calcium salt forms of statins. The class of drugs called statins are currently the most therapeutically effective drugs available for reducing low-density lipoprotein (LDL) particle concentration in the blood stream of patients at risk for cardiovascular disease and thus, statins are used in the treatment of hypercholesterolemia, hyperlipoproteinemia, and atherosclerosis. A high level of LDL in the bloodstream has been linked to the formation of coronary lesions that obstruct the flow of blood and can rupture and promote thrombosis. Goodman and Gilman, The Pharmacological Basis of Therapeutics, page 879 (9th Ed. 1996). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Stabilized pharmaceutically effective composition and pharmaceutical formulation comprising the same Inventor(s): Kerc, Janez; (Ljubljana, SI), Pflaum, Zlatko; (Domzale, SI) Correspondence: BROMBERG & SUNSTEIN LLP; 125 SUMMER STREET; BOSTON; MA; 02110-1618; US Patent Application Number: 20030109584 Date filed: November 15, 2002 Abstract: Lovastatin, pravastatin, simvastatin, mevastatin, atorvastatin, and derivatives and analogs thereof are known as HMG-CoA reductase inhibitors and are used as antihypercholesterolemic agents. The majority of them are produced by fermentation using microorganisms of different species identified as species belonging to Aspergillus, Monascus, Nocardia, Amycolatopsis, Mucor or Penicillium genus, and some are obtained by treating the fermentation products using the methods of chemical synthesis or they are the products of total chemical synthesis. The aforementioned active substances may be destabilized by the environmental factors, their degradation may also be accelerated by interactions with other pharmaceutical ingredients, such as fillers, binders, lubricants, glidants and disintegrating agents, therefore the pharmaceutical ingredients and the process for preparation of the pharmaceutical formulation should be meticulously chosen to avoid the aforementioned undesired interactions and reactions. The present invention relates to a HMG-CoA reductase inhibitor which is stabilized by forming a homogeneous composition with a buffering substance or a basifying substance. This homogeneous composition is suitably used as the active substance in a pharmaceutical formulation for the treatment of hypercholesterolemia and hyperlipidemia. Excerpt(s): This application is a continuation-in-part of U.S. application Ser. No. 09/591,322 filed on Jun. 9, 2000, which is currently pending. Its disclosure is incorporated herein by reference. The present invention relates to a newly stabilized HMG-CoA reductase inhibitor which is used in a pharmaceutical formulation being particularly suitable for the treatment of hypercholesterolemia and hyperlipidemia. More precisely, the present invention relates to a stabilized and very homogeneous
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composition mixture comprising a HMG-CoA reductase inhibitor, such as atorvastatin, pravastatin, fluvastatin and cerivastatin, or pharmaceutically active salts thereof, as well as solid pharmaceutical formulations containing the aforementioned homogeneous composition mixture as an active substance. The present invention relates more particularly to a stabilized and very homogeneous composition mixture comprising a HMG CoA reductase inhibitor or its pharmaceutically active salts, as well as solid pharmaceutical formulations containing the aforementioned homogeneous composition mixture as an active substance and which has increased stability as determined by a small change of its pH value and lactone content under storage and/or handling conditions. The present invention relates most particularly to a stabilized and very homogeneous composition mixture comprising pravastatin or its pharmaceutically active salts, as well as solid pharmaceutical formulations containing the aforementioned homogeneous composition mixture as an active substance and which has increased stability as determined by a small change of its pH value and lactone content under storage and/or handling conditions. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Sublingual use of inhibitors in the biosynthesis of cholesterol Inventor(s): Weiss, Sol; (Reseda, CA) Correspondence: MITCHELL, SILBERBERG & KNUPP, LLP; Trident Center; 11377 West Olympic Boulevard; Los Angeles; CA; 90064; US Patent Application Number: 20030100493 Date filed: June 4, 2002 Abstract: The present invention is a method introducing the sublingual placement of statin drugs whose names include: Fluvastatin, Atorvastatin, Lovastatin, Pravastatin and Simvastatin for heart related and other vascular emergencies. Current research challenges are developing many new derivatives and new classes of these HMG-CoA reductase inhibitors, which alter the biosynthesis of cholesterol. This method applies these medications (statin drugs) in a form such as sublingual (under the tongue) for rapid absorption and immediate high blood levels similar to that of nitroglycerin. The advantage of this method is that it will benefit those who are stricken with strokes and heart attacks by therefore saving lives and costs of medical care. Excerpt(s): This application contains subject matter of my provisional application Serial No. 60/306,977, filed Jul. 19, 2001, entitled Sublingual Use of Inhibitors in the Biosynthesis of Cholesterol, and in my provisional application Serial No. 60/314,532, filed Aug. 23, 2001, entitled Amendments to Serial No. 60/306,977. There is disclosed a method and combination of components to administer statin drugs in a beneficial method and manner. This method includes the sublingual administration of drugs selected from the class of drugs known as statin drugs. In addition to the method, there is disclosed a method and attendant components for administering sublingual medication or medications for emergency stabilization of ruptured plaques; suppression of thrombus or aggregation of platelets; alteration of inflammatory responses; improvement of endothelial function; reduction in cell death and augmentation of vasodilation. Disclosed is the combination of medications, such as a statin drug and nitroglycerin, and others, in sublingual administration. In addition, it has been found that combinations of other statin class drugs with other cholesterol lowering drugs such as niacin and other complications rupture, thrombus and platelet aggregation, inflammation, compromised endothelial function, vasoconstriction and cell death. These
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statin medications both by their own merits and in combinations with other drugs will lend to more beneficial and/or synergistic effects. Statins are like the new aspirins for use in the field of emergency medicine. The new Heart Protection Study (HPS) done in England reflects this latest and major breakthrough study of the statin class of drugs showing a reduction of adverse major vascular events over 5.5 years of treatment in high-risk patients. Most everyone is aware of the beneficial role of aspirin in emergency medicine. Furthering this theory of use ill medical emergencies are new reports of statins reducing infarct size in stroke patients. Statins favor endothelial nitric oxide synthase (eNOS) and block inducible nitric oxide synthase (iNOS) effects. These effects are neuroprotective by preserving blood flow and limiting neurological insult. Another ongoing study shows that a neurotoxin, Beta-Amyloid, derived from the Amyloid Precursor Protein (APP), was found embedded in the membranes of cells as disclosed in Alzheimer's disease, multiple sclerosis, vascular inflammations and other degenerative changes. Similar changes are recognized in patients with coronary artery and vascular diseases therefore implicating the plaque deposits occur elsewhere in the body as a result of the high cholesterol contents in tissues. High cholesterol induces these toxic changes. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Synergistic effects of amlodipine and atorvastatin metabolite as a basis for combination therapy Inventor(s): Mason, R. Preston; (Manchester, MA) Correspondence: PERKINS, SMITH & COHEN LLP; ONE BEACON STREET; 30TH FLOOR; BOSTON; MA; 02108; US Patent Application Number: 20020086889 Date filed: October 19, 2001 Abstract: The combination of amlodipine with atorvastatin metabolite shows a synergistic antioxidant effect on lipid peroxidation in human low-density lipoproteins and membrane vesicles enriched with polyunsaturated fatty acids. Inhibition of oxyradical damage by this drug combination was observed at therapeutic levels in a manner that could not be reproduced by the combination of amlodipine with other statins or the natural antioxidant, vitamin E. The basis for this potent activity is attributed to the chemical structures of these compounds and their molecular interactions with phospholipid molecules, as determined by x-ray diffraction analyses. This combination therapy can be used to treat cardiovascular disorders, especially coronary artery disease, by increasing the resistance of low-density lipoproteins and vascular cell membranes against oxidative modification. Excerpt(s): This application claims priority from the following four provisional patent applications: U.S. application No. 60/130,665, filed on Apr. 23, 1999; U.S. application No. 60/145,305, filed on Jul. 23, 1999; U.S. application No. 60/151,121, filed on Aug. 27, 1999; and U.S. application No. 60/166,592, filed on Nov. 19, 1999, and is a continuationin-part application of our U.S. application Ser. No. 09/556,930 filed Apr. 21, 2000. The present invention relates to pharmaceutical compositions and combinations to treat arterial and related heart disease and related ailments. Coronary artery disease (CAD) is the leading cause of mortality in the developed world, and is associated with substantial morbidity as well. Typically, the patient with CAD has several concomitant conditions, including hypertension, diabetes, and dyslipidemia, increasing overall risk for poor outcomes and complicating treatment.
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Therapeutic combination Inventor(s): Shear, Charles L.; (Gales Ferry, CT) Correspondence: Gregg C. Benson; Pfizer Inc.; Patent Department, MS 4159; Eastern Point Road; Groton; CT; 06340; US Patent Application Number: 20020035125 Date filed: August 14, 2001 Abstract: Pharmaceutical combinations of a CETP inhibitor and atorvastatin or hydroxy metabolites thereof or a pharmaceutically acceptable salt thereof, methods of using such combinations and kits containing such combinations for the treatment of atherosclerosis, angina, elevated cholesterol and low HDL levels and for the management of cardiac risk. Excerpt(s): This application claims priority from provisional application U.S. Ser No. 60/225,238 filed Aug. 15, 2000, the benefit of which is hereby claimed under 37 C.F.R.sctn.1.78(a)(3). This invention relates to pharmaceutical combinations of cholesterol ester transfer protein (CETP) inhibitors in particular, [2R,4S]4-[(3,5-bistrifluoromethyl-benzyl)-methoxycarbonyl-amino]-2-ethyl-6-trifluoromethyl-3,4dihydro-2H-quinoline-1-carboxylic acid ethyl ester, and atorvastatin and metabolites thereof and pharmaceutically acceptable salts thereof. [2R,4S]4-[(3,5-Bis-trifluoromethylbenzyl)-methoxycarbonyl-amino]-2- -ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline1-carboxylic acid ethyl ester is disclosed in PCT/IB99/01532 application published as WO 00/17164 on Mar. 30, 2000 as a CETP inhibitor for the elevation of certain plasma lipid levels and to lower certain other plasma lipid levels and accordingly to prevent the occurrence of and treat diseases such as lipid abnormalities, atherosclerosis and cardiovascular diseases. That published application also discloses the combination of a genus of 4-carboxyamino-2-substituted-1,2,3,4-tetrahydroquinolines with a preferred group of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors being lovastatin, simvastatin, pravastatin, fluvastatin, atorvastatin or rivastatin. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Tnf-alpha inhibitors Inventor(s): Funatsu, Masami; (Neyagawa-shi Osaka, JP), Ikeya, Kazuaki; (Ikoma-gun, Nara, JP), Naruo, Ken-ichi; (Sanda-shi, Hyogo, JP), Odaka, Hiroyuki; (Kobe-shi, Hyogo, JP), Sugiyama, Yasuo; (Kawanishi-shi, Hyogo, JP), Suzuki, Yoshiharu; (Suita-shi Osaka, JP) Correspondence: WENDEROTH, LIND & PONACK, L.L.P.; 2033 K STREET N. W.; SUITE 800; WASHINGTON; DC; 20006-1021; US Patent Application Number: 20030018040 Date filed: August 8, 2002 Abstract: There is provided a TNF-.alpha. inhibitor comprising at least one compound selected from cerivastatin, atorvastatin, simvastatin, pravastatin, itavastatin and (+)-(3R, 5S)-7-[4-(4-fluorophenyl)-6-isopropyl-2-(N-methyl-N-methanesulfonylamino) pyrimidin-5-yl]-3,5-dihydroxy-6 (E)-heptenoic acid, or a salt thereof, which is excellent
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in the preventing and treating effects to TNF-.alpha. -associated diseases such as inflammatory disease and has the sufficiently excellent nature as a medicine, such as absence of side effect. Excerpt(s): The present invention relates to a TNF-.alpha. inhibitor, useful as an agent for preventing or treating TNF-.alpha. -associated diseases, for example, inflammatory diseases, which contains at least one compound selected from cerivastatin, atorvastatin, simvastatin, pravastatin, itavastatin and (+)-(3R, 5S)-7-[4-(4-fluorophenyl) -6-isopropyl2-(N-methyl-N-methanesulfonylamino)pyrimidin-5-yl]-3,5-dihyd- roxy-6(E)-heptenoic acid, or a salt thereof. TNF (tumor necrosis factor)-.alpha. is thought to play an important role in various diseases. For example, in rheumatoid arthritis which is an inflammatory disease, it is thought that production of TNF-.alpha. is enhanced and this causes destruction of the joint tissue. Development of a TNF-.alpha. ( inhibitor is desired which is excellent in the effect of preventing and treating inflammatory diseases, and has the sufficiently excellent nature as a medicine such as absence of the side effect. 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 atorvastatin, 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 “atorvastatin” (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 atorvastatin. You can also use this procedure to view pending patent applications concerning atorvastatin. 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. PERIODICALS AND NEWS ON ATORVASTATIN Overview In this chapter, we suggest a number of news sources and present various periodicals that cover atorvastatin.
News Services and Press Releases One of the simplest ways of tracking press releases on atorvastatin 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 “atorvastatin” (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 atorvastatin. 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 “atorvastatin” (or synonyms). The following was recently listed in this archive for atorvastatin: •
Atorvastatin slightly clears existing artery plaque Source: Reuters Medical News Date: November 12, 2003
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Atorvastatin relieves claudication symptoms of peripheral artery disease Source: Reuters Medical News Date: September 01, 2003
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Effects of atorvastatin on clopidogrel similar to those of other statins Source: Reuters Industry Breifing Date: August 05, 2003
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FDA says counterfeit Lipitor contains active ingredient Source: Reuters Industry Breifing Date: June 17, 2003
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Atorvastatin monotherapy improves lipid profile in combined hyperlipidemia Source: Reuters Industry Breifing Date: April 21, 2003
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Pfizer's Lipitor may reduce MI, stroke in hypertensives with average cholesterol levels Source: Reuters Industry Breifing Date: April 02, 2003
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Atorvastatin may reduce MI and stroke in hypertensives with average cholesterol levels Source: Reuters Medical News Date: April 02, 2003
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Atorvastatin therapy may slow progression of chronic kidney disease Source: Reuters Industry Breifing Date: March 19, 2003
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Atorvastatin decreases hepatic lipase activity in diabetes Source: Reuters Industry Breifing Date: March 07, 2003
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Alternate day atorvastatin therapy effective, may cut costs Source: Reuters Industry Breifing Date: October 31, 2002
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Atorvastatin before or after coronary stenting reduces future ischemic event risk Source: Reuters Industry Breifing Date: October 29, 2002
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Atorvastatin reduces MI/stroke risk in hypertensive patients with low cholesterol Source: Reuters Industry Breifing Date: October 10, 2002
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Atorvastatin raises fibrinolytic activity in coronary artery disease Source: Reuters Industry Breifing Date: September 26, 2002
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Atorvastatin significantly reduces stroke rate in patients with acute coronary syndromes Source: Reuters Medical News Date: September 03, 2002
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Atorvastatin improves lipid profile but not endothelial function in type 2 diabetes Source: Reuters Industry Breifing Date: July 31, 2002
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AstraZeneca says Crestor helps more patients than Pfizer's Lipitor Source: Reuters Industry Breifing Date: July 09, 2002
Periodicals and News
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Atorvastatin lowers VEGF levels in coronary heart disease Source: Reuters Medical News Date: July 05, 2002
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Atorvastatin therapy significantly reduces C-reactive protein levels Source: Reuters Industry Breifing Date: June 21, 2002
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Atorvastatin does not improve vasoreactivity in type 2 diabetic patients Source: Reuters Industry Breifing Date: May 21, 2002
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Lipitor probe time extended Source: Reuters Industry Breifing Date: May 16, 2002
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CORRECTION: Pfizer cleared to recommend higher starting doses for Lipitor Source: Reuters Health eLine Date: May 02, 2002
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US FDA says lower starting dose of Lipitor OK Source: Reuters Health eLine Date: April 29, 2002
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Pfizer to recommend lower starting doses for Lipitor Source: Reuters Industry Breifing Date: April 29, 2002
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Lipitor fights MS symptoms in mice Source: Reuters Industry Breifing Date: April 22, 2002
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Atorvastatin counters MS symptoms in mice Source: Reuters Medical News Date: April 22, 2002
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Atorvastatin outperforms simvastatin in comparison trial Source: Reuters Industry Breifing Date: March 29, 2002
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Atorvastatin improves elasticity of small arteries and reduces blood pressure Source: Reuters Industry Breifing Date: December 25, 2001
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Pfizer expands Lipitor awareness efforts after Baycol recall Source: Reuters Industry Breifing Date: August 16, 2001
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High-dose atorvastatin improves cholesterol-related parameters of diabetes Source: Reuters Industry Breifing Date: August 08, 2001
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Atorvastatin reduces ischemic events after acute coronary episodes Source: Reuters Industry Breifing Date: April 03, 2001
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Rosuvastatin bests atorvastatin in two clinical trials Source: Reuters Medical News Date: January 12, 2001
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AstraZeneca's new statin Crestor beats Pfizer's Lipitor in study Source: Reuters Industry Breifing Date: January 12, 2001
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AstraZeneca headhunts Lipitor chief for statin battle Source: Reuters Industry Breifing Date: December 13, 2000
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Lipitor approves in Japan Source: Reuters Medical News Date: March 13, 2000
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Lipitor recommended for Japanese market approval Source: Reuters Medical News Date: January 21, 2000
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Warner-Lambert sues to end Lipitor pact; AHP prepared to revise value of deal Source: Reuters Medical News Date: December 01, 1999
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Warner-Lambert board to consider Lipitor pact this week Source: Reuters Medical News Date: November 23, 1999
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LDL target achieved with atorvastatin without dose titration Source: Reuters Medical News Date: November 01, 1999
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Grapefruit juice increases bioavailability of atorvastatin but not of pravastatin Source: Reuters Medical News Date: August 26, 1999
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Pfizer, Warner-Lambert extend atorvastatin marketing pact Source: Reuters Medical News Date: June 17, 1999
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Warner-Lambert expects Lipitor to top market Source: Reuters Medical News Date: April 26, 1999 The NIH
Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name.
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Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “atorvastatin” (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 “atorvastatin” (or synonyms). If you know the name of a company that is relevant to atorvastatin, 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 “atorvastatin” (or synonyms).
Academic Periodicals covering Atorvastatin Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to atorvastatin. In addition to these sources, you can search for articles covering atorvastatin that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”
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CHAPTER 7. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.
U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for atorvastatin. 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 atorvastatin. 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 atorvastatin: Atorvastatin •
Systemic - U.S. Brands: Lipitor http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203635.html
Hmg-Coa Reductase Inhibitors •
Systemic - U.S. Brands: Baycol; Lescol; Lipitor; Mevacor; Pravachol; Zocor http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202284.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
•
National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/
•
National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html
•
National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25
•
National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm
•
National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm
•
National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375
•
National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/
11
These publications are typically written by one or more of the various NIH Institutes.
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•
National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm
•
National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/
•
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm
•
National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm
•
National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/
•
National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/
•
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm
•
National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html
•
National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm
•
National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm
•
National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm
•
National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html
•
National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm
•
Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp
•
National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/
•
National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp
•
Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html
•
Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm
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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.12 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:13 •
Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html
•
HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html
•
NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html
•
Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/
•
Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html
•
Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html
•
Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/
•
Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html
•
Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html
•
Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html
•
MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html
12
Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 13 See http://www.nlm.nih.gov/databases/databases.html.
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•
Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html
•
Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html The Combined Health Information Database
A comprehensive source of information on clinical guidelines written for professionals is the Combined Health Information Database. You will need to limit your search to one of the following: Brochure/Pamphlet, Fact Sheet, or Information Package, and “atorvastatin” using the “Detailed Search” option. Go directly to the following hyperlink: 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 the publication date, select “All Years.” Select your preferred language and the format option “Fact Sheet.” Type “atorvastatin” (or synonyms) into the “For these words:” box. The following is a sample result: •
Aggressive Lipid Lowering Does Not Improve Endothelial Function in Type 2 Diabetes: The Diabetes Atorvastatin Lipid Intervention (DALI) Study: A Randomized, Double-Blind, Placebo-Controlled Trial Source: Diabetes Care. 25(7): 1211-1216. July 2002. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: Endothelial dysfunction is considered an important early marker of atherosclerosis (hardening of the arteries) and cardiovascular risk and is currently used as a surrogate end point for cardiovascular risk in clinical trials. Patients with type 2 diabetes show a characteristic dyslipidemia (abnormal blood fats, such as cholesterol). Aggressive lipid lowering might be an effective method to improve endothelial function in these patients. This article reports on a study of this hypothesis that featured 133 patients with type 2 diabetes without a history of cardiovascular disease. Patients were given atorvastatin (10 milligrams and 80 milligrams) during the study. Despite substantial lowering of all atherogenic lipid parameters, no improvement of endothelium-dependent vasodilation was found. The authors conclude that aggressive lipid lowering by administration of atorvastatin, resulting in substantial improvement of the lipid profile, did not reverse endothelial dysfunction. 1 figure. 2 tables. 42 references.
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. 14 15
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
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).
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Type “atorvastatin” (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 1045 0 891 11 0 1947
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 “atorvastatin” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
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
16
Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html.
17
The HSTAT URL is http://hstat.nlm.nih.gov/.
18
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. 19 Adapted from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html. 20
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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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/.
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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 atorvastatin 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 atorvastatin. 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 atorvastatin. 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 “atorvastatin”:
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•
Other guides Coronary Disease http://www.nlm.nih.gov/medlineplus/coronarydisease.html Drug and Medical Device Safety http://www.nlm.nih.gov/medlineplus/drugandmedicaldevicesafety.html Kidney Diseases http://www.nlm.nih.gov/medlineplus/kidneydiseases.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 atorvastatin. 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/
•
WebMDHealth: http://my.webmd.com/health_topics
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Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to atorvastatin. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with atorvastatin. 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 atorvastatin. 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 “atorvastatin” (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 “atorvastatin”. 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 “atorvastatin” (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 “atorvastatin” (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.
Finding Medical Libraries
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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
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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
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Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/
•
Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html
•
Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm
•
Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330
•
Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)
•
National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html
•
National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/
•
National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/
Finding Medical Libraries
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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
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Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html
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Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html
•
Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml
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Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp
•
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
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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/
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Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72
149
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).
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
151
ATORVASTATIN DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acetamides: Derivatives of acetamide that are used as solvents, as mild irritants, and in organic synthesis. [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] Acute leukemia: A rapidly progressing cancer of the blood-forming tissue (bone marrow). [NIH]
Acute renal: A condition in which the kidneys suddenly stop working. In most cases, kidneys can recover from almost complete loss of function. [NIH] Acyl: Chemical signal used by bacteria to communicate. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adipose Tissue: Connective tissue composed of fat cells lodged in the meshes of areolar tissue. [NIH] Adrenal Glands: Paired glands situated in the retroperitoneal tissues at the superior pole of each kidney. [NIH] Adrenal Medulla: The inner part of the adrenal gland; it synthesizes, stores and releases catecholamines. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adrenergic beta-Antagonists: Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic betaantagonists are used for treatment of hypertension, cardiac arrythmias, angina pectoris, glaucoma, migraine headaches, and anxiety. [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]
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
152 Atorvastatin
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] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]
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] 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] Allograft: An organ or tissue transplant between two humans. [NIH] Alopecia: Absence of hair from areas where it is normally present. [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] Ameliorated: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] 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]
Dictionary 153
Amputation: Surgery to remove part or all of a limb or appendage. [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] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] 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] Angiography: Radiography of blood vessels after injection of a contrast medium. [NIH] Angioscopy: Endoscopic examination, therapy or surgery performed on the interior of 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] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Anomalies: Birth defects; abnormalities. [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] 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]
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Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Antidote: A remedy for counteracting a poison. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antihypertensive: An agent that reduces high blood pressure. [EU] Antihypertensive Agents: Drugs used in the treatment of acute or chronic hypertension regardless of pharmacological mechanism. Among the antihypertensive agents are diuretics (especially diuretics, thiazide), adrenergic beta-antagonists, adrenergic alpha-antagonists, angiotensin-converting enzyme inhibitors, calcium channel blockers, ganglionic blockers, and vasodilator agents. [NIH] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] 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] Antipruritic: Relieving or preventing itching. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Antiviral Agents: Agents used in the prophylaxis or therapy of virus diseases. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly. [NIH] Anxiolytic: An anxiolytic or antianxiety agent. [EU] Aorta: The main trunk of the systemic arteries. [NIH] Aortic Valve: The valve between the left ventricle and the ascending aorta which prevents backflow into the left ventricle. [NIH] Apheresis: Components plateletpheresis. [NIH]
being
separated
out,
as
leukapheresis,
plasmapheresis,
Apolipoproteins: The protein components of lipoproteins which remain after the lipids to which the proteins are bound have been removed. They play an important role in lipid transport and metabolism. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to
Dictionary 155
mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Approximate: Approximal [EU] Aqueous: Having to do with water. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteriolosclerosis: Sclerosis and thickening of the walls of the smaller arteries (arterioles). Hyaline arteriolosclerosis, in which there is homogeneous pink hyaline thickening of the arteriolar walls, is associated with benign nephrosclerosis. Hyperplastic arteriolosclerosis, in which there is a concentric thickening with progressive narrowing of the lumina may be associated with malignant hypertension, nephrosclerosis, and scleroderma. [EU] Arteriosclerosis: Thickening and loss of elasticity of arterial walls. Atherosclerosis is the most common form of arteriosclerosis and involves lipid deposition and thickening of the intimal cell layers within arteries. Additional forms of arteriosclerosis involve calcification of the media of muscular arteries (Monkeberg medial calcific sclerosis) and thickening of the walls of small arteries or arterioles due to cell proliferation or hyaline deposition (arteriolosclerosis). [NIH] 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] Aspirin: A drug that reduces pain, fever, inflammation, and blood clotting. Aspirin belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is also being studied in cancer prevention. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Asymptomatic: Having no signs or symptoms of disease. [NIH] Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharnyx, larnyx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. [NIH] Atherogenic: Causing the formation of plaque in the lining of the arteries. [NIH] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Autodigestion: Autolysis; a condition found in disease of the stomach: the stomach wall is digested by the gastric juice. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autonomic: Self-controlling; functionally independent. [EU]
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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] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] 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 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] Bezafibrate: Antilipemic agent that lowers cholesterol and triglycerides. It decreases low density lipoproteins and increases high density lipoproteins. [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] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Biliary Tract: The gallbladder and its ducts. [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] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] Biological Transport: The movement of materials (including biochemical substances and drugs) across cell membranes and epithelial layers, usually by passive diffusion. [NIH]
Dictionary 157
Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biopterin: A natural product that has been considered as a growth factor for some insects. [NIH]
Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alteration may be either 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] Blasts: Immature blood cells. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Body Mass Index: One of the anthropometric measures of body mass; it has the highest correlation with skinfold thickness or body density. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone Marrow Cells: Cells contained in the bone marrow including fat cells, stromal cells, megakaryocytes, and the immediate precursors of most blood cells. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] 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]
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Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]
Breakdown: A physical, metal, or nervous collapse. [NIH] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Bronchitis: Inflammation (swelling and reddening) of the bronchi. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Buccal mucosa: The inner lining of the cheeks and lips. [NIH] Bullous: Pertaining to or characterized by bullae. [EU] Bypass: A surgical procedure in which the doctor creates a new pathway for the flow of body fluids. [NIH] Cadaver: A dead body, usually a human body. [NIH] Calcification: Deposits of calcium in the tissues of the breast. Calcification in the breast can be seen on a mammogram, but cannot be detected by touch. There are two types of breast calcification, macrocalcification and microcalcification. Macrocalcifications are large deposits and are usually not related to cancer. Microcalcifications are specks of calcium that may be found in an area of rapidly dividing cells. Many microcalcifications clustered together may be a sign of cancer. [NIH] Calcineurin: A calcium- and calmodulin-binding protein present in highest concentrations in the central nervous system. Calcineurin is composed of two subunits. A catalytic subunit, calcineurin A, and a regulatory subunit, calcineurin B, with molecular weights of about 60 kD and 19 kD, respectively. Calcineurin has been shown to dephosphorylate a number of phosphoproteins including histones, myosin light chain, and the regulatory subunit of cAMP-dependent protein kinase. It is involved in the regulation of signal transduction and is the target of an important class of immunophilin-immunosuppressive drug complexes in T-lymphocytes that act by inhibiting T-cell activation. EC 3.1.3.-. [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 Carbonate: Carbonic acid calcium salt (CaCO3). An odorless, tasteless powder or crystal that occurs in nature. It is used therapeutically as a phosphate buffer in hemodialysis patients and as a calcium supplement. [NIH] Calcium channel blocker: A drug used to relax the blood vessel and heart muscle, causing pressure inside blood vessels to drop. It also can regulate heart rhythm. [NIH] 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] Calcium Chloride: A salt used to replenish calcium levels, as an acid-producing diuretic, and as an antidote for magnesium poisoning. [NIH]
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Calcium Hydroxide: Ca(OH)2. A white powder that has many therapeutic uses. Because of its ability to stimulate mineralization, it is found in many dental formulations. [NIH] Calmodulin: A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels. [NIH] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carbohydrates: The largest class of organic compounds, including starches, glycogens, cellulose, gums, and simple sugars. Carbohydrates are composed of carbon, hydrogen, and oxygen in a ratio of Cn(H2O)n. [NIH] Carcinogenic: Producing carcinoma. [EU] Cardiac: Having to do with the heart. [NIH] Cardiology: The study of the heart, its physiology, and its functions. [NIH] Cardiorespiratory: Relating to the heart and lungs and their function. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Carotid Arteries: Either of the two principal arteries on both sides of the neck that supply blood to the head and neck; each divides into two branches, the internal carotid artery and the external carotid artery. [NIH] Catabolism: Any destructive metabolic process by which organisms convert substances into excreted compounds. [EU] Catalyse: To speed up a chemical reaction. [EU] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Catheters: A small, flexible tube that may be inserted into various parts of the body to inject or remove liquids. [NIH] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Cycle: The complex series of phenomena, occurring between the end of one cell division and the end of the next, by which cellular material is divided between daughter cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Division: The fission of a cell. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids,
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proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Centrifugation: A method of separating organelles or large molecules that relies upon differential sedimentation through a preformed density gradient under the influence of a gravitational field generated in a centrifuge. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] 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] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] Chemoprevention: The use of drugs, vitamins, or other agents to try to reduce the risk of, or delay the development or recurrence of, cancer. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Cholesterol Esters: Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a characteristic feature of atherosclerosis. [NIH] Cholestyramine: Strongly basic anion exchange resin whose main constituent is polystyrene trimethylbenzylammonium as Cl(-) anion. It exchanges chloride ions with bile salts, thus decreasing their concentration and that of cholesterol. It is used as a hypocholesteremic in diarrhea and biliary obstruction and as an antipruritic. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] 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] Chylomicrons: A class of lipoproteins that carry dietary cholesterol and triglycerides from the small intestines to the tissues. [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] Citrus: Any tree or shrub of the Rue family or the fruit of these plants. [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
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aminoacyl transfer-RNA and prevents peptide chain elongation. [NIH] Claudication: Limping or lameness. [EU] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]
Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [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] 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] Colestipol: Highly crosslinked and insoluble basic anion exchange resin used as anticholesteremic. It may also may reduce triglyceride levels. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] 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
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pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computerized axial tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography (CT scan), or computerized tomography. [NIH] Computerized tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized axial tomography (CAT) scan and computed tomography (CT scan). [NIH] Concomitant: Accompanying; accessory; joined with another. [EU] 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]
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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] Constriction: The act of constricting. [NIH] Constriction, Pathologic: The condition of an anatomical structure's being constricted beyond normal dimensions. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [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] Controlled clinical trial: A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]
Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] 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 Circulation: The circulation of blood through the coronary vessels of the heart. [NIH]
Coronary Disease: Disorder of cardiac function due to an imbalance between myocardial function and the capacity of the coronary vessels to supply sufficient flow for normal function. It is a form of myocardial ischemia (insufficient blood supply to the heart muscle) caused by a decreased capacity of the coronary vessels. [NIH] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Coronary Vessels: The veins and arteries of the heart. [NIH] Corpuscle: A small mass or body; a sensory nerve end bulb; a cell, especially that of the blood or the lymph. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] 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]
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Creatinine: A compound that is excreted from the body in urine. Creatinine levels are measured to monitor kidney function. [NIH] Cryptosporidiosis: Parasitic intestinal infection with severe diarrhea caused by a protozoan, Cryptosporidium. It occurs in both animals and humans. [NIH] Crystallization: The formation of crystals; conversion to a crystalline form. [EU] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cyclophosphamide: Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It is used in the treatment of lymphomas, leukemias, etc. Its side effect, alopecia, has been made use of in defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. [NIH] 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] Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Dairy Products: Raw and processed or manufactured milk and milk-derived products. These are usually from cows (bovine) but are also from goats, sheep, reindeer, and water buffalo. [NIH] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Delavirdine: A potent, non-nucleoside reverse transcriptase inhibitor with activity specific for HIV-1. [NIH]
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Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Depressive Disorder: An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent. [NIH] Dermatologist: A doctor who specializes in the diagnosis and treatment of skin problems. [NIH]
Dermatology: A medical specialty concerned with the skin, its structure, functions, diseases, and treatment. [NIH] Dermatosis: Any skin disease, especially one not characterized by inflammation. [EU] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Dialyzer: A part of the hemodialysis machine. (See hemodialysis under dialysis.) The dialyzer has two sections separated by a membrane. One section holds dialysate. The other holds the patient's blood. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Dietary Fats: Fats present in food, especially in animal products such as meat, meat products, butter, ghee. They are present in lower amounts in nuts, seeds, and avocados. [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] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Dihydroxy: AMPA/Kainate antagonist. [NIH] Dilatation: The act of dilating. [NIH] Dilatation, Pathologic: The condition of an anatomical structure's being dilated beyond normal dimensions. [NIH] Dilation: A process by which the pupil is temporarily enlarged with special eye drops (mydriatic); allows the eye care specialist to better view the inside of the eye. [NIH] 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] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention
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of subsidiary means. [EU] Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis. [NIH] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Disposition: A tendency either physical or mental toward certain diseases. [EU] Diuretic: A drug that increases the production of urine. [NIH] Diuretics, Thiazide: Diuretics characterized as analogs of 1,2,4-benzothiadiazine-1,1dioxide. All have a common mechanism of action and differ primarily in the dose required to produce a given effect. They act directly on the kidney to increase the excretion of sodium chloride and water and also increase excretion of potassium ions. [NIH] Dosage Forms: Completed forms of the pharmaceutical preparation in which prescribed doses of medication are included. They are designed to resist action by gastric fluids, prevent vomiting and nausea, reduce or alleviate the undesirable taste and smells associated with oral administration, achieve a high concentration of drug at target site, or produce a delayed or long-acting drug effect. They include capsules, liniments, ointments, pharmaceutical solutions, powders, tablets, etc. [NIH] Dose-dependent: Refers to the effects of treatment with a drug. If the effects change when the dose of the drug is changed, the effects are said to be dose dependent. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Resistance: Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from drug tolerance which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Duodenum: The first part of the small intestine. [NIH] Dyslipidemia: Disorders in the lipoprotein metabolism; classified as hypercholesterolemia, hypertriglyceridemia, combined hyperlipidemia, and low levels of high-density lipoprotein (HDL) cholesterol. All of the dyslipidemias can be primary or secondary. Both elevated levels of low-density lipoprotein (LDL) cholesterol and low levels of HDL cholesterol predispose to premature atherosclerosis. [NIH] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Elasticity: Resistance and recovery from distortion of shape. [NIH] Elastin: The protein that gives flexibility to tissues. [NIH]
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Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electrocoagulation: Electrosurgical procedures used to treat hemorrhage (e.g., bleeding ulcers) and to ablate tumors, mucosal lesions, and refractory arrhythmias. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Elementary Particles: Individual components of atoms, usually subatomic; subnuclear particles are usually detected only when the atomic nucleus decays and then only transiently, as most of them are unstable, often yielding pure energy without substance, i.e., radiation. [NIH] 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] Emergency Medicine: A branch of medicine concerned with an individual's resuscitation, transportation and care from the point of injury or beginning of illness through the hospital or other emergency treatment facility. [NIH] Emergency Treatment: First aid or other immediate intervention for accidents or medical conditions requiring immediate care and treatment before definitive medical and surgical management can be procured. [NIH] Emphysema: A pathological accumulation of air in tissues or organs. [NIH] Emulsions: Colloids of two immiscible liquids where either phase may be either fatty or aqueous; lipid-in-water emulsions are usually liquid, like milk or lotion and water-in-lipid emulsions tend to be creams. [NIH] Encephalitis: Inflammation of the brain due to infection, autoimmune processes, toxins, and other conditions. Viral infections (see encephalitis, viral) are a relatively frequent cause of this condition. [NIH] Encephalomyelitis: A general term indicating inflammation of the brain and spinal cord, often used to indicate an infectious process, but also applicable to a variety of autoimmune and toxic-metabolic conditions. There is significant overlap regarding the usage of this term and encephalitis in the literature. [NIH] Endocrine Glands: Ductless glands that secrete substances which are released directly into the circulation and which influence metabolism and other body functions. [NIH] Endopeptidases: A subclass of peptide hydrolases. They are classified primarily by their catalytic mechanism. Specificity is used only for identification of individual enzymes. They comprise the serine endopeptidases, EC 3.4.21; cysteine endopeptidases, EC 3.4.22; aspartic endopeptidases, EC 3.4.23, metalloendopeptidases, EC 3.4.24; and a group of enzymes yet to be assigned to any of the above sub-classes, EC 3.4.99. EC 3.4.-. [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, Lymphatic: Unbroken cellular lining (intima) of the lymph vessels (e.g., the high endothelial lymphatic venules). It is more permeable than vascular endothelium, lacking selective absorption and functioning mainly to remove plasma proteins that have filtered through the capillaries into the tissue spaces. [NIH] Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components from interstitium to lumen; this function has been most intensively studied in the blood capillaries. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxic: Of, relating to, or acting as an endotoxin (= a heat-stable toxin, associated with the outer membranes of certain gram-negative bacteria. Endotoxins are not secreted and are released only when the cells are disrupted). [EU] Endotoxin: Toxin from cell walls of bacteria. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]
Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. [NIH] Epidemiological: Relating to, or involving epidemiology. [EU] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Erythema: Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of causes. [NIH] Erythrocyte Membrane: The semipermeable outer portion of the red corpuscle. It is known as a 'ghost' after hemolysis. [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]
Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and
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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] Ether: One of a class of organic compounds in which any two organic radicals are attached directly to a single oxygen atom. [NIH] Ethnic Groups: A group of people with a common cultural heritage that sets them apart from others in a variety of social relationships. [NIH] Exfoliation: A falling off in scales or layers. [EU] 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] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [EU] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Farnesyl: Enzyme which adds 15 carbon atoms to the Ras precursor protein. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Femoral: Pertaining to the femur, or to the thigh. [EU] Femoral Artery: The main artery of the thigh, a continuation of the external iliac artery. [NIH] Femur: The longest and largest bone of the skeleton, it is situated between the hip and the knee. [NIH] Fermentation: An enzyme-induced chemical change in organic compounds that takes place in the absence of oxygen. The change usually results in the production of ethanol or lactic acid, and the production of energy. [NIH] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] Fibrinolytic: Pertaining to, characterized by, or causing the dissolution of fibrin by enzymatic action [EU] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Filtration: The passage of a liquid through a filter, accomplished by gravity, pressure, or vacuum (suction). [EU] Foam Cells: Lipid-laden macrophages originating from monocytes or from smooth muscle cells. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Fructose: A type of sugar found in many fruits and vegetables and in honey. Fructose is
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used to sweeten some diet foods. It is considered a nutritive sweetener because it has calories. [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] Ganglionic Blockers: Agents having as their major action the interruption of neural transmission at nicotinic receptors on postganglionic autonomic neurons. Because their actions are so broad, including blocking of sympathetic and parasympathetic systems, their therapeutic use has been largely supplanted by more specific drugs. They may still be used in the control of blood pressure in patients with acute dissecting aortic aneurysm and for the induction of hypotension in surgery. [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] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gemfibrozil: A lipid-regulating agent that lowers elevated serum lipids primarily by decreasing serum triglycerides with a variable reduction in total cholesterol. These decreases occur primarily in the VLDL fraction and less frequently in the LDL fraction. Gemfibrozil increases HDL subfractions HDL2 and HDL3 as well as apolipoproteins A-I and A-II. Its mechanism of action has not been definitely established. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]
Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genomics: The systematic study of the complete DNA sequences (genome) of organisms. [NIH]
Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]
Glomerular Filtration Rate: The volume of water filtered out of plasma through glomerular capillary walls into Bowman's capsules per unit of time. It is considered to be equivalent to inulin clearance. [NIH]
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Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [NIH] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [NIH] Glucuronic Acid: Derivatives of uronic acid found throughout the plant and animal kingdoms. They detoxify drugs and toxins by conjugating with them to form glucuronides in the liver which are more water-soluble metabolites that can be easily eliminated from the body. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [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] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Grafting: The operation of transfer of tissue from one site to another. [NIH] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [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] Haplotypes: The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the major histocompatibility complex. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart Transplantation: The transference of a heart from one human or animal to another. [NIH]
Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma
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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] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Heparin: Heparinic acid. A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. [NIH] Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatitis A: Hepatitis caused by hepatovirus. It can be transmitted through fecal contamination of food or water. [NIH] Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [NIH] Hepatovirus: A genus of Picornaviridae causing infectious hepatitis naturally in humans and experimentally in other primates. It is transmitted through fecal contamination of food or water. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] High-density lipoproteins: Lipoproteins that contain a small amount of cholesterol and carry cholesterol away from body cells and tissues to the liver for excretion from the body. Low-level HDL increases the risk of heart disease, so the higher the HDL level, the better. The HDL component normally contains 20 to 30 percent of total cholesterol, and HDL levels are inversely correlated with coronary heart disease risk. [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] 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] Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [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] 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,
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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] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hypercholesterolemia: Abnormally high levels of cholesterol in the blood. [NIH] Hyperlipidaemia: A general term for elevated concentrations of any or all of the lipids in the plasma, including hyperlipoproteinaemia, hypercholesterolaemia, etc. [EU] Hyperlipidemia: An excess of lipids in the blood. [NIH] Hyperlipoproteinemia: Metabolic disease characterized by elevated plasma cholesterol and/or triglyceride levels. The inherited form is attributed to a single gene mechanism. [NIH] Hyperplasia: An increase in the number of cells in a tissue or organ, not due to tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hypertriglyceridemia: Condition of elevated triglyceride concentration in the blood; an inherited form occurs in familial hyperlipoproteinemia IIb and hyperlipoproteinemia type IV. It has been linked to higher risk of heart disease and arteriosclerosis. [NIH] 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] Hypolipidemic: A drug that lowers abnormally high plasma concentrations of cholesterol or triglycerides or both. [NIH] Hypotensive: Characterized by or causing diminished tension or pressure, as abnormally low blood pressure. [EU] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Iliac Artery: Either of two large arteries originating from the abdominal aorta; they supply blood to the pelvis, abdominal wall and legs. [NIH] Immune function: Production and action of cells that fight disease or infection. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]
Immune system: The organs, cells, and molecules responsible for the recognition and
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disposal of foreign ("non-self") material which enters the body. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]
effects
of
foreign
Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunophilin: A drug for the treatment of Parkinson's disease. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] 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] Incision: A cut made in the body during surgery. [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infantile: Pertaining to an infant or to infancy. [EU] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]
Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Innervation: 1. The distribution or supply of nerves to a part. 2. The supply of nervous energy or of nerve stimulus sent to a part. [EU]
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Inorganic: Pertaining to substances not of organic origin. [EU] Insulator: Material covering the metal conductor of the lead. It is usually polyurethane or silicone. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Interindividual: Occurring between two or more individuals. [EU] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestines: The section of the alimentary canal from the stomach to the anus. It includes the large intestine and small intestine. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intravenous: IV. Into a vein. [NIH] Inulin: A starch found in the tubers and roots of many plants. Since it is hydrolyzable to fructose, it is classified as a fructosan. It has been used in physiologic investigation for determination of the rate of glomerular function. [NIH] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]
Involuntary: Reaction occurring without intention or volition. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Irritants: Drugs that act locally on cutaneous or mucosal surfaces to produce inflammation; those that cause redness due to hyperemia are rubefacients; those that raise blisters are vesicants and those that penetrate sebaceous glands and cause abscesses are pustulants; tear gases and mustard gases are also irritants. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU]
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Islet: Cell producing insulin in pancreas. [NIH] Isopropyl: A gene mutation inducer. [NIH] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Keto: It consists of 8 carbon atoms and within the endotoxins, it connects poysaccharide and lipid A. [NIH] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Kidney stone: A stone that develops from crystals that form in urine and build up on the inner surfaces of the kidney, in the renal pelvis, or in the ureters. [NIH] Kinetics: The study of rate dynamics in chemical or physical systems. [NIH] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] Lethal: Deadly, fatal. [EU] Leucine: An essential branched-chain amino acid important for hemoglobin formation. [NIH] Leukapheresis: The preparation of leukocyte concentrates with the return of red cells and leukocyte-poor plasma to the donor. [NIH] Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]
Ligaments: Shiny, flexible bands of fibrous tissue connecting together articular extremities of bones. They are pliant, tough, and inextensile. [NIH] Lipaemia: The presence of an excess of fats or lipids in the blood. [NIH] Lipase: An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and water to yield diacylglycerol and a fatty acid anion. It is produced by glands on the tongue and by the pancreas and initiates the digestion of dietary fats. (From Dorland, 27th ed) EC 3.1.1.3. [NIH] Lipid: Fat. [NIH] Lipid A: Lipid A is the biologically active component of lipopolysaccharides. It shows strong endotoxic activity and exhibits immunogenic properties. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an
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electron acceptor. [NIH] Lipodystrophy: A collection of rare conditions resulting from defective fat metabolism and characterized by atrophy of the subcutaneous fat. They include total, congenital or acquired, partial, abdominal infantile, and localized lipodystrophy. [NIH] Lipophilic: Having an affinity for fat; pertaining to or characterized by lipophilia. [EU] Lipopolysaccharides: Substance consisting of polysaccaride and lipid. [NIH] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Lipoprotein Lipase: An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and water to yield diacylglycerol and a fatty acid anion. The enzyme hydrolyzes triacylglycerols in chylomicrons, very-low-density lipoproteins, low-density lipoproteins, and diacylglycerols. It occurs on capillary endothelial surfaces, especially in mammary, muscle, and adipose tissue. Genetic deficiency of the enzyme causes familial hyperlipoproteinemia Type I. (Dorland, 27th ed) EC 3.1.1.34. [NIH] Lipoprotein(a): A family of lipoprotein particles varying in density and size depending on the protein-lipid ratio and the protein composition. These particles consist of apolipoprotein B-100 covalently linked to apolipoprotein-a by one or two disulfide bonds. There is a correlation between high plasma levels of this lipoprotein and increased risk for atherosclerotic cardiovascular disease. [NIH] 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] Localized: Cancer which has not metastasized yet. [NIH] Longitudinal Studies: Studies in which variables relating to an individual or group of individuals are assessed over a period of time. [NIH] Lovastatin: A fungal metabolite isolated from cultures of Aspergillus terreus. The compound is a potent anticholesteremic agent. It inhibits 3-hydroxy-3-methylglutaryl coenzyme A reductase (hydroxymethylglutaryl CoA reductases), which is the rate-limiting enzyme in cholesterol biosynthesis. It also stimulates the production of low-density lipoprotein receptors in the liver. [NIH] Low-density lipoprotein: Lipoprotein that contains most of the cholesterol in the blood. LDL carries cholesterol to the tissues of the body, including the arteries. A high level of LDL increases the risk of heart disease. LDL typically contains 60 to 70 percent of the total serum cholesterol and both are directly correlated with CHD risk. [NIH] Lubricants: Oily or slippery substances. [NIH] Lung metastases: Cancer that has spread from the original (primary) tumor to the lung. [NIH]
Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] Lupus Nephritis: Glomerulonephritis associated with systemic lupus erythematosus. It is classified into four histologic types: mesangial, focal, diffuse, and membranous. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries
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cells that help fight infection and disease. [NIH] Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Magnesium Hydroxide: Magnesium hydroxide (Mg(OH)2). An inorganic compound that occurs in nature as the mineral brucite. It acts as an antacid with cathartic effects. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Magnetic Resonance Spectroscopy: Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (magnetic resonance imaging). [NIH] 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] Major Histocompatibility Complex: The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) transplantation antigens, genes which control the structure of the immune responseassociated (Ia) antigens, the immune response (Ir) genes which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Mammary: Pertaining to the mamma, or breast. [EU] Mammogram: An x-ray of the breast. [NIH] Manic: Affected with mania. [EU] Meat: The edible portions of any animal used for food including domestic mammals (the major ones being cattle, swine, and sheep) along with poultry, fish, shellfish, and game. [NIH]
Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger
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cells which do not exist in mammals. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Melanosomes: Melanin-containing organelles found in melanocytes and melanophores. [NIH]
Membrane: A very thin layer of tissue that covers a surface. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Menopause: Permanent cessation of menstruation. [NIH] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] 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 and may cause blindness. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microcalcifications: Tiny deposits of calcium in the breast that cannot be felt but can be detected on a mammogram. A cluster of these very small specks of calcium may indicate that cancer is present. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Microsomal: Of or pertaining to microsomes : vesicular fragments of endoplasmic reticulum formed after disruption and centrifugation of cells. [EU] 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]
Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Mineralization: The action of mineralizing; the state of being mineralized. [EU] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH]
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Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monocyte: A type of white blood cell. [NIH] Mononuclear: A cell with one nucleus. [NIH] Monotherapy: A therapy which uses only one drug. [EU] Morphological: Relating to the configuration or the structure of live organs. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Mucosa: A mucous membrane, or tunica mucosa. [EU] Multicenter study: A clinical trial that is carried out at more than one medical institution. [NIH]
Multidrug resistance: Adaptation of tumor cells to anticancer drugs in ways that make the drugs less effective. [NIH] Multiple sclerosis: A disorder of the central nervous system marked by weakness, numbness, a loss of muscle coordination, and problems with vision, speech, and bladder control. Multiple sclerosis is thought to be an autoimmune disease in which the body's immune system destroys myelin. Myelin is a substance that contains both protein and fat (lipid) and serves as a nerve insulator and helps in the transmission of nerve signals. [NIH] Myelin: The fatty substance that covers and protects nerves. [NIH] Myelodysplasia: Abnormal bone marrow cells that may lead to myelogenous leukemia. [NIH]
Myelogenous: Produced by, or originating in, the bone marrow. [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] Myopathy: Any disease of a muscle. [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 muscles. [NIH]
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Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Necrolysis: Separation or exfoliation of tissue due to necrosis. [EU] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Nelfinavir: A potent HIV protease inhibitor. It is used in combination with other antiviral drugs in the treatment of HIV in both adults and children. [NIH] Neopterin: A pteridine derivative present in body fluids; elevated levels result from immune system activation, malignant disease, allograft rejection, and viral infections. (From Stedman, 26th ed) Neopterin also serves as a precursor in the biosynthesis of biopterin. [NIH] Nephritis: Inflammation of the kidney; a focal or diffuse proliferative or destructive process which may involve the glomerulus, tubule, or interstitial renal tissue. [EU] Nephrology: A subspecialty of internal medicine concerned with the anatomy, physiology, and pathology of the kidney. [NIH] Nephropathy: Disease of the kidneys. [EU] Nephrosis: Descriptive histopathologic term for renal disease without an inflammatory component. [NIH] Nephrotic: Pertaining to, resembling, or caused by nephrosis. [EU] Nephrotic Syndrome: Clinical association of heavy proteinuria, hypoalbuminemia, and generalized edema. [NIH] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] 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] Neurotoxicity: The tendency of some treatments to cause damage to the nervous system. [NIH]
Neurotoxin: A substance that is poisonous to nerve tissue. [NIH] Niacin: Water-soluble vitamin of the B complex occurring in various animal and plant
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tissues. Required by the body for the formation of coenzymes NAD and NADP. Has pellagra-curative, vasodilating, and antilipemic properties. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]
Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Nitroglycerin: A highly volatile organic nitrate that acts as a dilator of arterial and venous smooth muscle and is used in the treatment of angina. It provides relief through improvement of the balance between myocardial oxygen supply and demand. Although total coronary blood flow is not increased, there is redistribution of blood flow in the heart when partial occlusion of coronary circulation is effected. [NIH] Non-nucleoside: A member of a class of compounds, including delavirdine, loviride and nevirapine, that acts to directly combine with and block the action of HIV's reverse transcriptase. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nutritional Status: State of the body in relation to the consumption and utilization of nutrients. [NIH] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Omega-3 fatty acid: A type of fat obtained in the diet and involved in immunity. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Ophthalmoplegia: Paralysis of one or more of the ocular muscles due to disorders of the eye muscles, neuromuscular junction, supporting soft tissue, tendons, or innervation to the muscles. [NIH] Organ Culture: The growth in aseptic culture of plant organs such as roots or shoots, beginning with organ primordia or segments and maintaining the characteristics of the organ. [NIH] Organelles: Specific particles of membrane-bound organized living substances present in
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eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Overweight: An excess of body weight but not necessarily body fat; a body mass index of 25 to 29.9 kg/m2. [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] Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatitis: Acute or chronic inflammation of the pancreas, which may be asymptomatic or symptomatic, and which is due to autodigestion of a pancreatic tissue by its own enzymes. It is caused most often by alcoholism or biliary tract disease; less commonly it may be associated with hyperlipaemia, hyperparathyroidism, abdominal trauma (accidental or operative injury), vasculitis, or uraemia. [EU] Paralysis: Loss of ability to move all or part of the body. [NIH] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH] Partial response: A decrease in the size of a tumor, or in the extent of cancer in the body, in response to treatment. [NIH] Particle: A tiny mass of material. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]
Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH]
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Peptide Chain Elongation: The process whereby an amino acid is joined through a substituted amide linkage to a chain of peptides. [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] Perioperative: Around the time of surgery; usually lasts from the time of going into the hospital or doctor's office for surgery until the time the patient goes home. [NIH] Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral Vascular Disease: Disease in the large blood vessels of the arms, legs, and feet. People who have had diabetes for a long time may get this because major blood vessels in their arms, legs, and feet are blocked and these limbs do not receive enough blood. The signs of PVD are aching pains in the arms, legs, and feet (especially when walking) and foot sores that heal slowly. Although people with diabetes cannot always avoid PVD, doctors say they have a better chance of avoiding it if they take good care of their feet, do not smoke, and keep both their blood pressure and diabetes under good control. [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of Winslow, or epiploic foramen. [NIH] Peritoneal Dialysis: Dialysis fluid being introduced into and removed from the peritoneal cavity as either a continuous or an intermittent procedure. [NIH] Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering the inside of the abdominal wall and the visceral peritoneum covering the bowel, the mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal layer of the bowel wall. [NIH] Peroral: Performed through or administered through the mouth. [EU] 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 Solutions: Homogeneous liquid preparations that contain one or more chemical substances dissolved, i.e., molecularly dispersed, in a suitable solvent or mixture of mutually miscible solvents. For reasons of their ingredients, method of preparation, or use, they do not fall into another group of products. [NIH] Pharmacodynamic: Is concerned with the response of living tissues to chemical stimuli, that is, the action of drugs on the living organism in the absence of disease. [NIH] 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] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenyl: Ingredient used in cold and flu remedies. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine
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(sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylated: Attached to a phosphate group. [NIH] Photocoagulation: Using a special strong beam of light (laser) to seal off bleeding blood vessels such as in the eye. The laser can also burn away blood vessels that should not have grown in the eye. This is the main treatment for diabetic retinopathy. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]
Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasmapheresis: Procedure whereby plasma is separated and extracted from anticoagulated whole blood and the red cells retransfused to the donor. Plasmapheresis is also employed for therapeutic use. [NIH] Plasmin: A product of the lysis of plasminogen (profibrinolysin) by plasminogen activators. It is composed of two polypeptide chains, light (B) and heavy (A), with a molecular weight of 75,000. It is the major proteolytic enzyme involved in blood clot retraction or the lysis of fibrin and quickly inactivated by antiplasmins. EC 3.4.21.7. [NIH] Plasminogen: Precursor of fibrinolysin (plasmin). It is a single-chain beta-globulin of molecular weight 80-90,000 found mostly in association with fibrinogen in plasma; plasminogen activators change it to fibrinolysin. It is used in wound debriding and has been investigated as a thrombolytic agent. [NIH] Plasminogen Activators: A heterogeneous group of proteolytic enzymes that convert plasminogen to plasmin. They are concentrated in the lysosomes of most cells and in the vascular endothelium, particularly in the vessels of the microcirculation. EC 3.4.21.-. [NIH] Platelet 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]
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Plateletpheresis: The preparation of platelet concentrates with the return of red cells and platelet-poor plasma to the donor. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Pneumonitis: A disease caused by inhaling a wide variety of substances such as dusts and molds. Also called "farmer's disease". [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Polyunsaturated fat: An unsaturated fat found in greatest amounts in foods derived from plants, including safflower, sunflower, corn, and soybean oils. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postoperative: After surgery. [NIH] Postoperative Period: The period following a surgical operation. [NIH] Postprandial: Occurring after dinner, or after a meal; postcibal. [EU] Post-translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Pravastatin: An antilipemic fungal metabolite isolated from cultures of Nocardia autotrophica. It acts as a competitive inhibitor of HMG CoA reductase (hydroxymethylglutaryl CoA reductases). [NIH] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU]
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Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Prednisolone: A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states. [NIH] Prednisone: A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver. [NIH] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Primary endpoint: The main result that is measured at the end of a study to see if a given treatment worked (e.g., the number of deaths or the difference in survival between the treatment group and the control group). What the primary endpoint will be is decided before the study begins. [NIH] Primary Prevention: Prevention of disease or mental disorders in susceptible individuals or populations through promotion of health, including mental health, and specific protection, as in immunization, as distinguished from the prevention of complications or after-effects of existing disease. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Prodrug: A substance that gives rise to a pharmacologically active metabolite, although not itself active (i. e. an inactive precursor). [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Prophylaxis: An attempt to prevent disease. [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] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protease Inhibitors: Compounds which inhibit or antagonize biosynthesis or actions of proteases (endopeptidases). [NIH] Protein 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
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thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not working properly. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]
Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] 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]
Purifying: Respiratory equipment whose function is to remove contaminants from otherwise wholesome air. [NIH] Pyridoxal: 3-Hydroxy-5-(hydroxymethyl)-2-methyl-4- pyridinecarboxaldehyde. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons,
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alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radioactive: Giving off radiation. [NIH] Ramipril: A long-acting angiotensin-converting enzyme inhibitor. It is a prodrug that is transformed in the liver to its active metabolite ramiprilat. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Randomized clinical trial: A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial. [NIH] 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] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Red Nucleus: A pinkish-yellow portion of the midbrain situated in the rostral mesencephalic tegmentum. It receives a large projection from the contralateral half of the cerebellum via the superior cerebellar peduncle and a projection from the ipsilateral motor cortex. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Refractory: Not readily yielding to treatment. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Resolving: The ability of the eye or of a lens to make small objects that are close together, separately visible; thus revealing the structure of an object. [NIH] Respiratory distress syndrome: A lung disease that occurs primarily in premature infants; the newborn must struggle for each breath and blueing of its skin reflects the baby's inability to get enough oxygen. [NIH] Resuscitation: The restoration to life or consciousness of one apparently dead; it includes such measures as artificial respiration and cardiac massage. [EU] Retinoids: Derivatives of vitamin A. Used clinically in the treatment of severe cystic acne, psoriasis, and other disorders of keratinization. Their possible use in the prophylaxis and treatment of cancer is being actively explored. [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] Rhabdomyolysis: Necrosis or disintegration of skeletal muscle often followed by
190 Atorvastatin
myoglobinuria. [NIH] Rheology: The study of the deformation and flow of matter, usually liquids or fluids, and of the plastic flow of solids. The concept covers consistency, dilatancy, liquefaction, resistance to flow, shearing, thixotrophy, and viscosity. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Risk patient: Patient who is at risk, because of his/her behaviour or because of the type of person he/she is. [EU] Ritonavir: An HIV protease inhibitor that works by interfering with the reproductive cycle of HIV. [NIH] Rosiglitazone: A drug taken to help reduce the amount of sugar in the blood. Rosiglitazone helps make insulin more effective and improves regulation of blood sugar. It belongs to the family of drugs called thiazolidinediones. [NIH] Salicylate: Non-steroidal anti-inflammatory drugs. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [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] Saquinavir: An HIV protease inhibitor which acts as an analog of an HIV protease cleavage site. It is a highly specific inhibitor of HIV-1 and HIV-2 proteases. [NIH] Saturated fat: A type of fat found in greatest amounts in foods from animals, such as fatty cuts of meat, poultry with the skin, whole-milk dairy products, lard, and in some vegetable oils, including coconut, palm kernel, and palm oils. Saturated fat raises blood cholesterol more than anything else eaten. On a Step I Diet, no more than 8 to 10 percent of total calories should come from saturated fat, and in the Step II Diet, less than 7 percent of the day's total calories should come from saturated fat. [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] Scleroderma: A chronic disorder marked by hardening and thickening of the skin.
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Scleroderma can be localized or it can affect the entire body (systemic). [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Sedative: 1. Allaying activity and excitement. 2. An agent that allays excitement. [EU] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Senescence: The bodily and mental state associated with advancing age. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serous: Having to do with serum, the clear liquid part of blood. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Simvastatin: A derivative of lovastatin and potent competitive inhibitor of 3-hydroxy-3methylglutaryl coenzyme A reductase (hydroxymethylglutaryl CoA reductases), which is the rate-limiting enzyme in cholesterol biosynthesis. It may also interfere with steroid hormone production. Due to the induction of hepatic LDL receptors, it increases breakdown of LDL-cholesterol (lipoproteins, LDL cholesterol). [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]
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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] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Sodium Bicarbonate: A white, crystalline powder that is commonly used as a pH buffering agent, an electrolyte replenisher, systemic alkalizer and in topical cleansing solutions. [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] Soybean Oil: Oil from soybean or soybean plant. [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] Spondylitis: Inflammation of the vertebrae. [EU] Stabilization: The creation of a stable state. [EU] Statistically significant: Describes a mathematical measure of difference between groups. The difference is said to be statistically significant if it is greater than what might be expected to happen by chance alone. [NIH] Stent: A device placed in a body structure (such as a blood vessel or the gastrointestinal tract) to provide support and keep the structure open. [NIH] Sterility: 1. The inability to produce offspring, i.e., the inability to conceive (female s.) or to induce conception (male s.). 2. The state of being aseptic, or free from microorganisms. [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]
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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] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Sublingual: Located beneath the tongue. [EU] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]
Substrate: A substance upon which an enzyme acts. [EU] Suction: The removal of secretions, gas or fluid from hollow or tubular organs or cavities by means of a tube and a device that acts on negative pressure. [NIH] Superoxide: Derivative of molecular oxygen that can damage cells. [NIH] Superoxide Dismutase: An oxidoreductase that catalyzes the reaction between superoxide anions and hydrogen to yield molecular oxygen and hydrogen peroxide. The enzyme protects the cell against dangerous levels of superoxide. EC 1.15.1.1. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire body. [NIH] Systemic lupus erythematosus: SLE. A chronic inflammatory connective tissue disease marked by skin rashes, joint pain and swelling, inflammation of the kidneys, inflammation of the fibrous tissue surrounding the heart (i.e., the pericardium), as well as other problems. Not all affected individuals display all of these problems. May be referred to as lupus. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tacrolimus: A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro. [NIH] Teratogenic: Tending to produce anomalies of formation, or teratism (= anomaly of formation or development : condition of a monster). [EU] Testosterone: A hormone that promotes the development and maintenance of male sex
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characteristics. [NIH] Thalamic: Cell that reaches the lateral nucleus of amygdala. [NIH] Thalamic Diseases: Disorders of the centrally located thalamus, which integrates a wide range of cortical and subcortical information. Manifestations include sensory loss, movement disorders; ataxia, pain syndromes, visual disorders, a variety of neuropsychological conditions, and coma. Relatively common etiologies include cerebrovascular disorders; craniocerebral trauma; brain neoplasms; brain hypoxia; intracranial hemorrhages; and infectious processes. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thigh: A leg; in anatomy, any elongated process or part of a structure more or less comparable to a leg. [NIH] 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] Thrombolytic: 1. Dissolving or splitting up a thrombus. 2. A thrombolytic agent. [EU] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]
Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] Tin: A trace element that is required in bone formation. It has the atomic symbol Sn, atomic number 50, and atomic weight 118.71. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Culture: Maintaining or growing of tissue, organ primordia, or the whole or part of an organ in vitro so as to preserve its architecture and/or function (Dorland, 28th ed). Tissue culture includes both organ culture and cell culture. [NIH] Tissue Distribution: Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] 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] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] 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] Transaminase: Aminotransferase (= a subclass of enzymes of the transferase class that catalyse the transfer of an amino group from a donor (generally an amino acid) to an acceptor (generally 2-keto acid). Most of these enzymes are pyridoxal-phosphate-proteins. [EU]
Transcriptase: An enzyme which catalyses the synthesis of a complementary mRNA molecule from a DNA template in the presence of a mixture of the four ribonucleotides (ATP, UTP, GTP and CTP). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Translocation: The movement of material in solution inside the body of the plant. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Triglyceride: A lipid carried through the blood stream to tissues. Most of the body's fat tissue is in the form of triglycerides, stored for use as energy. Triglycerides are obtained primarily from fat in foods. [NIH] Troglitazone: A drug used in diabetes treatment that is being studied for its effect on reducing the risk of cancer cell growth in fat tissue. [NIH] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other
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mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] Tumour: 1. Swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. A new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU] 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] Ultrasonography: The visualization of deep structures of the body by recording the reflections of echoes of pulses of ultrasonic waves directed into the tissues. Use of ultrasound for imaging or diagnostic purposes employs frequencies ranging from 1.6 to 10 megahertz. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] 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] Uric: A kidney stone that may result from a diet high in animal protein. When the body breaks down this protein, uric acid levels rise and can form stones. [NIH] 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] Urticaria: A vascular reaction of the skin characterized by erythema and wheal formation due to localized increase of vascular permeability. The causative mechanism may be allergy, infection, or stress. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vascular endothelial growth factor: VEGF. A substance made by cells that stimulates new blood vessel formation. [NIH] Vasculitis: Inflammation of a blood vessel. [NIH] Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [NIH] Vasodilation: Physiological dilation of the blood vessels without anatomic change. For dilation with anatomic change, dilatation, pathologic or aneurysm (or specific aneurysm) is used. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU]
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Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vertebrae: A bony unit of the segmented spinal column. [NIH] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Virus Diseases: A general term for diseases produced by viruses. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Viscosity: A physical property of fluids that determines the internal resistance to shear forces. [EU] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]
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] Xanthoma: A tumour composed of lipid-laden foam cells, which are histiocytes containing cytoplasmic lipid material. Called also xanthelasma. [EU] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]
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INDEX A Abdominal, 151, 173, 177, 183, 184 Acceptor, 151, 177, 183, 195 Acetamides, 101, 151 Acetylcholine, 58, 151, 182 Acute leukemia, 5, 151 Acute renal, 59, 151 Acyl, 102, 151 Adaptability, 151, 159 Adipose Tissue, 151, 177 Adrenal Glands, 151, 153 Adrenal Medulla, 151, 159 Adrenergic, 151, 154 Adrenergic beta-Antagonists, 151, 154 Adverse Effect, 35, 151, 191 Aerosol, 111, 151 Affinity, 151, 177, 192 Agar, 152, 185 Age of Onset, 152, 196 Algorithms, 152, 157 Alkaline, 152, 158 Allograft, 152, 181 Alopecia, 20, 29, 70, 80, 152, 164 Alternative medicine, 127, 152 Aluminum, 104, 109, 152 Ameliorated, 14, 152 Amine, 152, 172 Amino Acid Sequence, 152, 153, 170 Amino Acids, 152, 168, 170, 183, 186, 188, 195, 196 Amlodipine, 43, 76, 84, 102, 103, 113, 119, 152 Amnestic, 152, 179 Amputation, 7, 10, 153 Amyloidosis, 12, 153 Analog, 153, 190 Anatomical, 153, 163, 165, 174, 191 Anesthesia, 153, 179 Aneurysm, 153, 170, 196 Angina, 8, 20, 32, 38, 43, 44, 57, 60, 72, 73, 103, 107, 113, 120, 151, 152, 153, 182 Angina Pectoris, 20, 32, 38, 43, 57, 60, 72, 103, 107, 113, 151, 152, 153 Angiography, 7, 153 Angioscopy, 30, 153 Angiotensin-Converting Enzyme Inhibitors, 153, 154 Animal model, 12, 102, 153
Anions, 153, 175, 193 Anomalies, 153, 193 Antagonism, 153, 165 Antibiotic, 153, 156, 160, 168 Antibodies, 28, 58, 153, 172, 178, 185 Antibody, 152, 153, 154, 161, 174, 178, 192 Anticoagulant, 154, 188 Antidote, 154, 158 Antigen, 25, 29, 70, 80, 152, 153, 154, 161, 172, 173, 174, 178 Antihypertensive, 107, 154 Antihypertensive Agents, 107, 154 Anti-inflammatory, 12, 20, 65, 154, 155, 171, 187, 190 Anti-Inflammatory Agents, 154, 155 Antineoplastic, 154, 164, 184 Antineoplastic Agents, 154, 184 Antioxidant, 119, 154, 155, 183 Antipruritic, 154, 160 Antiviral, 14, 154, 175, 181 Antiviral Agents, 14, 154 Anxiolytic, 154, 179 Aorta, 154, 173, 197 Aortic Valve, 69, 79, 154 Apheresis, 23, 24, 35, 51, 62, 75, 83, 91, 154 Apolipoproteins, 14, 154, 170, 177 Apoptosis, 11, 154 Approximate, 109, 155 Aqueous, 155, 156, 164, 167, 173, 176 Arginine, 155, 182 Arterial, 7, 8, 10, 12, 20, 30, 31, 35, 68, 78, 119, 155, 160, 173, 182, 188, 193 Arteries, 3, 6, 125, 136, 154, 155, 157, 159, 163, 173, 177, 179, 180 Arterioles, 155, 157, 159, 180 Arteriolosclerosis, 155 Arteriosclerosis, 25, 55, 58, 90, 105, 115, 155, 173 Ascorbic Acid, 8, 155, 173 Aspirin, 65, 112, 113, 119, 155 Assay, 36, 155 Asymptomatic, 57, 155, 183 Ataxia, 58, 155, 194 Atherogenic, 4, 14, 23, 33, 37, 42, 71, 80, 81, 102, 136, 155 Atrophy, 155, 177 Autodigestion, 155, 183 Autoimmune disease, 6, 77, 85, 155, 180
200 Atorvastatin
Autonomic, 38, 151, 155, 170 Azithromycin, 19, 156 B Bacteria, 151, 153, 154, 156, 160, 162, 167, 168, 172, 179, 196 Bactericidal, 156, 169 Bacteriophage, 156, 185 Bacteriostatic, 156, 168 Basal Ganglia, 155, 156 Basal Ganglia Diseases, 155, 156 Base, 8, 14, 101, 110, 156, 165, 170, 176, 196 Basophil, 29, 70, 80, 156, 172 Bezafibrate, 30, 38, 57, 72, 156 Bile, 109, 156, 160, 170, 177, 192 Bile Acids, 109, 156, 192 Bile Acids and Salts, 156 Biliary, 156, 160, 183 Biliary Tract, 156, 183 Bioavailability, 9, 106, 108, 109, 113, 115, 126, 156 Biochemical, 33, 42, 71, 80, 156, 191 Biological response modifier, 156, 175 Biological Transport, 156, 165 Biopsy, 16, 157 Biopterin, 157, 181 Biosynthesis, 5, 100, 101, 105, 108, 109, 110, 118, 157, 177, 181, 187, 191 Biotechnology, 17, 127, 135, 157 Biotransformation, 56, 157 Bladder, 157, 180, 196 Blasts, 5, 157 Blood Coagulation, 49, 157, 158, 194 Blood pressure, 13, 14, 43, 72, 81, 125, 154, 157, 159, 170, 173, 180, 184, 192 Blood vessel, 102, 153, 157, 158, 159, 160, 167, 168, 171, 175, 184, 185, 192, 193, 194, 196 Body Fluids, 157, 158, 181, 192 Body Mass Index, 157, 183 Bone Marrow, 151, 157, 164, 174, 178, 180 Bone Marrow Cells, 157, 180 Bowel, 157, 165, 184 Bowel Movement, 157, 165 Bradykinin, 157, 182 Branch, 147, 158, 167, 183, 188, 192, 194 Breakdown, 158, 165, 170, 191 Bronchi, 158 Bronchial, 158, 172 Bronchitis, 111, 158 Buccal, 5, 158, 177 Buccal mucosa, 5, 158 Bullous, 52, 158
Bypass, 10, 158 C Cadaver, 8, 158 Calcification, 14, 57, 155, 158 Calcineurin, 16, 158 Calcium Carbonate, 35, 106, 109, 158 Calcium channel blocker, 152, 154, 158 Calcium Channel Blockers, 154, 158 Calcium Chloride, 101, 158 Calcium Hydroxide, 101, 109, 110, 116, 159 Calmodulin, 158, 159 Capillary, 41, 157, 159, 170, 177, 197 Capsules, 106, 115, 159, 166, 170 Carbohydrates, 159, 160 Carcinogenic, 159, 174, 187, 192 Cardiac, 8, 43, 53, 56, 59, 103, 107, 113, 120, 151, 159, 163, 179, 180, 189, 192 Cardiorespiratory, 159, 179 Cardiovascular disease, 4, 6, 8, 13, 48, 100, 112, 113, 117, 120, 136, 159, 177 Carotid Arteries, 6, 159 Catabolism, 14, 159 Catalyse, 159, 195 Catecholamine, 9, 159 Catheters, 9, 159 Cause of Death, 111, 159 Cell Cycle, 90, 159 Cell Death, 118, 154, 159, 181 Cell Division, 156, 159, 160, 179, 185 Cell membrane, 109, 119, 156, 158, 159, 169, 185 Cell proliferation, 155, 160, 191 Central Nervous System, 77, 85, 151, 158, 160, 170, 180, 191 Centrifugation, 160, 179 Cerebellar, 155, 160, 189 Cerebral, 12, 155, 156, 160 Cerebrovascular, 113, 156, 158, 159, 160, 194 Cerebrum, 160 Character, 153, 160, 164 Chemoprevention, 11, 160 Cholesterol Esters, 160, 177 Cholestyramine, 32, 71, 80, 106, 160 Chromatin, 154, 160 Chronic, 16, 30, 35, 44, 55, 96, 111, 124, 154, 160, 166, 168, 174, 176, 183, 190, 193, 196 Chronic Disease, 111, 160 Chronic renal, 35, 44, 160, 196 Chylomicrons, 160, 177
Index 201
CIS, 104, 160 Citrus, 155, 160 Clarithromycin, 19, 37, 58, 160 Claudication, 8, 10, 123, 161 Clinical Medicine, 72, 91, 161, 186 Clinical study, 161, 163 Clinical trial, 3, 4, 5, 6, 8, 11, 13, 16, 90, 95, 97, 125, 135, 136, 161, 163, 164, 180, 188, 189 Cloning, 157, 161 Coagulation, 89, 157, 161, 194 Colestipol, 6, 161 Collagen, 8, 161, 185, 187 Combination Therapy, 15, 119, 161 Complement, 161, 162, 178 Complementary and alternative medicine, 89, 93, 162 Complementary medicine, 89, 162 Computational Biology, 135, 162 Computed tomography, 162 Computerized axial tomography, 162 Computerized tomography, 14, 162 Concomitant, 37, 58, 59, 76, 84, 119, 162 Conjugated, 156, 162, 164 Conjugation, 157, 162 Connective Tissue, 155, 157, 161, 163, 169, 170, 190, 193 Constriction, 163, 175, 196 Constriction, Pathologic, 163, 196 Consumption, 163, 182 Contamination, 163, 172 Contraindications, ii, 163 Control group, 163, 187 Controlled clinical trial, 11, 163 Controlled study, 24, 163 Coordination, 163, 180 Coronary Arteriosclerosis, 106, 163, 180 Coronary Circulation, 153, 163, 182 Coronary Disease, 51, 75, 83, 140, 163 Coronary heart disease, 4, 8, 33, 44, 45, 49, 57, 60, 64, 65, 73, 91, 109, 115, 125, 159, 163, 172 Coronary Thrombosis, 163, 179, 180 Coronary Vessels, 9, 163 Corpuscle, 163, 168 Cortex, 155, 163, 187, 189 Cortisone, 163, 187 Creatinine, 41, 164, 196 Cryptosporidiosis, 156, 164 Crystallization, 108, 115, 116, 164 Curative, 164, 182, 194 Cutaneous, 11, 164, 175, 177
Cyclic, 159, 164, 171, 182 Cyclophosphamide, 7, 164 Cyclosporine, 29, 58, 70, 76, 80, 84, 164 Cytochrome, 16, 64, 95, 164 Cytokine, 10, 164 Cytoplasm, 154, 159, 164, 171 D Dairy Products, 164, 190 Databases, Bibliographic, 135, 164 Decarboxylation, 164, 172 Degenerative, 119, 164, 172 Delavirdine, 59, 164, 182 Deletion, 154, 165 Dendritic, 165, 178 Depressive Disorder, 165, 177 Dermatologist, 11, 165 Dermatology, 11, 52, 165 Dermatosis, 52, 165 Deuterium, 165, 173 Diabetes Mellitus, 4, 14, 33, 71, 80, 165, 171, 172 Diagnostic procedure, 99, 127, 165 Dialyzer, 165, 171 Diarrhea, 160, 164, 165 Diastolic, 165, 173 Dietary Fats, 165, 176 Diffusion, 116, 156, 165 Digestion, 156, 157, 165, 176, 177, 193 Digestive system, 97, 165 Dihydrotestosterone, 165, 189 Dihydroxy, 101, 103, 104, 108, 110, 114, 115, 120, 165 Dilatation, 153, 165, 187, 196 Dilatation, Pathologic, 165, 196 Dilation, 157, 165, 196 Dilator, 165, 182 Diltiazem, 59, 76, 84, 165 Direct, iii, 129, 161, 165, 189 Disease Progression, 8, 166 Disinfectant, 166, 169 Disposition, 15, 52, 64, 166 Diuretic, 29, 158, 166 Diuretics, Thiazide, 154, 166 Dosage Forms, 100, 166 Dose-dependent, 23, 37, 71, 81, 166 Drug Interactions, 15, 16, 46, 130, 166 Drug Resistance, 15, 166 Drug Tolerance, 166, 194 Duodenum, 156, 166, 167, 193 Dyslipidemia, 3, 22, 23, 26, 27, 33, 35, 42, 47, 48, 59, 62, 70, 91, 119, 136, 166
202 Atorvastatin
E Edema, 166, 181, 196 Effector, 151, 161, 166 Elasticity, 125, 155, 163, 166 Elastin, 161, 166 Elective, 8, 167 Electrocoagulation, 161, 167 Electrolyte, 16, 167, 186, 192, 196 Electrons, 154, 156, 167, 175, 178, 183, 188 Elementary Particles, 167, 178, 188 Embolus, 167, 174 Emergency Medicine, 119, 167 Emergency Treatment, 167 Emphysema, 111, 167 Emulsions, 23, 152, 167 Encephalitis, 167 Encephalomyelitis, 65, 167 Endocrine Glands, 167 Endopeptidases, 167, 187 Endoscopic, 153, 167, 179 Endothelial cell, 9, 39, 57, 68, 77, 167, 194 Endothelium, 4, 10, 12, 22, 24, 40, 55, 72, 102, 136, 168, 182, 185 Endothelium, Lymphatic, 168 Endothelium, Vascular, 168 Endothelium-derived, 168, 182 Endotoxic, 168, 176 Endotoxin, 168, 196 End-stage renal, 160, 168 Environmental Health, 134, 136, 168 Enzymatic, 158, 162, 168, 169, 172 Enzyme Inhibitors, 109, 168 Epidemiological, 12, 168 Epidermal, 64, 168, 178 Epidermis, 168 Epithelium, 168 Erythema, 168, 196 Erythrocyte Membrane, 62, 168 Erythromycin, 95, 156, 160, 168 Esophagus, 165, 168, 193 Ethanol, 100, 168, 169 Ether, 108, 169 Ethnic Groups, 13, 169 Exfoliation, 169, 181 Exocytosis, 169, 172 Exogenous, 25, 157, 169, 187, 196 Extracellular, 163, 169, 192 Extremity, 7, 10, 169 F Family Planning, 135, 169 Farnesyl, 5, 169
Fat, 14, 102, 151, 156, 157, 163, 167, 169, 176, 177, 180, 182, 183, 186, 190, 195 Fatty acids, 14, 70, 79, 100, 169 Femoral, 8, 169 Femoral Artery, 8, 169 Femur, 169 Fermentation, 117, 169 Fibrin, 157, 169, 185, 194 Fibrinogen, 37, 40, 48, 51, 54, 62, 75, 83, 169, 185, 194 Fibrinolytic, 46, 73, 81, 124, 169 Fibrosis, 111, 169, 191 Filtration, 115, 169 Foam Cells, 169, 197 Forearm, 157, 169 Fructose, 70, 79, 169, 175 G Gallbladder, 151, 156, 165, 170 Ganglia, 151, 156, 170, 181 Ganglionic Blockers, 154, 170 Gas, 165, 170, 173, 182, 193 Gastric, 155, 166, 170, 172 Gastrointestinal, 109, 157, 168, 170, 191, 192, 193 Gastrointestinal tract, 109, 168, 170, 191, 192 Gemfibrozil, 11, 14, 16, 47, 58, 102, 170 Gene, 13, 14, 31, 75, 82, 110, 157, 170, 173, 176 Gene Expression, 14, 75, 82, 170 Genetic Code, 170, 182 Genetic testing, 110, 170 Genetics, 13, 16, 162, 170 Genomics, 13, 170 Genotype, 14, 20, 30, 170, 184 Gland, 151, 163, 170, 183, 191 Glomerular, 16, 170, 175, 189 Glomerular Filtration Rate, 16, 170 Glomerulus, 170, 171, 181 Glucocorticoid, 171, 187 Glucose, 10, 14, 26, 59, 155, 165, 171, 175, 190 Glucose Intolerance, 165, 171 Glucuronic Acid, 171, 172 Glycoprotein, 90, 169, 171, 184, 194, 195 Gonadal, 171, 192 Governing Board, 171, 186 Graft, 8, 10, 171 Grafting, 171, 174 Granulocytes, 156, 171, 191, 197 Growth, 9, 11, 153, 155, 156, 157, 159, 160, 171, 175, 178, 182, 185, 195, 196
Index 203
Guanylate Cyclase, 171, 182 H Haplotypes, 13, 171 Heart attack, 29, 95, 118, 159, 171 Heart Transplantation, 46, 52, 59, 171 Heme, 164, 171 Hemodialysis, 22, 158, 165, 171 Hemoglobin, 171, 176 Hemolysis, 168, 172 Hemorrhage, 167, 172, 193 Heparin, 42, 172 Hepatic, 23, 49, 95, 124, 172, 191 Hepatitis, 19, 28, 172 Hepatitis A, 19, 172 Hepatocytes, 172 Hepatovirus, 172 Heredity, 170, 172 High-density lipoproteins, 102, 172 Histamine, 21, 29, 70, 80, 172 Histamine Release, 29, 70, 80, 172 Histidine, 172 Homogeneous, 117, 155, 172, 184 Hormone, 163, 172, 175, 187, 190, 191, 193 Hydrogen, 109, 151, 152, 156, 159, 165, 172, 173, 176, 180, 183, 188, 193 Hydrogen Peroxide, 173, 176, 193 Hydrolysis, 101, 110, 113, 157, 173, 186, 188 Hydrophobic, 173, 177 Hydroxylysine, 161, 173 Hydroxyproline, 161, 173 Hyperlipidaemia, 26, 27, 29, 44, 106, 173 Hyperlipoproteinemia, 25, 27, 40, 44, 45, 117, 173, 177 Hyperplasia, 41, 173 Hypersensitivity, 173, 190 Hypertension, 16, 43, 65, 73, 103, 107, 113, 119, 151, 152, 153, 154, 155, 158, 159, 173, 196 Hypertriglyceridemia, 14, 52, 55, 91, 166, 173 Hypertrophy, 173 Hypnotic, 173, 179 Hypolipidemic, 61, 104, 114, 173 Hypotensive, 76, 84, 173 I Id, 86, 91, 140, 146, 148, 173 Iliac Artery, 169, 173 Immune function, 38, 173 Immune response, 154, 155, 163, 173, 174, 178, 193, 197
Immune system, 173, 174, 178, 180, 181, 196, 197 Immunity, 174, 182 Immunization, 174, 187 Immunogenic, 174, 176 Immunophilin, 158, 174 Immunosuppressive, 158, 164, 171, 174, 193 Impairment, 27, 96, 155, 174, 179 Implantation, 37, 72, 81, 174 In vitro, 9, 12, 174, 193, 194 In vivo, 6, 9, 12, 16, 22, 23, 43, 72, 81, 172, 174, 193 Incision, 174, 175 Indicative, 174, 183, 196 Induction, 75, 82, 170, 174, 191 Infantile, 174, 177 Infarction, 112, 113, 174 Infection, 36, 91, 156, 164, 167, 173, 174, 178, 190, 193, 195, 196, 197 Infusion, 14, 174 Inhalation, 151, 174, 186 Initiation, 56, 174 Innervation, 174, 182 Inorganic, 175, 178 Insulator, 175, 180 Insulin, 10, 14, 59, 92, 105, 175, 176, 190, 196 Insulin-dependent diabetes mellitus, 175 Interferon, 26, 175 Interferon-alpha, 175 Interindividual, 13, 175 Intermittent, 8, 10, 175, 184 Internal Medicine, 45, 46, 70, 71, 73, 74, 76, 80, 81, 82, 84, 175, 181 Interstitial, 9, 111, 175, 181, 189 Intestines, 151, 160, 170, 175 Intoxication, 175, 197 Intracellular, 14, 158, 174, 175, 182, 186, 191 Intravenous, 63, 174, 175 Inulin, 170, 175 Invasive, 8, 174, 175, 178 Involuntary, 156, 175, 180 Ions, 156, 159, 160, 166, 167, 173, 175 Irritants, 151, 175 Ischemia, 8, 9, 10, 38, 155, 175 Islet, 7, 176 Isopropyl, 120, 121, 176 J Joint, 121, 176, 193
204 Atorvastatin
K Kb, 134, 176 Keto, 176, 195 Kidney Disease, 16, 18, 96, 97, 124, 134, 140, 176 Kidney stone, 176, 196 Kinetics, 36, 176 L Labile, 113, 161, 176 Large Intestine, 165, 175, 176, 189 Latent, 176, 187 Lens, 176, 189 Lethal, 111, 156, 176 Leucine, 14, 176 Leukapheresis, 154, 176 Leukemia, 5, 176, 180 Leukocytes, 157, 171, 175, 176, 196 Library Services, 146, 176 Ligaments, 163, 176 Lipaemia, 62, 76, 84, 176 Lipase, 23, 124, 176 Lipid A, 6, 120, 176 Lipid Peroxidation, 119, 176, 183 Lipodystrophy, 14, 177 Lipophilic, 16, 177 Lipopolysaccharides, 176, 177 Lipoprotein Lipase, 42, 75, 82, 110, 177 Lipoprotein(a), 14, 24, 62, 177 Lithium, 104, 177 Liver, 4, 16, 70, 79, 95, 100, 107, 151, 153, 156, 164, 165, 170, 171, 172, 177, 187, 189 Localized, 153, 174, 177, 185, 191, 196 Longitudinal Studies, 6, 177 Lubricants, 117, 177 Lung metastases, 11, 177 Lupus, 6, 13, 177, 193 Lupus Nephritis, 6, 177 Lymph, 163, 167, 168, 177, 178 Lymphatic, 168, 174, 177, 178, 192 Lymphocyte, 154, 178 Lymphoid, 153, 178 M Macrophage, 10, 12, 178 Magnesium Hydroxide, 109, 178 Magnetic Resonance Imaging, 7, 10, 178 Magnetic Resonance Spectroscopy, 16, 178 Maintenance therapy, 7, 35, 178 Major Histocompatibility Complex, 171, 178 Malignant, 5, 11, 154, 155, 178, 181 Mammary, 177, 178
Mammogram, 158, 178, 179 Manic, 177, 178 Meat, 105, 165, 178, 190 Medial, 20, 68, 78, 155, 178 Mediator, 8, 9, 178, 191 MEDLINE, 135, 178 Melanocytes, 11, 178, 179 Melanoma, 11, 179 Melanosomes, 178, 179 Membrane, 119, 159, 162, 165, 169, 179, 180, 182, 185, 186, 191, 195 Meninges, 160, 179 Menopause, 179, 186 Mental Disorders, 97, 179, 187, 188 Mental Health, iv, 4, 97, 134, 137, 179, 187, 188 Metabolite, 13, 15, 119, 157, 177, 179, 186, 187, 189 Methanol, 101, 179 MI, 36, 45, 62, 69, 79, 102, 104, 108, 113, 114, 124, 149, 179 Microbe, 179, 195 Microcalcifications, 158, 179 Microorganism, 179, 197 Microsomal, 14, 179 Microspheres, 9, 179 Midazolam, 63, 179 Migration, 11, 179 Mineralization, 159, 179 Mitosis, 155, 179 Modeling, 14, 19, 68, 77, 179 Modification, 5, 119, 180, 188 Molecular, 16, 43, 77, 85, 111, 119, 135, 137, 157, 158, 159, 162, 169, 172, 180, 185, 193, 196 Molecule, 154, 156, 161, 166, 168, 173, 180, 183, 189, 191, 195 Monitor, 164, 180, 182 Monocyte, 22, 180 Mononuclear, 26, 180, 196 Monotherapy, 15, 124, 180 Morphological, 178, 180 Morphology, 7, 30, 180 Mucosa, 177, 180 Multicenter study, 11, 16, 180 Multidrug resistance, 180, 184 Multiple sclerosis, 119, 180 Myelin, 180 Myelodysplasia, 5, 180 Myelogenous, 180
Index 205
Myocardial infarction, 7, 8, 20, 38, 43, 44, 57, 60, 72, 73, 76, 84, 105, 112, 113, 163, 179, 180 Myocardial Ischemia, 9, 32, 43, 44, 50, 57, 73, 153, 163, 180 Myocardium, 9, 153, 179, 180 Myopathy, 5, 16, 180 Myosin, 158, 180 N Nausea, 166, 181, 196 NCI, 1, 97, 133, 160, 181 Necrolysis, 64, 181 Necrosis, 154, 174, 179, 180, 181, 189 Need, 3, 7, 8, 114, 115, 136, 141, 160, 181, 194 Nelfinavir, 15, 17, 55, 181 Neopterin, 26, 181 Nephritis, 7, 181 Nephrology, 17, 22, 23, 44, 46, 60, 65, 96, 181 Nephropathy, 176, 181 Nephrosis, 181 Nephrotic, 16, 96, 181 Nephrotic Syndrome, 96, 181 Nerve, 151, 153, 155, 163, 174, 178, 180, 181, 191, 195 Nervous System, 153, 160, 178, 181, 193 Neural, 19, 68, 77, 170, 181 Neuromuscular, 151, 181, 182, 196 Neuromuscular Junction, 151, 181, 182 Neuronal, 12, 181 Neurons, 170, 181 Neurotoxicity, 12, 181 Neurotoxin, 119, 181 Niacin, 6, 33, 42, 71, 80, 86, 118, 181, 195 Nitric Oxide, 9, 12, 45, 119, 182 Nitrogen, 152, 164, 182, 195 Nitroglycerin, 118, 182 Non-nucleoside, 164, 182 Nuclear, 70, 156, 162, 167, 181, 182 Nuclei, 162, 167, 178, 179, 182, 188 Nucleic acid, 110, 170, 182 Nucleus, 154, 156, 160, 164, 165, 167, 180, 182, 188, 194 Nutritional Status, 14, 182 O Ocular, 182 Ointments, 166, 182 Omega-3 fatty acid, 72, 89, 90, 91, 182 Opacity, 165, 182 Ophthalmoplegia, 58, 182 Organ Culture, 182, 194
Organelles, 160, 164, 178, 179, 182 Overweight, 62, 76, 84, 85, 183 Oxidation, 40, 43, 72, 81, 151, 154, 157, 164, 176, 183 Oxidation-Reduction, 157, 183 Oxidative Stress, 9, 183 P Palliative, 183, 194 Pancreas, 19, 151, 165, 175, 176, 183 Pancreatic, 183 Pancreatitis, 14, 19, 183 Paralysis, 7, 65, 77, 85, 182, 183 Paroxysmal, 153, 183 Partial remission, 16, 183, 189 Partial response, 183 Particle, 26, 33, 71, 80, 100, 108, 109, 112, 117, 183 Pathogenesis, 9, 12, 14, 183 Pathologic, 155, 157, 163, 173, 183 Pathologic Processes, 155, 183 Peptide, 161, 167, 183, 184, 186, 187, 188 Peptide Chain Elongation, 161, 184 Perfusion, 9, 184, 194 Perioperative, 8, 184 Peripheral blood, 26, 175, 184 Peripheral Vascular Disease, 5, 35, 63, 184 Peritoneal, 18, 184 Peritoneal Cavity, 184 Peritoneal Dialysis, 18, 184 Peritoneum, 184 Peroral, 106, 184 P-Glycoprotein, 16, 184 Pharmaceutical Solutions, 166, 184 Pharmacodynamic, 5, 16, 19, 55, 68, 77, 184 Pharmacokinetic, 16, 17, 29, 55, 70, 80, 184 Pharmacologic, 153, 184, 194, 195 Phenotype, 39, 184 Phenyl, 101, 102, 104, 108, 110, 114, 115, 184 Phospholipids, 169, 177, 184 Phosphorus, 158, 185 Phosphorylated, 161, 185 Photocoagulation, 161, 185 Physiologic, 157, 175, 185, 189 Physiology, 68, 70, 77, 159, 181, 185 Pigment, 178, 179, 185 Pilot study, 6, 25, 62, 63, 185 Plants, 160, 171, 175, 180, 185, 186, 190, 195 Plaque, 6, 7, 22, 30, 43, 55, 61, 75, 76, 83, 84, 119, 123, 155, 185
206 Atorvastatin
Plasma cells, 153, 185 Plasmapheresis, 154, 185 Plasmin, 185 Plasminogen, 39, 41, 63, 185 Plasminogen Activators, 185 Platelet Aggregation, 22, 26, 118, 182, 185 Plateletpheresis, 154, 186 Platelets, 69, 78, 102, 118, 182, 185, 186, 191, 194 Pneumonitis, 111, 186 Poisoning, 158, 175, 181, 186 Polymerase, 154, 186 Polymorphic, 100, 107, 112, 186 Polypeptide, 152, 161, 169, 185, 186, 197 Polysaccharide, 154, 186 Polyunsaturated fat, 119, 186 Posterior, 155, 183, 186 Postmenopausal, 40, 72, 186 Postoperative, 8, 186 Postoperative Period, 8, 186 Postprandial, 24, 25, 44, 62, 69, 72, 73, 76, 79, 84, 90, 186 Post-translational, 5, 186 Potassium, 29, 166, 186 Practice Guidelines, 137, 186 Preclinical, 5, 110, 186 Precursor, 101, 108, 109, 110, 119, 164, 166, 168, 169, 181, 185, 186, 187, 195 Predisposition, 110, 187 Prednisolone, 187 Prednisone, 16, 187 Prevalence, 12, 187 Primary endpoint, 8, 187 Primary Prevention, 34, 71, 187 Probe, 125, 187 Prodrug, 187, 189 Progesterone, 187, 192 Progression, 7, 10, 12, 16, 18, 41, 96, 124, 153, 187 Progressive, 37, 71, 81, 155, 160, 166, 171, 181, 187, 189, 196 Proline, 161, 173, 187 Promoter, 23, 187 Prophylaxis, 105, 154, 187, 189 Prospective study, 18, 187 Protease, 11, 14, 15, 161, 181, 187, 190 Protease Inhibitors, 11, 14, 15, 187 Protein Binding, 187, 194 Protein C, 38, 152, 154, 156, 177, 187 Protein S, 154, 157, 160, 168, 170, 188 Proteins, 5, 152, 154, 160, 161, 168, 180, 182, 183, 185, 187, 188, 191, 195
Proteinuria, 16, 18, 96, 181, 188 Proteolytic, 161, 169, 185, 188 Protocol, 6, 10, 188 Protons, 173, 178, 188 Psychiatric, 12, 96, 179, 188 Psychiatry, 188 Public Health, 11, 137, 188 Public Policy, 135, 188 Publishing, 17, 188 Pulmonary, 111, 157, 163, 188, 197 Pulmonary Artery, 157, 188, 197 Pulse, 43, 73, 180, 188 Purifying, 116, 188 Pyridoxal, 188, 195 Q Quality of Life, 10, 111, 188 R Race, 8, 104, 179, 188 Radiation, 153, 167, 188, 189, 197 Radioactive, 173, 174, 182, 189 Ramipril, 13, 189 Randomized clinical trial, 18, 57, 189 Receptor, 14, 39, 58, 70, 79, 100, 111, 154, 189, 191 Rectum, 157, 165, 170, 176, 189 Recurrence, 160, 189 Red Nucleus, 155, 189 Refer, 1, 158, 161, 189 Refractory, 16, 167, 189 Regimen, 15, 95, 166, 189 Remission, 178, 189 Renal failure, 22, 189 Resolving, 42, 189 Respiratory distress syndrome, 111, 189 Resuscitation, 167, 189 Retinoids, 189 Retinol, 87, 189 Rhabdomyolysis, 16, 19, 37, 58, 59, 76, 84, 189 Rheology, 23, 190 Rheumatism, 190 Rheumatoid, 7, 121, 190 Rheumatoid arthritis, 7, 121, 190 Risk factor, 33, 48, 64, 71, 80, 105, 115, 187, 190 Risk patient, 48, 74, 119, 190 Ritonavir, 11, 14, 15, 37, 91, 190 Rosiglitazone, 10, 45, 73, 81, 190 S Salicylate, 19, 190 Salivary, 165, 190 Salivary glands, 165, 190
Index 207
Saponins, 190, 192 Saquinavir, 11, 15, 190 Saturated fat, 14, 190 Schizoid, 190, 197 Schizophrenia, 190, 197 Schizotypal Personality Disorder, 190, 197 Scleroderma, 7, 155, 190 Sclerosis, 155, 180, 191 Screening, 161, 191 Secretion, 14, 56, 172, 175, 191 Sedative, 179, 191 Semisynthetic, 160, 191 Senescence, 90, 191 Serotonin, 191, 195 Serous, 168, 191 Side effect, 11, 112, 113, 121, 129, 151, 164, 191, 195 Signal Transduction, 158, 191 Signs and Symptoms, 7, 189, 191, 196 Skeletal, 10, 189, 191 Skeleton, 169, 176, 191 Smooth muscle, 9, 70, 75, 83, 158, 169, 172, 182, 192, 193 Social Environment, 188, 192 Sodium, 101, 109, 166, 192 Sodium Bicarbonate, 109, 192 Solvent, 103, 104, 114, 115, 116, 169, 179, 184, 192 Soybean Oil, 186, 192 Specialist, 141, 165, 192 Species, 117, 179, 188, 192, 193, 195, 197 Specificity, 152, 167, 192, 194 Spinal cord, 160, 167, 179, 181, 192 Spleen, 153, 178, 192 Spondylitis, 7, 192 Stabilization, 8, 55, 75, 83, 118, 192 Statistically significant, 11, 192 Stent, 37, 72, 81, 192 Sterility, 164, 192 Steroid, 109, 156, 163, 190, 191, 192 Stimulant, 172, 192 Stomach, 151, 155, 165, 168, 170, 172, 175, 181, 184, 192, 193 Stress, 8, 9, 159, 181, 183, 187, 190, 193, 196 Stroke, 7, 8, 44, 56, 73, 75, 83, 97, 119, 124, 134, 159, 193 Subacute, 174, 193 Subclinical, 34, 71, 174, 193 Subcutaneous, 166, 177, 193 Sublingual, 118, 193 Subspecies, 25, 69, 79, 192, 193 Substance P, 168, 179, 191, 193
Substrate, 168, 193 Suction, 169, 193 Superoxide, 9, 193 Superoxide Dismutase, 9, 193 Supplementation, 14, 193 Suppression, 118, 193 Symptomatic, 10, 183, 193 Synergistic, 105, 107, 119, 193 Systemic, 9, 12, 61, 111, 130, 153, 154, 157, 174, 177, 187, 191, 192, 193 Systemic lupus erythematosus, 12, 177, 193 Systolic, 9, 173, 193 T Tacrolimus, 16, 193 Teratogenic, 11, 165, 193 Testosterone, 189, 193 Thalamic, 155, 194 Thalamic Diseases, 155, 194 Therapeutics, 18, 19, 31, 35, 39, 42, 45, 47, 48, 51, 54, 55, 64, 100, 111, 112, 117, 130, 194 Thigh, 169, 194 Threshold, 173, 194 Thrombin, 169, 185, 188, 194 Thrombocytes, 186, 194 Thrombolytic, 185, 194 Thrombomodulin, 188, 194 Thrombosis, 22, 25, 45, 49, 55, 58, 61, 89, 90, 95, 100, 112, 117, 188, 193, 194 Thrombus, 118, 163, 174, 180, 185, 194 Tin, 75, 83, 194 Tissue Culture, 11, 194 Tissue Distribution, 16, 194 Tolerance, 7, 64, 151, 171, 194 Tomography, 10, 34, 71, 178, 194 Topical, 169, 173, 192, 194 Torsion, 174, 195 Toxic, iv, 64, 119, 162, 167, 174, 179, 195 Toxicity, 16, 110, 166, 195 Toxicology, 69, 79, 136, 195 Toxins, 154, 167, 171, 174, 195 Toxoplasmosis, 156, 195 Trace element, 194, 195 Transaminase, 5, 195 Transcriptase, 164, 182, 195 Transfection, 157, 195 Translation, 168, 195 Translational, 195 Translocation, 160, 168, 195 Transmitter, 151, 178, 195
208 Atorvastatin
Transplantation, 7, 23, 26, 28, 29, 44, 46, 52, 59, 60, 70, 79, 160, 174, 178, 195 Trauma, 156, 181, 183, 194, 195 Triglyceride, 4, 14, 16, 18, 23, 25, 50, 52, 56, 69, 70, 75, 79, 82, 161, 173, 195 Troglitazone, 4, 55, 105, 195 Tryptophan, 26, 161, 191, 195 Tuberculosis, 163, 177, 195 Tumor Necrosis Factor, 39, 121, 195 Tumour, 196, 197 Type 2 diabetes, 3, 19, 22, 23, 24, 26, 31, 36, 45, 61, 62, 68, 69, 73, 78, 81, 124, 136, 196 U Ultrasonography, 10, 196 Unconscious, 173, 196 Uraemia, 183, 196 Uremia, 189, 196 Uric, 41, 196 Urine, 157, 164, 166, 176, 188, 196 Urticaria, 30, 196 V Vaccine, 188, 196 Vascular endothelial growth factor, 9, 22, 196 Vasculitis, 183, 196 Vasoconstriction, 118, 196 Vasodilation, 4, 10, 12, 24, 40, 55, 72, 118, 136, 153, 196
Vasodilator, 154, 157, 172, 196 Vein, 10, 11, 153, 175, 182, 196 Venous, 9, 182, 188, 196 Ventricle, 154, 188, 193, 197 Venules, 157, 159, 168, 197 Vertebrae, 192, 197 Vesicular, 179, 197 Veterinary Medicine, 135, 197 Viral, 154, 167, 181, 197 Virulence, 195, 197 Virus, 154, 156, 175, 185, 197 Virus Diseases, 154, 197 Visceral, 38, 39, 48, 72, 74, 82, 184, 197 Viscosity, 190, 197 Vitro, 5, 172, 197 Vivo, 6, 197 W White blood cell, 153, 156, 176, 178, 180, 185, 197 Withdrawal, 56, 197 X Xanthoma, 105, 197 Xenograft, 153, 197 X-ray, 119, 162, 178, 182, 197 Y Yeasts, 184, 197 Z Zymogen, 187, 197
Index 209
210 Atorvastatin
Index 211
212 Atorvastatin
